Synthesis of 12 Stereochemically and Structurally Diverse C-Trisaccharides

Article abstract of DOI:10.1021/jo9621534

Cell surface carbohydrates and their analogs may be used to study the cellular interactions responsible for adhesion to pathogenic bacteria, viruses, and other cells and may represent leads for drug discovery. We have generated 12 C-trisaccharides (7-18) as potential inhibitors for the cell surface proteins of the bacterium Helicobactor pylori. The strategy used has resulted in the generation of C-trisaccharides structures that are represented by the formula Fuc-α(1-2)-hexose-(1-3)-GlcNAc where each of the 12 compounds possesses a central sugar that has been systematically replaced with stereochemically diverse structures, including D and L sugars, through de novo synthesis. This aroach relies upon an organometallic coupling of terminal monosaccharides 19 and 20 to prepare a "disaccharide" in a convergent manner. This intermediate is then divergently derivatized to form a variety of structural analogs about the central hexose. For the separable compounds, the assignment of stereochemistry was done using standard NMR techniques. In cases where inseparable diastereomeric mixtures were generated, we have described a novel recursive stereochemical deconvolution strategy. This recursive strategy is demonstrated in the diastereoselective synthesis of trisaccharides 14, subsequent to its initial rapid synthesis as a component of a diastereomeric mixture. Biological assays of these compounds should provide an insight into the binding requirements of carbohydrate receptors.

Full text of DOI:10.1021/jo9621534

J . Org. Chem. 1997, 62, 5267-5283
5267
Syn th esis of 12 Ster eoch em ica lly a n d Str u ctu r a lly Diver se
C-Tr isa cch a r id es
Daniel P. Sutherlin and Robert W. Armstrong*
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095
Received November 18, 1996X
Cell surface carbohydrates and their analogs may be used to study the cellular interactions
responsible for adhesion to pathogenic bacteria, viruses, and other cells and may represent leads
for drug discovery. We have generated 12 C-trisaccharides (7-18) as potential inhibitors for the
cell surface proteins of the bacterium Helicobactor pylori. The strategy used has resulted in the
generation of C-trisaccharides structures that are represented by the formula Fuc-R(1-2)-hexose-
(1-3)-GlcNAc where each of the 12 compounds possesses a central sugar that has been systematically
replaced with stereochemically diverse structures, including D and L sugars, through de novo
synthesis. This approach relies upon an organometallic coupling of terminal monosaccharides 19
and 20 to prepare a “disaccharide” in a convergent manner. This intermediate is then divergently
derivatized to form a variety of structural analogs about the central hexose. For the separable
compounds, the assignment of stereochemistry was done using standard NMR techniques. In cases
where inseparable diastereomeric mixtures were generated, we have described a novel recursive
stereochemical deconvolution strategy. This recursive strategy is demonstrated in the diastereo-
selective synthesis of trisaccharides 14, subsequent to its initial rapid synthesis as a component of
a diastereomeric mixture. Biological assays of these compounds should provide an insight into
the binding requirements of carbohydrate receptors.
In tr od u ction
condensation6 as well as a synthesis of stereochemically
diverse C-disaccharides7 and C-trisaccharides8 through
solution phase chemistry, thereby generating these sug-
ars partially de novo, i.e., from non-carbohydrate starting
materials. In this paper we wish to elaborate on the
approach we developed for the synthesis of 12 C-trisac-
charide glycomimetics of the H type I blood group
determinant 1 having a general stucture 2 which pos-
sesses a diverse core hexose (Figure 1). We also describe
the rationale behind the development of chemical steps
which alow for the identification of unknown structures
through a recursive stereochemical deconvolution.
Oligosaccharides on the surface of cells are responsible
for many cell-cell recognition events in biological sys-
tems. These oligosaccharides are bound by receptor
proteins found on the surface of various other cells,
leading to adhesion.1 The biological consequences of
these events can be beneficial as in fertilization or
detrimental as in bacterial2 or viral adhesion,3 metasta-
sis,4 and inflammation.5 The development of compounds
that can interrupt this process by preferentially binding
to the receptors of specific carbohydrates or that can be
used as molecular probes of these receptors has clear
therapeutic value and has been the impetus behind the
recent increase in activity in this field of research.
Ba ck gr ou n d
There has been interest in translating the successes
of combinatorial chemistry9 onto carbohydrates. How-
ever, addressing the issues of carbohydrate diversity is
a daunting task. Oligosaccharides derive their diversity
from connectivity and stereochemistry. When these two
factors are considered in a calculation of possible dia-
stereomers of a hexose disaccharide, one arrives at over
5000 possible structures, as compared to the 8 possible
diastereomers of a peptide dimer.10 This, along with the
lack of efficient, stereoselective coupling strategies, the
high cost of uncommon hexoses (i.e., idose and altrose),
and the need for selectively protected alcohols has limited
the ability to treat sugars in a manner similar to that of
peptides. As a consequence, the application of small
Our desire has been to develop synthetic strategies that
will yield structurally diverse glycomimetics which may
be used to examine the carbohydrate-protein interac-
tions at the molecular level. To this end, we have
demonstrated a combinatorial approach to C-glycopeptide
ligands on solid support using the Ugi four-component
X Abstract published in Advance ACS Abstracts, J uly 1, 1997.
(1) (a) Varki, A. Glycobiology 1993, 3, 97-130. (b) Feizi, T. Curr.
Opin. Struct. Bio. 1993, 3, 701. (c) Varki, A. Proc. Natl. Acad. Sci.
U.S.A. 1994, 91, 7390. (d) Opdenakker, G.; Rudd, P. M.; Ponting, C.
P.; Dwek, R. FASEB J . 1993, 7, 1330.
(2) (a) Gyler, M.; Rose, D.; Bundle, D. Science 1991, 253, 442. (b)
Boren, T.; Falk, P.; Roth, K. A.; Larson, G.; Normark, S. Science 1993,
262, 1892.
(3) (a) Paulson, J . C. The Receptors; Academic: New York, 1985;
Vol. 2. (b) Wharton, S. A.; Weis, W.; Skehel, J . J .; Wiley, D. C. The
Influenza Virus; Plenum: New York, 1989.
(4) (a) Phillips, M. L.; Nudelman, E.; Gaeta, F. C. A.; Perez, M.;
Sinhal, A. K.; Hakomori, S.; Paulson, J . C. Science 1990, 250, 1130.
(b) Higashi, H.; Hirabayashi, Y.; Fukui, Y.; Naiki, M.; Matsumoto, M.;
Ueda, S.; Kato, S. Cancer Res. 1985, 45, 3796-3802. (c) Muramatsu,
T. Glycobiology 1993, 3, 298. (d) Hiraizumi, S.; Takasaki, S.; Ohuchi,
N.; Harada, Y.; Nose, M.; Mori, S.; Kobata, A. J . Cancer Res. 1992,
83, 1063.
(6) Sutherlin, D. P.; Hughes R.; Stark, T. M.; Armstrong, R. W. J .
Org. Chem. 1996, 61, 8350.
(7) Armstrong, R. W.; Sutherlin, D. P. Tetrahedron Lett. 1994, 35,
7743.
(8) Sutherlin, D. P.; Armstrong, R. W. J . Am. Chem. Soc. 1996, 118,
9802.
(9) (a) Gallop, M. A.; Barrett, R. W.; Dower, W. J .; Fodor, S. P. A.;
Gordon, E. M. J . Med. Chem. 1994, 37, 1233-1251. (b) Gordon, E. M.;
Barrett, R. W.; Dower, W. J .; Fodor, S. P. A.; Gallop, M. A. J . Med.
Chem. 1994, 37, 1385-1401.
(10) While only a fraction of the 5000 possible disaccharides occur
in nature, the diversity pool nonetheless is of great interest.
(5) (a) Butcher, E. C. Am. J . Path. 1990, 1, 3-11. (b) Walz, G.;
Aruffo, A.; Kolanus, W.; Polley, M. J .; Phillips, M. L.; Wagner, E.;
Nudelman, E.; Sinhal, A. K.; Hakomori, S.; Paulson, J . C. Proc. Natl.
Acad. Sci. U.S.A. 1991, 88, 6224.
S0022-3263(96)02153-6 CCC: $14.00 © 1997 American Chemical Society

5268 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
F igu r e 1. Retrosynthetic analysis of C-glycoside mimetics.
molecule combinatorial chemistry approaches11 may be
better suited to tackling many of the challenges that are
presented by this ubiquitous class of molecules.12
to be well suited for library generation. Conceptually,
this method differs from the others in that the sugars
are extended at the reducing end rather than through
glycosylations onto polymer bound carbohydrates. These
types of methods have thus far yielded the largest
numbers of compounds.21
Solution and solid phase synthesis has been used to
generate glycomimetics of cell surface carbohydrates, the
most popular target being sialyl Lewis x.6,22 These
strategies have focused on using non-carbohydrate scaf-
folds in conjunction with commercially available hexoses
to present varied functionality not usually available from
sugars. The compounds have been pursued to limit the
complexity of the oligosaccharide, increase the favorable
protein-ligand interaction, and increase bioavailability.
While not all are combinatorial approaches, many of
these examples have core structures and flexible synthe-
A variety of approaches to carbohydrate diversity in
drug discovery has been reported in recent years, mostly
incorporating commercially available sugars as known
essential recognition elements. The de novo synthesis
of carbohydrates is another option being explored for
preparing diverse carbohydrate structures which may
show preferential binding over available hexoses. To put
our study in perspective, the following three paragraphs
serve as a brief review of the advances in the carbohy-
drate field which have the potential to access the im-
mense diversity available to these biopolymers.
Using the benefits of solid phase synthesis, researchers
have been successful in performing glycosylations with
various sugar donors such as glycosyl halides,13 trichlo-
roacetimidates,14 glycosyl sulfoxides,15 and glycosyl sul-
fides16 or through enzymatic coupling with polymer
bound substrates.17 Other methods rely on the inclusion
of preformed glycosylated amino acids into automated
peptide synthesis18 and the formation of N-linked glyco-
peptides toward the end of the peptide synthesis using
the â-glycosyl amines and activated aspartic acids.19
Danishefsky has formed O-glycosides on solid support
using the glycal technology,20 a method which may prove
(18) (a) Christiansen-Brams, I.; Meldal, M.; Bock, K. J . Chem. Soc.,
Perkin Trans. 1 1993, 1461. (b) J ensen, K. J .; Meldal, M.; Bock, K. J .
Chem. Soc., Perkin Trans. 1 1993, 2119. (c) Meldal, M.; Bock, K.
Glycoconjugate J . 1994, 11, 59. (d) Seitz, O.; Kunz, H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 803. (d) Rio-Anneheim, S.; Paulsen, H.; Meldal,
M.; Bock, K. J . Chem. Soc., Perkin Trans. 1 1995, 1071. (e) Reimer, K.
B.; Meldal, M.; Shoichi, K.; Fukase, K.; Bock, K J . Chem. Soc., Perkin
Trans. 1 1993, 925. (f) Broddefalk, J .; Bergquist, K. E.; Kihlberg, J .
Tetrahedron Lett. 1996, 37, 3011.
(19) (a) Cohen-Anisfeld, S. T.; Lansbury, P. T., J r. J . Am. Chem.
Soc. 1993, 115, 10531. (b) Vetter, D.; Gallop, M. A. Bioconjugate Chem.
1995, 6, 316. (c) Vetter, D. et al. Angew. Chem., Int. Ed. Engl. 1995,
34, 60. (d) Roberge, J . Y.; Beebe, X.; Danishefsky, S. J . Science 1995,
269, 202.
(20) (a) Randolph, J . T.; McClure, K. F.; Danishefsky, S. J . J . Am.
Chem. Soc. 1995, 117, 5712. (b) Randolph, J . T.; Danishefsky, S. J .
Angew. Chem., Int. Ed. Engl. 1994, 33, 1470. (c) Danishefsky, S. J .; et
al. Science 1993, 260, 1307.
(21) The topics in this paragraph have been reviewed in more detail.
Sofia, M. J . Drug Discovery Today 1996, 1, 27.
(22) (a) Armstrong, R. W.; Sutherlin, D. P.; Wolinski, L. Presented
at the 31st Annual Western Regional Meeting of the American
Chemical Society, San Diego, CA, October 18-21, 1995. (b) Rao, N. N.
Presented at the 31st Annual Western Regional Meeting of the
American Chemical Society, San Diego, CA, October 18-21, 1995. (c)
Uchiyama, T.; Vassilev, V.; Kajimoto, T.; Wong, W.; Lin, C.-C.; Huang,
H.; Wong, C.-H. J . Am. Chem. Soc. 1995, 117, 5396. (d) Huryn, D.
Presented at the 31st Annual Western Regional Meeting of the
American Chemical Society, San Diego, CA, October 18-21, 1995. (e)
For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f)
Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R.
V.; Beck, P. J .; Voytus, J . A.; Revelle, B. M.; Scott, D. J . Med. Chem.
1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree,
W. J .; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl.
1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang,
R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt,
G.; Wong, C.-H. J . Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.;
Auer, M.; J aksche, H.; Wong, C.-H. J . Am. Chem. Soc. 1996, 118,
10150.
(11) Thompson, L. A.; Ellman, J . A. Chem. Rev. 1996, 96, 555.
(12) Another obstacle associated with cell surface carbohydrates is
their low affinities for the protein receptors that bind them. This has
been addressed by presenting multivalent ligands through the use of
a variety of structural templates. For an overview of the progress in
this area, see: Kiessling, L. L.; Pohl, N. L. Chem. Biol. 1996, 3, 71.
(13) (a) Frechet, J . M.; Schuerch, C. J . Am. Chem. Soc. 1972, 95,
604. (b) Frechet, J . M.; Schuerch, C. Carbohydr. Res. 1972, 22, 399.
(c) Guthrie, R. D.; J enkins, A. D.; Roberts, G. A. F. J . Chem. Soc.,
Perkin Trans. 1 1973, 2414.
(14) (a) Douglas, S. P.; Whitfield, D. M.; Krepinski, J . J . J . Am.
Chem. Soc. 1995, 117, 2116. (b) Krepinski, J . J .; Douglas, S. P.;
Whitfield, D. M. Methods Enzymol. 1994, 242, 280. (c) Adinolfi, M.;
Barone, G.; De Napoli, L.; Iadonisi, A.; Piccialli, G. Tetrahedron Lett.
1996, 37, 5007.
(15) (a) Yan, L.; Taylor, C. M.; Goodnow, R., J r.; Kahne, D. J . Am.
Chem. Soc. 1994, 116, 6953. (b) Wang, Y.; Zhang, H.; Voelter, W. Chem.
Lett. 1995, 273. (c) Liang, R.; Yan, L.; Loebach, J .; Ge, M.; Uozumi,
Y.; Sekanina, K.; Horan, N.; Gildersleeve, J .; Thompson, C.; Smith,
A.; Biswas, K; Still, W. C.; Kahne, D. Science 1996, 274, 1520.
(16) Nicolaou, K. C.; Winssinger, N.; Pastor, J .; DeRoose, F. J . Am.
Chem. Soc. 1997, 119, 449.
(17) (a) Wong, C.-H.; Schuster, M.; Wang, P.; Sears, P. J . Am. Chem.
Soc. 1993, 115, 5893. (b) Schuster, M.; Wang, P.; Paulson, J . C.; Wong,
C.-H. J . Am. Chem. Soc. 1994, 116, 1135. (c) Meldal, M.; Auzanneau,
F.-I.; Hindsgaul, O.; Palcic, M. M. J . Chem. Soc., Chem. Commun. 1994,
1849.

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5269
Ch a r t 1
sis well-suited for combinatorial library generation.
Another conceptual approach, shown by Hindsgaul, ad-
dresses the possibility of a random glycosylation on an
unprotected glycoside, resulting in a statistical mix of
oligosaccharides in ratios proportional to the reactivity
of each available hydroxyl.23
Preparing diverse carbohydrates de novo from achiral
precursors via solution or enzymatic synthesis is an
attractive alternative to the above approaches.24 These
methods can allow for radically different hexose struc-
tures which may be important for protein-carbohydrate
binding. As examples, the unnatural O-glycosides pre-
pared by Lemieux25 and Hindsgaul26 and C-glycosides
prepared by Kishi27 show that slight modifications in
structure, such as heteroatom deletion or substitution,
can have large effects on binding affinities, providing
valuble information about the active site of receptors and
glycosyltranferases. Glucosidase inhibition by azasugars
also demonstrates the necessity of introducing function-
ality beyond the native structure of a sugar to achieve
enhanced binding affinities.28 Most of the research in
the de novo area has focused on monosaccharides, ben-
efitting greatly from the increased knowledge and suc-
cesses of stereoselective synthesis as well as increased
understanding of enzyme systems. Wong has contributed
to this area by preparing many non-natural monosac-
charides with diverse functionality through an elegant
combination of chemoenzymatic synthesis.29 These ap-
proaches have yet to be applied to the generation of large
numbers of compounds in a combinatorial fashion.
We have been interested in the synthesis of C-di- and
C-trisaccharides in which a particular monomer of inter-
est could be substituted with a diverse set of carbohy-
drates. We feel that the most efficient way to prepare
these sugars with all the possible diastereomeric rela-
tionships of hydroxyl groups as well as other non-natural
functional groups would be through de novo design. This
type of approach has resulted in the synthesis of four
disaccharides, Glucose-R(1-6)-D and L)-galactose and
-idose, in an early report based on the general structure
5 (Figure 1). This common motif (x-6-linked disaccha-
ride) exemplified in NeuNAc-R(2-6)Gal (4) was generated
from the acyclic R,â-δ,γ unsaturated ester 6 via a dihy-
droxylation and reduction procedure. Treatment of the
remaining olefin stereoisomers of 6 with the same reac-
tion conditions would supply the remaining diastereo-
mers.
This paper describes the generation of 11 C-trisaccha-
rides 7-17 (Chart 1) having the formula Fuc-C-(1-2)-
hexose-C-(1-x)-GlcNAc (2), that of the Lewis type I blood
group determinant 1, six of which were presented in a
recent communication,8 and an additional C-saccharide
(18) containing an oxetane as a replacement for the
central sugar. It was necessary that the syntheses of the
compounds have as few steps as possible, be flexible in
allowing different reaction conditions, and be predictable
with respect to the structures’ final stereochemistries.
Interest in the Lewis type I blood group determinant
1 as a recognition point for the cellular adhesion of
Helicobactor pylori to epithelial cells in the gut of some
individuals focused our synthesis of C-trisaccharides on
this structure type. Our synthetic strategy is based on
the C-trisaccharide 2, a mimic of blood group determinant
1. A vast number of candidates that would effectively
model hydroxyl deletions, substitutions, and/or stereo-
chemical inversions was considered for synthesis. Our
goal was to find a lead series of compounds with biological
activity rather than to prepare specific trisaccharides. We
are also interested in the possibility of finding active
library components which have truly novel characteris-
tics, such as a mixed D-L-D trisaccharide. Due to an
individual trisaccharide’s limited probability of success
in a screen, the extremely difficult synthesis required to
make these complex compounds hardly justifies the
effort. As a solution to this dilemma, a strategy was
developed which could rapidly access C-trisaccharides in
a series such as Fuc-hexose-NAcGlc through a divergent
(23) Kanie, O.; Barresi, F.; Ding, Y.; Labbe, J .; Otter, A.; Forsberg,
L. S.; Ernst, B.; Hindsgaul, O. Angew. Chem., Int. Ed. Engl. 1995, 34,
2720.
(24) (a) Tschamber, T.; Backenstrass, F.; Nueburger, M.; Zehnder,
M.; Streith, J . Tetrahedron 1994, 50, 1135. (b) Kobayashi, S.; Kawasuji,
T. Synth. Lett. 1993, 911. (c) Ko, S. Y.; Lee, W. M.; Masamune, S.;
Reed, III, L. A.; Sharpless, K. B.; Walker, F. J . Tetrahedron 1990, 46,
245. (d) Mukaiyama, T.; Suzuki, K.; Yamada, T.; Tabusa, F. Tetrahe-
dron 1990, 46, 265. (e) McGarvey, G. J .; Kimura, M.; Oh, T. J .
Carbohydr. Chem. 1984, 3, 125. (f) Hudlicky, T.; Entwistle, D. A.;
Pitzer, K. K.; Thorpe, A. J . Chem. Rev. 1996, 96, 1195. (g) Goebel, M.;
Ugi, I. Tetrahedron Lett. 1995, 36, 6043. (h) Roush, W. R.; Gustin, D.
Tetrahedron Lett. 1994, 35, 4931. (h) Hudlicky, T.; Abboud, K. A.;
Entwistle, D. A.; Fan, R.; Maurya, R.; Thorpe, A. J .; Bolonick, J .; Myers,
B. Synthesis 1996, 897.
(25) (a) Lemieux, R. U.; Du, M.-H.; Spohr, U. J . Am. Chem. Soc.
1994, 116, 9803. (b) Lemieux, R. U.; Du, M.-H.; Spohr, U.; Acharya,
S.; Surolia, A. Can. J . Chem. 1994, 72, 158.
(26) (a) Lowary, T. L.; Hindsgaul, O. Carbohydr. Res. 1993, 249,
163. (b) Khan, S. H.; Crawley, S. C.; Kanie, O.; Hindsgaul, O. J . Biol.
Chem. 1993, 268, 2468.
(27) (a) Haneda, T.; Goekjian, P.; Kim, S. H.; Kishi, Y. J . Org. Chem.
1992, 57, 490. (b) Wei, A.; Haudrechy, A.; Audin, C.; J un, H.-S.;
Haudrechy-Bretel, N.; Kishi, Y. J . Org. Chem. 1995, 60, 2160. (c) Wei,
A.; Boy, K. M.; Kishi, Y. J . Am. Chem. Soc. 1995, 117, 9432.
(28) (a) Wang, Y.-F.; Takaoka, Y.; Wong, C.-H. Angew. Chem., Int.
Ed. Engl. 1994, 33, 1242. (b) Sinnott, M. L. Chem. Rev. 1990, 90, 1171.
(c) Winchester, B.; Fleet, G. W. Glycobiology 1992, 2, 199. (d) Look, G.
C.; Fotsch, C. H.; Wong, C. H. Acc. Chem. Res. 1993, 26, 182.
(29) (a) Henderson, I.; Sharpless, K. B.; Wong, C.-H. J . Am. Chem.
Soc. 1994, 116, 558. (b) Wong, C.-H.; Halcomb, R. L.; Ichikawa, Y.;
Kajimoto, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 412. (c) Harrie, J .
M.; Qiao, L.; Fitz, W.; Wong, C.-H. J . Chem. Rev. 1996, 96, 443.

5270 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
describes the synthesis of eight bis-THF acetogenin
diastereomers through an approach which could be
coupled with a RSD strategy to potentially reduce the
number of synthetic steps.32
For example, reactions performed on A to generate B
and then BC compounds could give results ranging from
one pool of all four compounds to four separate pools with
pure compounds in each pool. In the event that a pool
containing B1C1 and B1C2 compounds was found to elicit
interesting activity worthy of a structural determination,
an archived amount of B1 could be submitted to a
predictable stereoselective route that would significantly
favor the formation of C1 over C2. If the stereochemically
biased pool was found by a screen to be more active than
the original pool, the B1C1 compound would be identified
as the active component.
F igu r e 2. Schematic of the recursive strereochemical decon-
volution process.
route. We planned to test compounds as diastereomeric
mixtures that could later be deconvoluted to their ster-
eochemical identity. The groundwork for this approach
is presented herein, demonstrated with the use of a
recursive stereochemical deconvolution (RSD)30 that may
be applied to the synthesis of many of these trisaccha-
rides and possibly other natural products and their
derivatives if a similar strategy is employed.31
To apply this approach to C-trisaccharides 2, two fixed
pendant sugars were positioned at each terminus of the
trisaccharide and the central core hexose was created de
novo. Strategically, the pendant sugars identity and
connectivity could be easily changed, making this a
convergent approach, general for any trisaccharide of
interest with C-1 and C-2 linkages. In addition, permu-
tational alterations of the central hexose should have the
most effect on the overall three-dimensional conformation
of the trisaccharide. C-Glycosides were also an essential
part of our overall scheme due to their resistance to both
chemical and enzymatic hydrolysis.33 In most cases this
carbon for oxygen substitution has little effect on the
compounds’ solution conformation or binding affinity to
natural ligands compared to their O-glycosidic counter-
parts and can be used for therapeutic applications.27c,34
Retrosynthetic analysis of 2 affords the complex “C-
disaccharide” 3, possessing both pendant sugars, which
can be modified by the addition of a variety of nucleo-
philes and then converted synthetically to 2 via an
intramolecular cyclization. Synthesis of compounds re-
sembling the protected â-hydroxy aldehyde 3 required a
coupling of two advanced carbohydrate intermediates,
both derived from natural sugar precursors. This strat-
egy has thus far yielded 12 trisaccharides through a
rapid, convergent approach that can be applied to a
variety of cell surface sugars. It is also important to note
that both the central D and L sugars are synthesized with
no extra synthetic effort, providing a permutation that
would otherwise be financially prohibitive if natural
sugar precursors were used as starting materials. First,
the synthesis of six 2,4-dideoxy C-trisaccharides will be
presented, and second, a variety of other C-trisaccarides
will be described to highlight the flexibility of the route.
This synthetic approach to C-trisaccharides coupled
with a novel deconvolution strategy represents a practical
method to rapidly prepare and sort unnatural C-trisac-
charides via biological evaluation of diastereomeric mix-
tures. This strategy differs from recursive deconvolution
in that the researcher is deconvoluting stereochemistry,
performed through stereoselective synthesis, rather than
deconvoluting structure by identifying library inputs. The
absolute structure of a compound of interest can be
determined via a recursive treatment of an active pool
of diastereomeric mixtures through further elaboration
of archived intermediates and subsequent retesting.
Ideally, each transformation can be performed in a
nonselective as well as a stereoselective fashion (Figure
2). In the first pass, a rapid protocol that would elicit
limited selectivity would be used, creating a mixture of
diastereomers. Prior to each stereogenic step, material
would be archived for later use. If a pool of end product
compounds is identified from a biological assay as active,
then an elucidation of the absolute stereochemistry could
be attempted using conventional methods (i.e., X-ray,
NMR). Alternatively, previously archived material would
be used to perform the second set of reliable, previously
investigated stereoselective chemical steps that has an
influence on the end product ratios. Comparison of the
activity in the original compound pool with that of the
newly synthesized, stereochemically biased compound
pools would identify the absolute structure of the com-
pound of interest. This process of rapid synthesis of
compounds in diastereomer pools goes against the es-
tablished paradigm of syntheses employing a high degree
of stereocontrol. However, given the stereochemical
complexity of these and other products, along with the
particular strengths of combinatorial chemistry, this type
of approach to novel therapeutics is attractive. For
instance, a recent publication by Sinha and Keinan
Resu lts a n d Discu ssion
A convergent approach to the disaccharide was sought
that would function as the starting point for further
(32) Sinha, S. C.; Sinha, A.; Yazbak, A.; Keinan, E. J . Org. Chem.
1996, 61, 7640.
(33) (a) Postema, M. H. D. Tetrahedron 1992, 48, 8545-8599. (b)
Wei, A.; Haudrechy, A.; Audin, C.; J un, H.-S.; Haudrechy-Bretel, N.;
Kishi, Y. J . Org. Chem. 1995, 60, 2160.
(30) This process is a modification of J anda’s recursive deconvolution
of combinatorial libraries. Erb, E.; J anda, K. D.; Brenner, S. Proc. Natl.
Acad. Sci. U.S.A. 1994, 91, 11422.
(31) For other strategies for preparing and deconvoluting compounds
from pools, see: (a) Sepetov, N. F.; Krchnak, V.; Stankova, M., Wade,
S.; Lam, K. S.; Leble, M. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5426.
(b) Smith, P. W.; Lai, J . Y. Q.; Whittington, A. R.; Cox, B.; Houston, J .
G. BioMed. Chem. Lett. 1994, 4, 2821. (c) Pirrung, M. C.; Chen, J . J .
Am. Chem. Soc. 1995, 117, 1240. (d) Carell, T.; Wintner, E. A.; Rebek,
J . Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
(34) (a) Nagy, J . O.; Wang, P.; Gilbert, J . H.; Schaefer, M. E.; Hill,
T. G.; Callstrom, M. R.; Bednarski, M. D. J . Med. Chem. 1992, 35,
4501. (b) Bertozzi, C. R.; Cook, D. G.; Kobertz, W. R.; Gonzalez-Scarano,
F.; Bednarski, M. D. J . Am. Chem. Soc. 1992, 114, 10639. (c) Bertozzi,
C. R.; Bednarski, M. D. J . Am. Chem. Soc. 1992, 114, 5543. (d) Mortell,
K. H.; Weatherman, R. V.; Kiessling, L. L. J . Am. Chem. Soc. 1996,
118, 2297. For exceptions, see: (e) Espinosa, J .-F.; Canada, F. J .;
Asensio, J . L.; Dietrich, H.; Martin-Lomas, M.; Schmidt, R. R.; J imenez-
Barbero, J . Angew. Chem., Int. Ed. Engl. 1996, 35, 303. (f) O’Leary,
D. J .; Kishi, Y. J . Org. Chem. 1994, 59, 6629.

Stereochemically and Structurally Diverse C-Trisaccharides
Sch em e 1a
J . Org. Chem., Vol. 62, No. 16, 1997 5271
a
Reagents and conditions: (a) BnOH, AcCl; (b) 2,2-dimethoxypropane, PTSA; (c) KH, CS2, MeI, THF; (d) allyltributyltin, AIBN, THF,
65 °C; (e) O3, PBu3, CH2Cl2, -78 °C; (f) 9-BBN, THF, 0 °C; (g) Dess-Martin periodinane, CH2Cl2; (h) allylmagnesium bromide, THF, -78
°C; (i) TBAF, THF, or Et2O; (j) MCPBA, CH2Cl2; (k) catalytic CSA, CH2Cl2; (l) H2, Pd(OH)2/C, MeOH.
manipulations, eventually forming the center hexose
(Scheme 1). After attempting three alternative methods
for the synthesis of structure 3, we decided to rely on
the CrCl2/NiCl2 coupling35 due to its compatibility with
a large number of protecting groups, a strategy effective
for Kishi in the synthesis of C-sucrose.36 This coupling
required the vinyl bromide C-fucose (Fuc) 1937 and the
C-3-homologated acetaldehyde of N-acetylglucose (GlcNAc)
20. Fucose derivative 19 was analogous to a C-glucose
vinyl bromide used by Kishi in the previously mentioned
report and was prepared in the same manner. GlcNAc
was selectivly protected by first forming the benzyl
glycoside followed by the formation of a six-membered
acetonide between the C-6 and C-4 hydroxyls. This
protection scheme made available the C-3 hydroxyl which
could be converted smoothly to the methyl xanthate 22.
The AIBN-initiated radical allylation between the xan-
thate and allyltributyltin effected the essential oxygen
to carbon replacement, resulting in the equatorial product
exclusively. Attempts to replace the acetonide with
benzyl groups in a deprotection/protection strategy to
provide protecting groups identical to those used on the
fucose moiety failed due to the inaccessibility of the C-4
hydroxyl under NaH/BnBr benzylation conditions. Ozo-
nolysis of the olefin followed by reduction of the ozonide
with tributylphosphine afforded the desired aldehyde 20.
With the two modified monosaccharides in hand, we
then began to investigate the organometallic coupling
and subsequent conversions that would lead to aldehydes
like 3. The vinyl bromide 19 was sufficiently active in
the chromium coupling, and although the reaction was
slow, the excess vinyl bromide starting material was
(35) (a) Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H.
Tetrahedron Lett. 1983, 24, 5281. (b) Cintas P. Synthesis 1992, 248.
(c) Hashmi, A. S. K. J . Prakt. Chem. 1996, 338, 491.
(36) (a) Dyer, U. C.; Kishi, Y. J . Org. Chem. 1988, 53, 3383-3384.
(b) Kishi Y. Pure Appl. Chem. 1992, 64, 343-350.
(37) Hosomi, A.; Sakata, Y.; Sakurai, H. Tetrahedron Lett. 1984, 25,
2383.

5272 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
reisolated intact with little reduction of the carbon-
halogen bond. This allowed an increase of the nickel
chloride concentration to 0.5%, thus facilitating an ef-
ficient coupling in a diastereomeric ratio of 1:2 as
determined by protection with TBSOTf, followed by
separation of the corresponding silyl ether derivatives 23
and 24. The relative and absolute stereochemistry of 23
was assigned via X-ray crystallography,58 therefore as-
signing 24 by corollary (vide infra). We next turned our
attention to the stereoselective hydroboration of the
allylic TBS ethers. Our substrates were incompatible
with the catecholborane or catecholborane/Wilkinson’s
catalyst method.38 This prompted the use of 9-BBN to
effect the stereoselective hydroboration which formed the
chiral primary alcohols,39 a strategy used by Evans in
his synthesis of lonomycin A.40 Although hydroborations
on the unprotected allylic alcohols with BH3 were suc-
cessful, attempts with the TBS-protected allylic alcohol
were discouraging. Oxidation of the primary alcohols
following Swern conditions resulted in â-elimination
whereas the Dess-Martin periodinane (DMP)41 oxidized
the alcohols smoothly in near quantitative yield, giving
aldehydes 25 and 34.
At this point we examined the nucleophilic additions
necessary to complete the carbon skeleton and form the
hexose core structure. Aldehyde 25 was homologated by
the addition of allylmagnesium bromide to yield sepa-
rable homoallylic alcohols 26 and 27 in a 2:1 ratio,
respectively. The major diastereomer 26 resulted from
a Felkin-Ahn addition of the nucleophile to the aldehyde.
Next, routes that favor either diastereomer were inves-
tigated. This was essential to our future goal of deter-
mining an unknown structure from active compound
pools via a recursive stereochemical deconvolution. Chiral
allylboration42 using the (+)-Ipc2BOMe ligand gave the
homoallylic alcohols in a 6:1 ratio, as predicted, in a 48%
yield.43 The (-)-Ipc2BOMe ligand was unable to override
the Felkin-Ahn induction. As a viable alternative, the
other diastereomer could be favored by oxidizing the
alcohol to the â,δ-unsaturated ketone with DMP and
subsequently reducing the crude ketone with LiBH4,
giving a 1:3 ratio of diastereomers in 95% yield.44
Compounds 26 and 27 were then separately desilylated
with TBAF to give diols 28 and 29, respectively. The
olefin in diol 28 was oxidized with MCPBA to yield a 1:1
mixture of epoxides which was subsequently treated with
CSA, resulting in six-membered ring cyclization and
removal of the isopropylidene protecting group from the
N-acetylglucosamine. Oxidation with methyl(trifluoro-
methyl)dioxirane also provided the epoxides in good
yields.45 Hydrogenation using H2 with Pearlman’s cata-
lyst removed all but the anomeric benzyl group, limiting
the diastereomers formed to the two C-trisaccharides 12
and 1346 containing the center sugar 2,4-dideoxy-L-
galactose for 13 and 2,4-dideoxy-D-altrose for 12. These
sugars may alternatively be referred to as 2,4-dideoxy-
L-glucose for 13 and 2,4-dideoxy-D-idose for 12 due to the
lack of the hydroxyl on C-4 found in the natural hexoses.
Fortunately, due to its slower rate of hydrogenation, the
anomeric benzyl group was retained, simplyfing the
proton NMR spectra of the end products.
Trisaccharides 14 and 15 were generated from diol 29
in a similar manner combining the epoxidation, cycliza-
tion, and deprotection in one step by adding CSA directly
to the flask containing MCPBA after 16 h had elapsed.
Selective deprotection of the benzyl groups on the fucose
gave two trisaccharides 14 and 15 that could be separated
by normal flash silica gel chromatography.47 These two
compounds have the center sugars 2,4-dideoxy-L-allose
in 15 and 2,4-dideoxy-D-mannose in 14.48
Aldehyde 34 was allylated, and the crude reaction
mixture was treated with TBAF to remove the TBS ether,
providing compound 35 as expected from Felkin-Ahn
addition of the nucleophile, exclusively. The allylated
precursor to 35 could be treated with the oxidation
(DMP)/reduction (LiBH4) procedure to obtain a 1:1 mix-
ture of alcohol diastereomers when benzene was used as
the solvent. Interestingly, the LiBH4 reduction of the
ketone in THF still afforded the Felkin-Ahn product as
the major diastereomer, contrary to what was observed
when these same procedures were performed on com-
pounds 26 and 27. Other reduction conditions using
L-Selectride, LAH, and DIBAL-H were unsuccessful. It
was not until the reduction was performed in a nonpolar
solvent that the 1:1 ratio of diastereomers was obtained.
Satisfied with this result, chiral allylborations were not
attempted. Compound 35 was treated with the one-pot
epoxidation/cyclization procedure to give two separable
trisaccharides. Both compounds were selectively hydro-
genated and separated to give pure C-trisaccharides 8
with 2,4-dideoxy-D-galactose as the central sugar and 7
with 2,4-dideoxy-L-altrose as the central sugar.49,50
(45) Yang, D.; Wong, M.-K.; Yip, Y.-C. J . Org. Chem. 1995, 60, 3887.
(46) Compounds 8 and 9 could be separated via chromatography
following an acetylation step.
(47) Two fractions were obtained, one with 10% contamination by
the other diastereomer and the other with a 15% contamination of the
previous diastereomer.
(48) Or 2,4-dideoxy-L-gulose for 15 and 2,4-dideoxy-D-talose for 14.
(49) Or 2,4-dideoxy-D-glucose for 8 and 2,4-dideoxy-L-idose for 7.
(50) The tetrabenzylated precursors to 7 and 8 were individually
analyzed via 2D COSY, 2D ROESY, and 2D HMQC to establish proton
connectivity and then selectively decoupled to determine J values of
individual resonances. This analysis resulted in the stereochemical
assignment of these compounds. It was also at this point that the
stereochemical outcomes of hydroboration and Felkin-Ahn addition
for this series were confirmed. The stereochemistry of C-1 carbon (of
the center sugar) in the precursor to 8 was known from X-ray
crystallography and its proton was coupled to the C-2 proton with a
large J value of 9.8 Hz, indicative of a trans-trans diaxial relationship.
The C-3 proton was likewise coupled to C-2 with a 10.4 Hz coupling in
addition to couplings with the C-4 axial proton (10.4 Hz) and to the
C-4 equatorial proton (4.2 Hz). The C-4 equatorial proton, in addition
to a geminal coupling to the C-4 axial proton (12.0 Hz), is weakly
coupled to C-5, a pattern similar to the C-4 proton of galactose found
in a previously synthesized C-1, C-2 branched C-trisaccharide (see ref
26a). The benzylated precursor to 7 was analyzed in a similar manner
but was thought not to exist as a chair due to the combination of the
unfavorable A 1,2 strain in the C-1 and C-2 branch points of the center
sugar and the 1,3-diaxial interactions caused by C-6. This resulted in
a more complicated spectrum with many small couplings between the
ring protons, causing broader lines.
(38) (a) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J . Am. Chem. Soc.
1988, 110, 6917. (b) Evans, D. A.; Fu, G. C. J . Org. Chem. 1990, 55,
2280. (c) Burgess, K.; Donk, W. A. van der; Westcott, S. A.; Marder, T.
B.; Baker, R. T.; Calabrese, J . C. J . Am. Chem. Soc. 1992, 114, 9350.
(d) Burgess, K.; Ohlmeyer, M. J . Chem. Rev. 1991, 91, 1179.
(39) Since these alcohols were isolated as single diastereomers,
presumably in 95% or greater de, we were inclined to assign their
stereochemistry on the basis of examples at this preliminary stage.
The assignment of these centers was later confirmed through proton
NMR experiments performed on cyclic intermediates.
(40) Evans, D. A.; Ratz, A. M.; Huff, B. E.; Sheppard, G. S. J . Am.
Chem. Soc. 1995, 117, 3448-3467.
(41) (a) Dess, D. B.; Martin, J . C. J Org. Chem. 1983, 48, 4156. (b)
Ireland, R. E.; Liu, L. J Org. Chem. 1993, 58, 2899. (c) For preparation,
follow Meyer, S. D.; Schreiber, S. L. J Org. Chem. 1994, 59, 7549.
(42) (a) Brown, H. C.; J adhau, P. K. J . Am. Chem. Soc. 1983, 105,
2092. (b) Brown, H. C.; J adhau, P. K.; Bhat, K. S. J . Am. Chem. Soc.
1988, 110, 1535. (c) Brown, H. C.; Ramachandran, P. V. J . Organomet.
Chem. 1995, 500, 1.
(43) This assignment was further confirmed by NMR analysis of the
tetrabenzylated 15.
(44) Scarlato, G. R.; DeMattei, J . A.; Chong, L. S.; Ogawa, A. K.;
Lin, M. R.; Armsrtong, R. W. J . Org. Chem. 1996, 61, 6139.

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5273
Sch em e 2a
Sch em e 3a
a
Reagents and conditions: (a) 2,6-lutidene, TBSOTf; (b) OsO4,
DHQD2‚pyr, t-BuOH/H2O, 0 °C, 5:1 diastereomers; (c) Et3N, MsCl,
CH2Cl2; (d) NaH, Et2O; (e) TBAF, THF, or Et2O; (f) catalytic CSA,
CH2Cl2; (g) H2, Pd(OH)2/C, MeOH.
Deconvolution of the C-5 stereocenter was addressed
by generating a stereochemically pure epoxide starting
from the anti Felkin-Ahn product, minor diastereomer
27 (Scheme 2). After TBS protection, the disilane was
submitted to Sharpless asymmetric dihydroxylation con-
ditions,51 generating the desired chiral diol 30. Dihy-
droxylation with the DHQD ligand proceeded in good
yield, providing a 5:1 ratio of separable diastereomers.
The alternative DHQ ligand gave the diols in an opposite
1:2 ratio. Careful addition of 1 equiv of MsCl with excess
TEA gave the primary mesylate. Base-mediated ring
closure of the mesylate formed the epoxide 31.52 Depro-
tection of both TBS protecting groups gave stereochemi-
cally pure dihydroxy epoxide 32 that converged on the
nonstereoselective route, using MCPBA to epoxidize
compound 29. As expected, when this diol was treated
with the previous conditions of acid-catalyzed cyclization
and then hydrogenation, C-trisaccharide 14 was gener-
ated as a single compound and compared spectroscopi-
cally to the two trisaccharides obtained from the previous
nonstereoselective epoxidation. Only then were we able
to assign the absolute stereochemistry of both separated
compounds 14 and 15. As a side note, we initially
attempted this route using a benzyl-protected C-3 hy-
droxyl rather than the TBS used in 26. This protection
was necessary to prevent five-membered ring cyclization
by this hydroxyl with the primary mesylate under the
conditions of epoxide formation. All chemical steps
identical to those used to prepare 32 proceeded smoothly
upto the CSA cyclization step, resulting only in isolation
of starting material. The cyclization of this compound
was presumably hindered by the sterics of the benzyl
ether protecting group, requiring the switch to the
orthogonal and removable TBS protecting group.
a
Reagents and conditions: (a) O3, NaBH4, MeOH; (b) Et3N,
MsCl, CH2Cl2; (c) TBAF; (d) PTSA, CH2Cl2, MeOH; (e) Pd(OH)2/
C, H2, MeOH; (f) allylmagnesium bromide.
could be determined via the comparative testing of
diastereomerically enriched pools of compounds, archived
at each prochiral stage (i.e., 24, 25, and 29). The
synthesis is both convergent with respect to the pendant
sugars and divergent so that modifications of steps in
the later portions of the route can be used to generate a
variety of alternative structures.
We now wish to demonstrate the flexible nature of this
strategy in the preparation of six additional hexoses.
C-Glycosides 9-11 and 16-18 were targeted to comple-
ment the previously described compounds, representing
further modifications of the central hexose. These de-
rivatives were synthesized by the utilization of two
different cyclization methods to make des C-6 and
6-deoxy sugars; the incorporation of an alternative nu-
cleophile to include a hydroxyl at C-4 and cyclization
prior to carbon homologation to prepare ring-contracted
structures.
To prepare the des C-6 compounds 11 and 16, olefin
27 was ozonized and reduced to the 1,3-diol (Scheme 3).
The primary hydroxyl group was then mesylated by 1
equiv of MsCl to yield 36. Deprotection and cyclization
occurred in one pot with the addition of TBAF in THF.
All that remained to be performed was the acid removal
of the acetonide and benzyl hydrogenation of 37 to
generate 16. This central sugar represents the six-
membered-ring pentose 2,4-dideoxy-L-ribose. Although
the C-4 hydroxyl, the defining element of D or L absolute
stereochemistry in five-membered sugars, has been re-
moved, the stereochemical distiction must be made in
order to establish the relative stereochemistry at C-2 and
C-3. The same steps were followed to prepare compound
11, with 2,4-dideoxy-D-xylose as the central sugar. It is
important to note that compounds 37 and 38 contain a
free hydroxyl which may be further functionalized via
alkylation or glycosylation in order to prepare higher-
order compounds.
We believe that this research can now be applied to
the generation of large numbers of sugars with a central
carbohydrate that is equatorially branched at C-1 and
C-2 and deoxygenated at C-4 simply by incorporating
pendant sugars other than Fuc and GlcNAc. A structure
generated in this manner that elicits a biological response
(51) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483.
(52) Wang, Y.; Babirad, S. A.; Kishi, Y. J . Org. Chem. 1992, 57, 468-
481.
We then focused on the C-6 deoxy sugars 9 and 10 via
an alternative cyclization technique. These compounds

5274 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
Sch em e 5a
Sch em e 4a
a
a
Reagents and conditions: (a) Hg(O2CCF3)2, NaCl, THF; (b) 1
Reagents and conditions: (a) Brown allylboration with MOM
equiv of NaBH4, DMF; (c) excess NaBH4, DMF; (d) PTSA, CH2Cl2,
MeOH; (e) Pd(OH)2/C, H2, MeOH.
allyl ether, (-)-Ipc2BOMe, t-BuOK, n-BuLi, THF; (b) PTSA,
CH2Cl2, MeOH; (c) Hg(O2CCF3)2, NaCl, THF; (d) excess NaBH4,
DMF; (e) HCl, MeOH; (f) Pd(OH)2/C, H2, MeOH.
would represent an interesting permutation of the C-4
deoxy compounds 7 and 8 when compared with the des
C-6, C-4 deoxy 11. Oxymercuration-demercuration
seemed to be the best route to these compounds and has
been demonstrated in the literature for monosaccha-
rides.53 The diol 35 was intramolecularly oxymercurated
with highly reactive mercury bis(trifluoroacetate) in
excellent yield with no stereoselectivity observed (Scheme
4). Reductive demercurations using NaBH4 on cyclic
substrates of this type are typically performed with phase
transfer catalysts and NaOH to discourage the reverse
deoxymercuration, which would result in isolation of the
ring-opened starting material used prior to mercury
addition.54 This was indeed the case when 39 was
treated with 1 equiv of NaBH4 in DMF, resulting in the
isolation of olefin 35 as the major product However, when
excess borohydride in DMF was used, reduction to the
corresponding C-6 deoxy sugars occurred very smoothly
to afford 41 and 42 after deprotection of the acetonide.
We are presently unaware of reductive demercurations
performed in DMF without NaOH, nor do we know if this
represents a general method for the reduction of mercury-
carbon bonds in similar systems. Compounds 41 and 42
were then fully deprotected to give the C-trisaccharide
10 with a 2,4,6-trideoxy-D-galactose center sugar and
C-trisaccharide 9 with a 2,4,6-trideoxy-L-altrose center
sugar, respectively. The stereochemistry of the newly
formed stereogenic center was tentatively assigned
through proton NMR decoupling experiments of 41 and
42.55
allylborated using MOM-protected allylalcohol and the
(-)-Ipc2BOMe chiral ligand to give 43 in reasonable
yields and high enantioselectivity (Scheme 5). Allylations
using THP-protected allyl alcohol occurred in unsatisfac-
tory yields, prompting the use of the MOM-protected
version. Both the TBS ether and acetonide could be
removed under the mildly acidic conditions previously
demonstrated. We chose to prepare a C-6 deoxy sugar
and therefore added Hg(TFA)2 to effect the oxymercura-
tion. Surprisingly, the crude NMR of the product con-
tained a single compound which was expected to have
an equatorial C-6 in analogy to a literature example53
and through a comparison of proton NMR spectra of other
related examples. Following reductive demercuration
using excess NaBH4 in DMF and subsequent removal of
the MOM protecting group under methanolic HCl condi-
tions, compound 44 was produced. We were unable to
remove the MOM protecting group with TFA or bro-
mocatecholborane, after allylboration.56 In both cases,
the result was rapid cleaveage of the acetonide and TBS
ether with the MOM group remaining. Debenzylation
gave C-trisaccaride 17 with 2,6-dideoxy-L-idose as the
center sugar. The stereochemistry of this ring was
tentatively assigned through decoupling and NOE NMR
experiments.57
Other nucleophiles have been investigated in our labs.
Vinyl Grignard additions have been successful, more so
with aldehyde 25 than 34 which gives more â-elimina-
tion, presumably due to the hard anion character at the
vinyl position. One of these compounds has been con-
verted to a furanose trisaccharide, although in poor yield.
Other chiral enolate reactions can be envisioned that
would provide diverse possibilities such as C-4 alkyl or
amino substituents.
There are many alternative nucleophiles that could be
added to aldehydes 34 and 25. Brown allylborations
using a protected allylic alcohol as the carbon source
would provide sugars with a C-4 hydroxyl. As an
example of the progress in this area, aldehyde 34 was
(53) (a) Bernotas, R. C.; Ganem, B. Tetrahedron Lett. 1985, 26, 1123.
(b) Pougny, J .-R.; Nassr, M. A. M.; Sinay, P. J . Chem. Soc., Chem.
Commun. 1981, 375.
(54) Benhamou, M. C.; Etemad-Moghadam, G.; Speziale, V.; Lattes,
A. Synth. Commun. 1979, 891.
(55) For compound 41 the two methyl resonances were irradiated
to identify the neighboring C-5 protons. The C-5′ proton of the central
hexose was distinguished from the C-5′′ proton of the of the fucose by
selectively spin-saturating these resonances and looking for an effect
in the upfield methylene region. Irradiation of the C-6 methyl protons
of the central hexose collapsed the C-5′ resonance to a doublet of
doublets having identical J values of 4.2 Hz. This pattern is indicative
of an equatorial proton in a six-membered ring chair with two small
couplings to a R methylene.
(56) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; 2nd ed.; Wiley-Interscience: New York, 1991.
(57) The C-4′, C-5′, and C-6′ protons for the central sugar were
unequivocally assigned with 1H decouplings. The C-4′ stereocenter was
assumed to have an axial proton derived from the (Z)-boronenolate in
the Brown allylboration. This was confirmed via a 9.1 Hz coupling to
the C-3′ proton, also axial. Irradiation of the C-5′ proton gave an NOE
with the C-6′ and C-4′ protons however, irradiation of either the C-4′
or C-6′ protons could not indicate an NOE between each other. This
established a C-4′ proton to C-6′ diaxial relationship.
(58) The author has deposited atomic coordinates for structure 23
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5275
Sch em e 6a
360 MHz spectrometers in CDCl3, CD3OD, or d6-acetone.
Proton and carbon spectra were referenced to residual solvent
7.26 and 77.0 ppm for chloroform, 3.3 and 49.0 ppm for
methanol, and 2.3 and 29.8 ppm for acetone, respectively. For
HRMS 4 ppm ) (2 σ. Ozone was produced by O2 and a
Polymetrics T-816 ozone generator.
Com p ou n d 19. A solution of methyl 2,3,4-tribenzylfucoside
(30.6 mg, 68.2 mmol) and 2-bromo-3-(trimethylsilyl)propene
(85.2 mmol; see: Trost, B. M.; Grese, T. A.; Chan, M. T. J .
Am. Chem. Soc. 1991, 113, 7350-7362 (method B) in 50 mL
of CH3CN was treated with TMSOTf (6.80 mL, 34.1 mmol).
After the solution was stirred for 15 h, the reaction was
quenched with 200 mL of a saturated NaHCO3 solution and
diluted with 200 mL of CH2Cl2 (TLC in 4/1 hex/EtOAc). The
aqueous layer was extracted with CH2Cl2 (3 × 200 mL). The
product was purified by chromatography to yield 30.5 g of 19
(83% yield). IR (neat): υmax 2870, 1632, 1497, 1455, 1350,
a
Reagents and conditions: (a) 9-BBN, THF; (b) Et3N, MsCl,
CH2Cl2; (c) TBAF; (d) PTSA, CH2Cl2, MeOH; (e) Pd(OH)2/C, H2,
MeOH.
Finally, we have employed the methods used to create
11 and 16 in the synthesis of a four-membered-ring
hexose isostere. Despite the loss of the central sugar,
alternative ring sizes can be used to examine the vectorial
relationships of the C-1 and C-2 branch points by
representing a distorted dihedral angle as do sugars with
axial substituents at C-6 such as C-trisaccharide 7. The
alcohol resulting from the hydroboration of 24 was
mesylated to yield 45. This compound was then treated
with TBAF, causing the removal of the TBS protecting
group and cyclization in one step (Scheme 6). This
oxetane was further deprotected to give compound 18.
1100, 1071, 735, 696 cm-1 1H NMR (400 MHz, CDCl3): δ 7.39
.
(m, 15H), 5.67 (d, 1H, J ) 1.1 Hz), 5.53 (d, 1H, J ) 1.5 Hz),
4.83 (d, 1H, J ) 12.2 Hz), 4.79 (d, 1H, J ) 12.0 Hz), 4.75 (d,
1H, J ) 12.2 Hz), 4.67 (d, 1H, J ) 11.9 Hz), 4.66 (d, 1H, J )
11.9 Hz), 4.57 (d, 1H, J ) 11.8 Hz), 4.47 (ddd, 1H, J ) 3.7,
3.7, 9.5 Hz), 4.04 (m, 1H), 3.86 (m, 3H), 2.86 (dd, 1H, J ) 9.5,
15.2 Hz), 2.65 (dd, 1H, J ) 3.9, 15.2 Hz), 1.42 (d, 3H, J ) 6.7
Hz). 13C NMR (100.6 MHz, CDCl3): δ 138.6, 138.4, 137.9,
130.8, 128.3, 128.3, 128.2, 127.9, 127.8, 127.7, 127.5, 127.4,
127.4, 118.6, 76.4, 76.2, 75.4, 72.9, 72.8, 72.7, 69.0, 39.7, 14.9.
HRMS (FAB): M+ (Br 80) calcd 535.1484, found 535.1489. [R]D
) -37.6° (c 0.0127, CH2Cl2).
Con clu sion
Ben zyl 4,6-Isop r op ylid en e-N-a cetyl-r-D-glu cosid e. N-
Acetyl-R-D-glucosamine (8.76 g, 39.6 mmol) was stirred over-
night with 100 mL of BnOH and 2.2 mL of AcCl (30.9 mmol)
at 72 °C. After cooling, the BnOH was diluted with excess
Et2O, precipitating out the benzyl glycoside as a brown solid
(see: Flowers, H. M.; Shapiro, D. J . Org. Chem. 1965, 2041-
2043). The solid was filtered and washed with Et2O. This
crude product was combined with 200 mL of DMF and stirred
for 6 h with 18 mL of 2,2-dimethoxypropane (146 mmol) and
145 mg of PTSA (0.76 mmol). Solid NaHCO3 was added. After
filtration and evaporation of the filtrate, chromatography was
performed to isolate 8.8 g of the R-anomer (63%) and 1.8 g of
the â-anomer. IR (neat): υmax 3306, 2994, 2940, 1655, 1549,
In conclusion, this paper presents a unique way to
prepare a diverse set of C-trisaccharides in a rapid
manner. In order to prepare all the possible diastereo-
mers of a particular arrangement of functional groups
using the same chemical steps, a few sacrifices were
made, namely, the isolation of diastereomeric mixtures
in some cases. To account for this, other reaction
conditions have been developed to bias the diastereomeric
mixtures so that a recursive stereochemical deconvolution
procedure can be employed. This RSD strategy repre-
sents a new possibility for preparing and sorting com-
pounds with a complex stereochemical content and may
be useful for the solution phase combinatorial chemistry
of these and other types of structures.
1375, 1127, 1075, 737, 698 cm-1 1H NMR (400 MHz, CDCl3):
.
δ 7.28 (m, 5H), 4.83 (d, 1H, J ) 11.9 Hz), 4.39 (d, 1H, J ) 11.9
Hz), 4.08 (m, 1H), 3.77-3.58 (m, 5H), 1.89 (s, 3H), 1.45 (s, 3H),
1.37 (s, 3H). 13C NMR (90 MHz, CDCl3): δ 171.2, 136.8, 128.3,
127.9, 127.8, 99.5, 97.1, 74.3, 69.5, 63.6, 62.0, 54.0, 28.8, 18.9.
HRMS (FAB): M + H calcd 352.1760, found 352.1764. [R]D
) +82° (c 0.024, CHCl3).
Exp er im en ta l Section
Com p ou n d 22. Benzyl 4,6-Isopropilidene-N-acetyl-R-D-
glucoside (8.8 g, 25.0 mmol) was dissolved in 200 mL of THF
and stirred at room temperature. Deoiled KH (1.21 g, 30.1
mmol) and CS2 (1.96 mL, 32.6 mmol) were added 45 min apart.
After an 45 additional min, MeI (2 mL, 32.6 mmol) was added
Gen er a l P r oced u r es. Reactions were carried out in flame-
dried glassware under an inert atmosphere of nitrogen.
Solvents and reagents were distilled immediately prior to
use: THF and Et2O from sodium/benzophenone ketyl, metha-
nol from magnesium turnings, CH2Cl2 from P2O5, and toluene
from CaH2. Anhydrous DMF, BnOH, and CH3CN were
purchased from Aldrich and used directly. The protected-
sugar starting materials were azeotropically dried three times
with toluene on a rotary evaporator, venting to nitrogen prior
to use. All combined solvents from extractions were dried with
Na2SO4 (except for the hydrogenation reactions), filtered, and
evaporated to dryness. Thin-layer chromatography was per-
formed on silica gel with precoated glass plates (E. Merck
Brinkman, Kieselgel 60 F254, 0.25 mm) and visualized with
UV light, p-anisaldehyde, and/or ninhydrin staining. Prepara-
tive TLC was also performed with E. Merck Brinkman plates
of the appropriate thickness. Flash silica gel chromatography
was performed with ICN silica, 32-63 mesh, purchased from
Bodman. Columns were eluted with a linear gradient by
loading the compound in CH2Cl2 on to silica with 100%
nonpolar eluent and gradually increasing the polarity. Unless
otherwise noted, columns and TLCs were eluted with hexanes
and EtOAc. Crude compounds 7-18 were plated on a mini-
mum amount of silica and loaded directly on the column. For
these compounds IR spectra were not taken due to probable
contamination with KBr, which may impede biological evalu-
ation of them. NMR spectra were obtained on 500, 400, or
and the reaction was allowed to stir for another 30 min.
A
majority of the THF was evaporated, and the reaction was
diluted with 200 mL of CH2Cl2, quenched with saturated NH4-
Cl, and extracted with CH2Cl2 (3 × 200 mL); TLC in 2/1 Hex/
EtOAc. Chromatography on silica gel gave 9.6 g of 22 (87%).
IR (neat): υmax 3304, 2996, 2946, 1669, 1516, 1374, 1198, 1117,
1051, 855 cm-1 1H NMR (400 MHz, CDCl3): δ 7.32 (m, 5H),
.
6.13 (dd, 1H, J ) 9.4, 10.3 Hz), 5.92 (d, 1H, J ) 9.6 Hz), 4.86
(d, 1H, J ) 3.7 Hz), 4.69 (d, 1H, J ) 12.0 Hz), 4.47 (d, 1H, J
) 12.1 Hz), 4.43 (ddd, 1H, J ) 3.8, 10.4, 10.4 Hz), 3.92 (m,
1H), 3.77 (m, 3H), 2.48 (s, 3H), 1.82 (s, 3H), 1.44 (s, 3H), 1.34
(s, 3H). 13C NMR (90 MHz, CDCl3): δ 217.2, 169.7, 136.4,
128.3, 128.0, 127.8, 99.6, 97.1, 78.6, 72.0, 69.6, 63.9, 62.0, 52.5,
28.7, 22.9, 18.7, 18.8. HRMS (FAB): M + H calcd 442.1358,
found 442.1358.
Ben zyl 3-Allyl-4,6-isop r op ylid en e-N-a cetyl-r-D-glu co-
sid e. The benzyl 4,6-isopropylidene-3-((methylthio)thiocar-
bonyl)-N-acetyl-R-D-glucoside (22) (29.0 g, 66.0 mmol), allyl-
tributyltin hydride (50 mL), and AIBN (0.80 g, 6.6 mmol) were
dissolved in 80 mL of toluene under N2 and refluxed. After 8
h TLC showed starting material, and more AIBN was admitted
to the reaction which was allowed to stir 4 h more at which

5276 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
time all of the starting material had disappeared and the
excess toluene was evaporated (the product has an Rf just
slightly higher than the starting material in 33% EtOAc/
hexanes). The crude mixture was taken up in EtOAc and brine
and extracted. The product was purified by flash silica gel
chromatography twice to give a yellow oil of which 11.3 g was
olefinic product (46%). IR (neat): 3304, 2942, 2913, 1647,
tions with CH2Cl2 (3 × 15 mL) the two diastereomers were
separated on silica gel (TLC in 3/1 Hex/EtOAc) to yield a major
and minor compound: total weight 162.8 mg (91%), 37.3 mg
of the minor diastereomer 23 (eluted first), 18.5 mg of a
mixture, and 107.0 mg of the major diastereomer 24 (eluted
second). Com p ou n d 23. IR (neat): 2926, 2857, 1661, 1512,
1497, 1455, 1377, 1258, 1204, 1115, 1074, 698 cm-1 1H NMR
.
1541, 1375, 1198, 1125, 1069, 1047 cm-1
.
1H NMR (360 MHz,
(500 MHz, CDCl3): δ 7.30 (m, 20H), 5.69 (d, 1H, J ) 8.9 Hz),
5.02 (s, 1H), 4.89 (s, 1H), 4.82 (d, 1H, J ) 3.5 Hz), 4.73 (d, 1H,
J ) 11.9 Hz), 4.71 (d, 1H, J ) 11.9 Hz), 4.67 (d, 1H, J ) 12.1
Hz), 4.60 (d, 1H, J ) 11.8 Hz), 4.58 (d, 1H, J ) 11.8 Hz), 4.53
(d, 1H, J ) 11.6 Hz), 4.42 (d, 1H, J ) 11.8 Hz), 4.23 (m, 1H),
4.18 (m, 1H), 3.92 (m, 1H), 3.88-3.80 (m, 2H), 3.36 (dd, 1H, J
) 9.1, 9.1 Hz), 2.31 (dd, 1H, J ) 4.0, 14.5 Hz), 2.18 (dd, 1H, J
) 9.3, 14.5 Hz), 2.01 (m, 1H), 1.89 (s, 3H), 1.59 (m, 1H), 1.38
(s, 3H), 1.32 (s, 3H), 0.93 (d, 3H, J ) 6.4 Hz), 0.86 (s, 9H),
0.03 (s, 3H), 0.01 (s, 3H). 13C NMR (100.6 MHz, CDCl3): δ
169.8, 149.5, 138.7, 138.6, 138.4, 137.4, 128.4, 128.3, 128.2,
127.9, 127.8, 127.6, 127.5, 127.5, 127.4, 110.5, 99.3, 96.5, 75.9,
75.6, 75.0, 73.0, 69.5, 68.4, 65.4, 62.8, 52.3, 36.8, 36.0, 29.1,
26.0, 23.2, 19.0, 18.1, 15.3, -4.3, -4.9. HRMS (FAB): M + H
calcd 950.5239, found 950.5235. Com p ou n d 24. IR (neat):
CDCl3): δ 7.27 (m, 5H), 6.06 (d, 1H, J ) 9.8 Hz), 5.81 (m, 1H),
5.16 (m, 2H), 4.70 (d, 1H, J ) 3.6 Hz), 4.67 (d, 1H, J ) 11.9
Hz), 4.39 (d, 1H, J ) 11.9 Hz), 4.12 (m, 1H), 3.77 (m, 1H),
3.66 (m, 2H), 3.42 (dd, 1H, J ) 10.1, 10.1 Hz), 2.26 (ddd, 1H,
J ) 4.7, 9.0, 14.0 Hz), 2.13 (dt, 1H, J ) 5.2, 13.9 Hz), 1.97 (m,
1H), 1.87 (s, 3H), 1.42 (s, 3H), 1.38 (s, 3H). 13C NMR (90 MHz,
CDCl3): δ 169.4, 137.0, 134.1, 128.2, 127.7, 127.7, 117.4, 99.1,
96.3, 70.5, 69.1, 64.6, 62.6, 49.5, 39.0, 29.6, 28.9, 22.6, 20.7,
18.7. HRMS (FAB): M + H calcd 376.2124, found 376.2115.
[R]D ) +72.6° (c 0.0117, CH2Cl2).
Com p ou n d 20. A solution of benzyl 3-allyl-4,6-isopropyl-
idene-N-acetyl-R-D-glucoside (8.6 g, 22.9 mmol) in 200 mL of
CH2Cl2 was brought to -78 °C. Ozone was bubbled through
the solution until a sky blue color persisted. After ozonide
formation was complete by TLC, tributylphosphine (8.63 mL,
34.6 mmol) was added to the stirring solution, which was
allowed to slowly warm to room temperature. TLC (2/1 Hex/
EtOAc) confirmed conversion of ozonide to product and the
solvent was evaporated. The product was purified by flash
silica gel chromatography to give 20, 6.0 g (69% yield, a higher
yield of 89% was obtained on a smaller scale) of a yellow oil.
IR (neat): 2940, 1723, 1661, 1539, 1373, 1267, 1202, 1136,
2928, 1672, 1537, 1454, 1372, 1117, 1071, 698 cm-1 1H NMR
.
(500 MHz, CDCl3): δ 7.35-7.15 (m, 21H), 5.02 (d, 1H, J ) 1.8
Hz), 4.97 (d, 1H, J ) 10.9 Hz), 4.91 (s, 1H), 4.84 (d, 1H, J )
11.9 Hz), 4.70 (m, 3H), 4.70 (m, 2H), 4.58 (d, 1H, J ) 11.9
Hz), 4.46 (d, 1H, J ) 10.9 Hz), 4.39 (d, 1H, J ) 11.9 Hz), 4.33
(m, 1H), 4.07 (m, 1H), 3.80-3.67 (m, 6H), 3.60 (d, 1H, J ) 2.4
Hz), 4.43 (dd, 1H, J ) 9.5, 9.5 Hz), 2.87 (dd, 1H, J ) 2.8,14.3
Hz), 2.31 (t, 1H, J ) 13.2 Hz), 1.55 (s, 3H), 1.43 (s, 3H), 1.41
(s, 3H), 1.40 (m, 1H), 0.93 (d, 3H, J ) 6.4 Hz), 0.87 (s, 9H),
0.03 (s, 3H), 0.01 (s, 3H). 13C NMR (125.7 MHz, CDCl3): δ
170.8, 145.8, 138.8, 138.7, 138.3, 137.4, 128.4, 128.3, 128.3,
128.2, 128.1, 128.0, 127.7, 127.7, 127.6, 127.5, 127.5, 127.3,
117.1, 99.0, 95.8, 79.3, 78.1, 75.5, 75.4, 75.0, 72.9, 72.8, 71.8,
69.3, 67.4, 64.8, 62.8, 51.6, 39.2, 34.5, 29.3, 28.6, 25.9, 22.0,
19.0, 18.4, 16.6, -4.9, -5.0. HRMS (FAB): M + H calcd
950.5239, found 950.5240. [R]D ) +25.3° (c 0.0119, CH2Cl2).
Com p ou n d 25. The TBS ether 24 (333 mg, 0.351 mmol)
was dissolved in 10 mL of THF and cooled to 0 °C. A 0.5 M
solution of 9-BBN in hexanes (1.75 mmol) was added dropwise,
and the solution was allowed to stir for 0.5 h and then for 1 h
at room temperature. The reaction was recooled to 0 °C and
quenched with successive addition of 1 mL of EtOH, 4 mL of
a pH 7 phosphate buffer, and 1.5 mL of 30% H2O2. The
reaction was warmed to room temperature and stirred for 2 h
at which time the flask was diluted with brine and extracted
with EtOAc (3 × 30 mL). The product was purified by flash
silica gel chromatography (TLC in 2/1 Hex/EtOAc) to give a
yellow oil, 188 mg (55%). IR (neat): 3438, 2928, 2857, 1663,
1076, 1042, 854, 737 cm-1
.
1H NMR (360 MHz, CDCl3): δ 9.58
(t, 1H, J ) 1.7 Hz), 7.33 (m, 5H), 6.16 (d, 1H, J ) 9.7 Hz),
4.82 (d, 1H, J ) 3.6 Hz), 4.67 (d, 1H, J ) 11.9 Hz), 4.42 (d,
1H, J ) 11.9 Hz), 3.71 (ddd, 1H, J ) 3.0, 8.1, 11.4 Hz), 4.04
(ddd, 1H, J ) 2.7, 9.6, 14.5 Hz), 3.66 (m, 1H), 3.39 (dd, 1H, J
) 9.1, 9.1 Hz), 2.49 (m, 1H), 2.36 (dd, 1H, J ) 6.9, 11.9 Hz),
1.83 (s, 3H), 1.39 (s, 3H), 1.31 (s, 3H). 13C NMR (90.5 MHz,
CDCl3): contaminant from triphenylphosphine oxide δ 201.2,
169.9, 136.8, 132.7, 131.9, 131.7, 131.6, 128.3, 128.3, 128.2,
127.9, 127.8, 99.4, 96.1, 72.3, 69.3, 64.9, 62.4, 51.6, 42.8, 35.9,
28.8, 22.8, 18.8. HRMS (FAB): M + H calcd 378.1917, found
378.1915. [R]D ) +70.8° (c 0.0154, CH2Cl2).
Com p ou n d s 23 a n d 24. A 0.5% NiCl2/CrCl2 mixture (300
mg, 2.4 mmol) was heated to 180 °C in a sand bath under
vacuum for 3+ days. Once the mixture had turned a grayish
green it was cooled and vented to N2. A separate flask
containing aldehyde 20 (150 mg, 0.4 mmol) and vinyl bromide
19 (650 mg, 1.2 mmol) was azeotroped on a high-vacuum line
with distilled toluene, venting to N2. In a glovebox, a solution
of aldehyde and vinyl bromide in 3 mL of 4:1 THF:DMF was
transferred to the flask containing the chromium. After 2 days
all of the aldehyde had been consumed and the reaction was
quenched with 10 mL of saturated NH4Cl; TLC in 2/1 Hex/
EtOAc. Extractions with EtOAc (3 × 20 mL) gave an oil that
was purified by flash silica gel chromatography to give a 2:1
mixture of allylic alcohol diastereomers, 240 mg (72%). IR
(neat): 3351, 2926, 1725, 1655, 1453, 1269, 1167, 1071, 713
1
1455, 1454, 1379, 1262, 1202, 1119, 1069, 1028, 698 cm-1. H
NMR (400 MHz, CDCl3): δ 7.31 (m, 20H), 5.51 (d, 1H, J ) 9.7
Hz), 4.83-4.41 (m, 10H), 4.12-3.60 (m, 14H), 3.48 (m, 2H),
3.40 (dd, 1H, J ) 9.6, 9.6 Hz), 1.94 (m, 1H), 1.88 (s, 3H), 1.87-
1.57 (m, 4H), 1.48(s, 3H), 1.39 (s, 3H), 1.20 (d, 3H, J ) 8.5
Hz), 0.83 (s, 9H), 0.08 (s, 3H), 0.05 (s, 3H). 13C NMR (100.6
MHz, CDCl3): δ 169.9, 138.5, 138.4, 138.1, 137.0, 128.4, 128.4,
128.3, 128.2, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5,
127.4, 127.3, 99.4, 96.2, 77.8, 76.0, 75.2, 74.8, 73.4, 73.4, 72.9,
72.8, 69.4, 64.4, 62.6, 60.3, 52.5, 36.1, 33.4, 29.0, 25.8, 25.8,
23.0, 18.9, 17.8, 17.7, 15.5, 14.1, -4.3, -4.6. HRMS (FAB):
M + H calcd 968.5344, found 968.5364. [R]D ) +31.7° (c
0.0820, CDCl3).
cm-1 1H NMR (500 MHz, CDCl3): δ 7.29 (m, 20H), 5.09 (s,
.
1H), 4.95 (s, 1H), 4.91-4.42 (m, 9H), 4.23-4.05 (m, 2H), 3.89
(m, 2H), 3.79 (m, 1H), 3.71 (m, 3H), 2.34 (d, 1H, J ) 5.3 Hz),
1.76 (s, 3H), 1.58 (m, 4H), 2.10-1.89 (m, 1H), 1.49 (s, 3H), 1.41
(s, 3H); major diastereomer 6.30 (d, 1H, J ) 8.8 Hz), 3.40 (t,
1H, J ) 3.7 Hz), 1.15 (d, 3H, J ) 6.5 Hz); minor diastereomer
6.00 (d, 1H, J ) 9.2 Hz), 4.80 (d, 1H, J ) 3.2 Hz), 1.20 (d, 3H,
J ) 6.5 Hz). 13C NMR (100.6 MHz, CDCl3): δ 170.0, 170.5,
148.4, 148.2, 138.4, 138.4, 138.1, 137.1, 128.3, 128.2, 128.2,
128.2, 128.0, 128.0, 128.0, 127.9, 127.9, 127.8, 127.7, 127.4,
127.4, 127.2, 127.2, 113.0, 112.5, 99.6, 99.4, 95.9, 95.9, 74.5,
73.2, 72.9, 72.8, 72.7, 72.0, 69.3, 69.2, 64.8, 64.8, 62.5, 51.6,
38.0, 35.6, 35.5, 28.9, 28.9, 22.6, 22.6, 18.9, 15.3. HRMS
(FAB): M + H calcd 836.4374, found 836.4384.
To a solution of the alcohol (17.6 mg, 0.018 mmol) in 1 mL
of CH2Cl2 was added a freshly prepared solution of Dess-
Martin periodinane (DMP, 39 mg, 0.091 mmol) in 0.5 mL of
CH2Cl2. This solution was prepared by stirring the DMP with
0.5 mL of CH2Cl2 and one drop of pyridine for 20 min. The
reaction was finished after 2 h and was quenched with 2 mL
of 1.5 M sodium thiosulfate and 2 mL of saturated NaHCO3.
After the aqueous layer was extracted with CH2Cl2 (3 × 20
mL), the product was purified on silica gel (TLC in 2/1 Hex/
EtOAc) to give 25, 16.6 mg (97%). IR (neat): 2930, 2859, 1719,
1682, 1497, 1454, 1373, 1260, 1207, 1117, 1071, 1047, 1028,
To a solution of the allylic alcohol (158 mg, 0.189 mmol) in
4.5 mL of CH2Cl2, at 0 °C, was added 2,6-lutidine (44.0 µL,
0.379 mmol) followed by TBSOTf (53.0 µL, 0.227 mmol). After
0.5 h the reaction was warmed to room temperature and
quenched with 5 mL of saturated NaHCO3. Following extrac-
735, 698 cm-1
.
1H NMR (400 MHz, CDCl3): δ 9.76 (d, 1H, J
) 1.52 Hz), 7.31 (m, 20H), 5.62 (d, 1H, J ) 9.6 Hz), 4.85 (d,

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5277
1H, J ) 11.7 Hz), 4.72 (m, 6H), 4.60 (d, 1H, J ) 11.6 Hz), 4.43
(d, 1H, J ) 11.8 Hz), 4.17 (m, 4H), 3.98 (m, 1H), 2.58 (b, 1H),
2.16 (m, 1H), 1.92 (m, 1H), 1.86 (s, 3H), 1.73 (m, 1H), 1.61 (m,
2H), 1.43 (s, 3H), 1.34 (s, 3H), 1.11 (d, 3H, J ) 6.3 Hz), 0.82
(s, 9H), 0.06 (s, 3H), 0.01 (s, 3H). 13C NMR (100.6 MHz,
CDCl3): δ 203.4, 169.9, 138.6, 138.5, 128.5, 128.4, 128.3, 128.3,
128.2, 128.2, 128.1, 128.0, 128.0, 127.7, 127.7, 127.5, 127.5,
127.4, 99.4, 96.3, 74.9, 73.4, 72.9, 70.5, 69.5, 65.2, 62.6, 54.0,
52.0, 36.1, 29.0, 25.8, 25.7, 23.1, 18.9, 17.8, -4.2, -4.6. HRMS
(FAB): M + H calcd 966.5188, found 966.5190.
and a crude 1H NMR confirmed oxidation of the homoallylic
alcohol. The resultant ketone was dissolved in 900 µL of THF
and treated with an excess of a 2.0 M LiBH4 solution (200 µL,
0.400 mmol) at 0 °C. After TLC showed disappearance of all
of the starting ketone, the reaction was quenched with 5 mL
of a saturated solution of NH4Cl and extracted with CH2Cl2
(4 × 20 mL). Preparatory TLC in 2/1 Hex/EtOAc was
performed (20 cm × 20 cm plate, 0.25 mm thick) to yield 6.0
mg of a minor compound (eluted first) and 15.0 mg of a major
compound (eluted second) that spectroscopically match the
diastereomers created in the nonasymmetric allylation, 95%
total yield.
Com p ou n d 28. The TBS-protected homoallylic alcohol 26
(51 mg, 0.051 mmol) in 400 µL of Et2O was cooled to 0 °C. A
1.0 M solution of TBAF (0.100 mmol) was added and the
reaction stirred for 1 h. The solvent was evaporated and the
oil was purified with silica gel chromatography (TLC in 1/1
Com p ou n d s 26 a n d 27. To a stirred solution of aldehyde
25 (41 mg, 0.043 mmol) in 1.7 mL of THF cooled to -78 °C
was added a 1.0 M solution of allylmagnesium bromide (0.127
mmol, Aldrich). After 0.5 h of continued stirring, the reaction
was quenched with saturated ammonium chloride and ex-
tracted with excess CH2Cl2. The two resultant diastereomers
were separated on silica gel (TLC in 2/1 Hex/EtOAc) to yield
major (26) and minor (27) compounds in a 1:2 ratio, total
weight 37.3 mg (88%). Com p ou n d 26. IR (neat): 3449, 2924,
Hex/EtOAc) to yield 44 mg of 28 (97%). IR (neat): υmax
2924, 1655, 1541, 1497, 1455, 1375, 1204, 1119, 1069, 1039,
698 cm-1 1H NMR (500 MHz, CDCl3): δ 7.32 (m, 20H), 6.01
3341,
2857, 1742, 1684, 1530, 1456, 1377, 1350, 1254, 1115 cm-1
.
.
1H NMR (500 MHz, CDCl3): δ 7.30 (m, 1H), 6.06 (d, 1H, J )
9.2 Hz), 5.82 (m, 1H), 5.06 (m, 2H), 4.85 (d, 1H, J ) 11.7 Hz),
4.73-4.61 (m, 6H), 4.55 (d, 1H, J ) 11.7 Hz), 4.39 (d, 1H, J )
11.8 Hz), 4.21 (m, 1H), 4.14 (m, 1H), 4.08-3.98 (m, 3H), 3.88
(b, 1H), 3.80 (dt, 2H, J ) 3.0, 8.5 Hz), 3.67 (m, 4H), 3.32 (dd,
1H, J ) 9.3, 9.3 Hz), 2.34 (dt, 1H, J ) 7.4, 14.5 Hz), 2.15 (m,
1H), 2.04 (m, 1H), 1.84 (s, 3H), 1.77 (m, 2H), 1.68 (b, 1H), 1.61
(bd, 1H, J ) 9.3 Hz), 1.48 (s, 3H), 1.42 (s, 3H), 1.04 (d, 3H, J
) 6.2 Hz), 0.80 (s, 9H), 0.05 (s, 3H), -0.02 (s, 3H). 13C NMR
(125.7 MHz, CDCl3): δ 169.9, 138.8, 138.5, 138.3, 137.0, 135.7,
128.4, 128.4, 128.2, 128.2, 128.0, 127.7, 127.6, 127.5, 127.5,
116.7, 99.7, 95.9, 78.7, 76.6, 76.3, 73.8, 73.8, 73.2, 72.9, 71.6,
69.9, 69.4, 69.3, 68.2, 65.1, 62.7, 53.5, 38.8, 36.1, 33.9, 29.2,
25.8, 22.7, 19.1, 17.7, 16.0, -3.9, -4.8. HRMS (FAB): M + H
calcd 1008.5657, found 1008.5662. [R]D ) +24.0° (c 0.0095,
CDCl3). Com p ou n d 27. IR (neat): 3440, 2928, 2665, 1530,
(d, 1H, J ) 9.2 Hz), 5.78 (m, 1H), 5.07 (m, 2H), 4.80 (d, 1H, J
) 3.5 Hz), 4.78 (d, 1H, J ) 12.0 Hz), 4.72 (d, 1H, J ) 12.0 Hz),
4.71 (d, 1H, J ) 11.6 Hz), 4.68 (d, 1H, J ) 11.8 Hz), 4.65 (d,
1H, J ) 11.7 Hz), 4.59 (d, 1H, J ) 11.8 Hz), 4.57 (d, 1H, J )
11.6 Hz), 4.45 (d, 1H, J ) 11.9 Hz), 4.15 (m, 1H), 4.05 (t, 1H,
J ) 6.2 Hz), 3.97 (m, 2H), 3.86 (b, 2H), 3.80 (m, 1H), 3.75 (m,
2H), 3.69 (m, 2H), 3.44 (dd, 1H, J ) 9.7, 9.7 Hz), 3.38 (b, 1H),
3.29 (b, 1H), 2.29 (m, 1H), 2.13 (m, 1H), 2.03 (m, 1H), 1.87 (s,
3H), 1.75 (m, 4H), 1.53 (b, 1H), 1.42 (s, 3H), 1.32 (s, 3H), 1.21
(d, 3H, J ) 6.8 Hz).
13C NMR (125.7 MHz, CDCl3): δ 170.1,
138.7, 138.5, 138.2, 137.2, 135.3, 128.5, 128.4, 128.3, 128.2,
128.1, 128.0, 127.9, 127.8, 128.6, 127.5, 127.5, 117.3, 99.6, 96.3,
76.1, 74.3, 73.3, 73.0, 71.4, 70.6, 69.6, 68.4, 65.1, 62.7, 52.3,
42.1, 38.9, 36.9, 34.8, 29.7, 29.1, 23.0, 19.1, 15.6 ppm. HRMS
(FAB): M + H calcd 894.4792, found 894.4810. [R]D
(c 0.0078, CHCl3).
) +23.0°
1350, 1070, 1044, 733, 698 cm-1 1H NMR (500 MHz, CDCl3):
.
Com p ou n d s 12 a n d 13. 28 (15 mg, 0.0168 mmol) was
combined with MCPBA (11.6 mg, 0.0673 mmol) and NaH2PO4
(16.0 mg, 0.135 mmol) in 2 mL of CH2Cl2, and the solution
was stirred for 24 h sealed with a glass stopper. The reaction
was quenched with 10 mL of brine and extracted with CH2Cl2
(4 × 15 mL) to yield an inseparable mixture of epoxide
diastereomers that was isolated with silica gel chromatography
(5% MeOH in CH2Cl2), 9.4 mg (63%). IR (neat): υmax 3339,
2923, 2853, 1727, 1655, 1539, 1454, 1377, 1267, 1206, 1119,
δ 7.31 (m, 20H), 5.87 (m, 1H), 5.68 (d, 1H, J ) 9.2 Hz), 5.10
(m, 2H), 4.79 (d, 1H, J ) 1.6 Hz), 4.75-4.55 (m, 10H), 4.41 (d,
1H, J ) 11.7 Hz), 4.10 (m, 1H), 4.02 (m, 1H), 3.92 (m, 4H),
3.84-3.68 (m, 6H), 3.43 (dd, 1H, J ) 9.0, 9.0 Hz), 2.33 (m,
1H), 2.26 (m, 1H), 1.96 (m, 1H), 1.85 (m, 1H), 1.79 (s, 3H),
1.74 (m, 2H), 1.64 (br, 2H), 1.48 (s, 3H), 1.40 (s, 3H), 1.24 (d,
3H, J ) 6.7 Hz), 0.82 (s, 9H), 0.05 (s, 3H), -0.01 (s, 3H). 13C
NMR (125.7 MHz, CDCl3): δ 169.7, 138.6, 138.1, 137.3, 136.4,
128.4, 128.3, 128.3, 128.3, 128.1, 128.0, 127.9, 127.8, 127.7,
127.7, 127.6, 127.5, 116.6, 99.5, 96.3, 75.0, 73.4, 73.1, 73.0, 71.4,
69.5, 68.8, 65.3, 62.7, 52.6, 38.7, 35.7, 29.2, 26.1, 26.0, 26.0,
22.9, 19.1, 17.9, 15.3, -4.1, -4.2. HRMS (FAB): M + H calcd
1008.5657, found 1008.5648.
Asym etr ic Rou te to Com p ou n d 26. (+)-Ipc2BOMe (50
mg, 0.155 mmol) was dissolved in 0.5 mL of THF, and the
solution was cooled to -78 °C. A 1.0 M solution of allylmag-
nesium bromide (0.110 mmol, Aldrich) was added slowly to
the reaction. After the solution was stirred for 1 h, the cold
bath was removed and the reaction was warmed to room
temperature, allowed to stir for an additional 15 min, and then
recooled to -78 °C. Aldehyde 25 (50 mg, 0.052 mmol) was
added to 300 µL of THF. The reaction was stirred at -78 °C
for 6 h and was then allowed to slowly warm to room
temperature over 12 h. At this time 200 µL of 3 N NaOH and
200 µL of 30% H2O2 were added, and the reaction was stirred
for an additional 3 h. The reaction was diluted with 5 mL of
brine and extracted with CH2Cl2 (4 × 25 mL). The solvent
was evaporated and chromatographed on silica (TLC in 2/1
Hex/EtOAc) to give 22.1 mg of a major compound (eluted first)
and 3.7 mg of a minor compound (eluted second) that spec-
troscopically match the diastereomers created in the nonasym-
metric allylation, 48% total yield.
1071, 1041, 735, 695 cm-1 1H NMR (500 MHz, CDCl3): δ 7.28
.
(m, 40H), 6.08 (d, 1H, J ) 9 Hz), 6.04 (d, 1H, J ) 9 Hz), 4.80-
4.45 (m, 20H), 4.27 (bd, 1H), 4.22 (bd, 1H), 4.14 (m, 1H), 4.08
(m, 1H), 4.03-3.82 (m, 2H), 3.80-3.63 (m, 16H), 3.45 (dt, 3H,
J ) 1.8, 8.9 Hz), 3.07 (m, 2H), 2.78 (t, 1H, J ) 4.7 Hz), 2.73 (t,
1H, J ) 4.7 Hz), 2.51 (m, 2H), 2.05 (m, 4H), 1.89 (s, 6H), 1.42
(s, 3H), 1.32 (s, 3H), 1.25 (s, 6H), 1.25 (d, 3H, J ) 5.9 Hz),
1.21 (d, 3H, J ) 6.4 Hz). 13C NMR (125.7 MHz, CDCl3): δ
170.2, 138.6, 138.5, 138.4, 138.4, 138.2, 138.1, 137.1, 128.4,
128.3, 128.3, 128.3, 128.2, 128.2, 128.0, 128.0, 127.9, 127.8,
127.7, 127.7, 127.5, 127.5, 127.4, 127.4, 99.6, 99.5, 96.3, 96.2,
74.3, 74.2, 73.3, 73.0, 71.2, 69.6, 69.4, 68.9, 68.7, 65.0, 65.0,
62.6, 52.0, 50.5, 50.3, 47.0, 46.6, 43.4, 42.9, 36.7, 36.6, 34.8,
29.6, 29.0, 22.9, 19.0. HRMS (FAB): M + H calcd 910.4742,
found 910.4754.
The epoxide from 28 (9.3 mg, 10.2 µmol) was dissolved in 1
mL of CH2Cl2 and stirred overnight with CSA (1.2 mg, 5 µmol).
The reaction was then quenched with 10 mL of saturated
NaHCO3 and extracted with CH2Cl2 (3 × 25 mL). The crude
(9-10 mg) was taken directly on to the hydrogenation reaction
listed below; TLC in 5% MeOH/CH2Cl2. IR (neat): υmax 3403,
2925, 1656, 1528, 1350, 1047, 733, 698 cm-1
.
1H NMR (500
MHz, CDCl3): δ 7.32 (m, 40H), 5.61 (d, 1H, J ) 9.0 Hz), 5.49
(d, 1H, J ) 9.0 Hz), 4.82-4.41 (m, 18H), 4.08 (m, 1H), 4.06
(m, 1H), 3.98 (m, 5H), 3.90-3.59 (m, 19H), 3.53 (m, 2H), 3.44
(m, 1H), 3.31 (m, 1H), 2.04 (m, 4H), 1.87-1.43 (m, 12H), 1.75
(s, 3H), 1.66 (s, 3H), 1.25 (m, 6H). HRMS (FAB): (M -
C7H7O)+ calcd 762.3853, found 762.3862.
The crude from the CSA cyclization (9-10 mg) was dissolved
in 2 mL of dry MeOH. This was stirred with 9 mg of Pd(OH)2
on carbon under a H2 atmosphere until all starting material
Asym m etr ic Rou te to Com p ou n d 27. 26 (22.1 mg, 0.024
mmol) was dissolved in 0.5 mL of CH2Cl2, treated with a 0.5
mL solution of CH2Cl2 containing Dess-Martin periodinane
(20 mg, 0.047 mmol), and allowed to stir for 1 h. The reaction
was quenched with 3 mL of 1.5 M sodium thiosulfate and 3
mL of saturated NaHCO3. After the aqueous layer was
extracted with CH2Cl2 (3 × 20 mL), the solvent was evaporated

5278 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
was consumed. The solvent was filtered through a bed of
Celite, isolating the carbon bound Pd(OH)2. The MeOH was
evaporated, and the oil was chromatographed on silica gel
(linear gradient 0-20% MeOH/CH2Cl2) to yield inseparable
polyols 12 and 13, 5.2 mg (87% from the epoxide). 1H NMR
(500 MHz, CD3OD): δ 7.32 (m, 10H), 4.76 (d, 2H, J ) 21.1
Hz), 4.72 (d, 1H, J ) 3.0 Hz), 4.51 (d, 2H, J ) 12.1 Hz), 4.09
(m, 1H), 4.03 (m, 2H), 3.97 (m, 1H), 3.92-3.73 (m, 8H), 3.68-
3.59 (m, 10H), 3.55-3.44 (m, 6H), 2.24 (bt, 1H, J ) 12.2 Hz),
2.15 (b, 2H), 1.95 (s, 3H), 1.95 (s, 3H), 1.87 (m, 2H), 1.81 (m,
1H), 1.74-1.57 (m, 8H), 1.53 (m, 1H), 1.48 (m, 1H), 1.22 (d,
3H, J ) 6.8 Hz), 1.20 (d, 3H, J ) 7.5 Hz). HMQC with a BIRD
pulse (500 × 125 MHz, CD3OD) indicates the following 13C
resonances: δ 129.0, 128.4, 96.2, 96.1, 80.2, 80.0, 75.2, 74.6,
74.6, 73.4, 73.0, 72.1, 71.7, 70.9, 70.8, 69.6, 69.6, 69.8, 69.5,
69.1, 68.6, 65.8, 65.8, 64.2, 64.2, 62.7, 62.7, 52.4, 52.0, 49.7,
47.8, 44.0, 39.2, 37.2, 33.2, 33.0, 32.9, 30.5, 26.1, 24.9, 24.7,
22.3, 16.1. HRMS (FAB): M + H calcd 600.3020, found
600.3020.
3H), 3.83 (m, 2H), 3.74 (m, 1H), 3.71-3.60 (m, 3H), 3.56 (dd,
1H, J ) 3.5, 11.4 Hz), 3.44 (dd, 1H, J ) 6.8, 11.4 Hz), 1.95 (s,
3H), 1.79 (dd, 1H, J ) 4.9, 15.3 Hz), 1.75 (m, 1H), 1.68 (m,
1H), 1.59 (m, 2H), 1.53 (m, 1H), 1.45 (m, 1H), 1.22 (d, 3H,
J ) 6.5 Hz). F r a ction 3, com p ou n d 15. 1H NMR (500 MHz,
CD3OD): δ 7.34 (m, 5H), 4.76 (d, 1H, J ) 12.0 Hz), 4.71 (d,
1H, J ) 3.3 Hz), 4.51 (d, 1H, J ) 12.2 Hz), 4.10 (m, 2H), 3.97
(dd, 1H, J ) 3.3, 12.2 Hz), 3.92 (m, 2H), 3.80 (m, 3H), 3.62 (m,
5H), 3.55 (m, 1H), 2.21 (m, 1H), 1.95 (s, 3H), 1.89 (m, 1H),
1.73 (m, 2H), 1.59 (m, 3H), 1.44 (m, 1H), 1.16 (d, 3H, J ) 6.4
Hz). HMQC with a BIRD pulse (500 × 125 MHz, CD3OD)
indicates the following 13C resonances: δ 129.1, 69.2, 74.4,
73.8, 71.6, 70.7, 70.5, 70.3, 69.5, 69.3, 67.8, 66.4, 66.1, 62.8,
62.7, 51.6, 41.0, 32.9, 30.3, 30.1, 22.1, 20.0, 16.6. HRMS
(FAB): M + H calcd 600.3020, found 600.3021.
Com p ou n d 30. 27 (21 mg, 0.021 mmol) was dissolved in
0.5 mL of CH2Cl2 and cooled to 0 °C. The reaction was treated
with 2,6-lutidene (10 µL, 0.084 mmol) and then with TBSOTf
(12 µL, 0.050 mmol). After the solution was stirred for 0.5 h,
the reaction was warmed to room temperature, quenched with
2 mL of saturated NH4Cl, and extracted with CH2Cl2 (4 × 25
mL). Silica gel chromatography (TLC in 2/1 Hex/EtOAc) gave
20 mg of the bis-TBS ether (85%). IR (neat): 3353, 2928, 1682,
Com p ou n d 29. The TBS-protected homoallylic alcohol 27
(14.0 mg, 0.0139 mmol) in 0.70 mL of THF was cooled to 0 °C.
A 1.0 M solution of TBAF (0.021 mmol) was added and the
reaction stirred for 1 h. The solvent was evaporated, and the
oil was purified with silica gel chromatography (TLC 1/1 Hex/
EtOAc) to yield 9 mg of 29 (72%). IR (neat): 3425, 2924, 2855,
1659, 1653, 1539, 1497, 1454, 1377, 1265, 1206, 1118, 1072,
1456, 771, 1256, 1047 cm-1
.
1H NMR (500 MHz, CDCl3): δ
7.31 (m, 20H), 5.79 (m, 1H), 5.02 (d, 1H, J ) 6.5 Hz), 4.97 (d,
1H, J ) 10.2 Hz), 4.93 (d, 1H, J ) 11.0 Hz), 4.69 (m, 5H), 4.62
(d, 1H, J ) 11.6 Hz), 4.53 (d, 1H, J ) 11.7 Hz), 4.39 (d, 1H, J
) 11.6 Hz), 4.21 (t, 1H, J ) 7.8 Hz), 4.12 (m, 2H), 3.99 (m,
2H), 3.81 (m, 3H), 3.71 (m, 4H), 3.53 (b, 1H), 3.33 (dd, 1H, J
) 8.3, 8.3 Hz), 2.12 (b, 2H), 1.98 (m, 2H), 1.86 (s, 3H), 1.71
(m, 4H), 1.49 (s, 3H), 1.43 (s, 3H), 1.29 (m, 4H), 0.82 (s, 9H),
0.80 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H), -0.01 (s,
3H). 13C NMR (125 MHz, CDCl3): δ 170.0, 139.1, 138.6, 138.5,
137.0, 128.6, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8,
127.6, 127.5, 127.4, 127.3, 99.7, 96.1, 74.0, 72.8, 69.5, 65.0, 62.8,
39.2, 35.6, 29.7, 29.4, 26.2, 26.0, 25.9, 22.6, 19.1, 18.0, 17.9,
-3.9, -4.0, -4.0, -4.4. HRMS (FAB): M + H calcd 1122.6522,
found 1122.6525. [R]D ) +0.5° (c 0.020, CH2Cl2).
1042, 735, 698 cm-1
.
1H NMR (500 MHz, CDCl3): δ 7.32 (m,
20H), 6.06 (d, 1H, J ) 9.1 Hz), 5.84 (m, 1H), 5.08 (m, 2H),
4.82 (d, 1H, J ) 3.6 Hz), 4.76 (d, 1H, J ) 13.0 Hz), 4.71 (d,
1H, J ) 11.6 Hz), 4.67 (m, 2H), 4.63 (d, 1H, J ) 11.7, Hz),
4.57 (d, 1H, J ) 11.7 Hz), 4.54 (d, 1H, J ) 11.8 Hz), 4.45 (d,
1H, J ) 11.8 Hz), 4.06 (m, 1H), 3.92 (m, 2H), 3.80 (m, 4H),
3.71 (m, 4H), 3.45 (dd, 1H, J ) 9.0, 9.0 Hz), 2.35 (m, 1H), 2.18
(m, 1H), 2.06 (m, 2H), 1.82 (s, 3H), 1.73-1.52 (m, 8H), 1.43 (s,
3H), 1.37 (s, 3H), 1.23 (d, 3H, J ) 6.6 Hz). 13C NMR (125.7
MHz, CDCl3): δ 170.1, 138.6, 138.5, 138.2, 137.2, 135.8, 128.5,
128.4, 128.4, 128.3, 128.1, 128.1, 128.0, 127.9, 127.9, 127.6,
127.6, 127.4, 117.3, 99.7, 96.3, 75.9, 74.6, 73.4, 72.9, 72.5, 71.8,
69.6, 68.6, 65.1, 62.7, 53.4, 51.9, 45.1, 39.4, 36.9, 35.2, 29.7,
29.1, 23.0, 22.7, 19.1, 15.5, 14.1. HRMS (FAB): M + H calcd
894.4792, found 894.4789. [R]D ) +18.0° (c 0.005, CHCl3).
Com p ou n d s 14 a n d 15. 29 (5.2 mg, 6.2 µmol) was
dissolved in 750 µL of CH2Cl2 and treated with MCPBA (3 mg,
18.5 µmol) for 12 h at which time another 3 mg of MCPBA
was added due to incomplete formation of product. After 12
h CSA (1.5 mg, 6.2 mmol) was added directly to the reaction
mixture and allowed to stir for an additional 24 h. The
reaction was quenched with 10 mL of saturated NaHCO3 and
extracted with EtOAc (4 × 25 mL). The C-glycosides were
chromatographed by preparatory TLC (10% MeOH/CH2Cl2) to
yield the benzylated precursors to compounds 14 and 15, 4.3
mg (80%). IR (neat): υmax 3357, 2924, 1719, 1655, 1455, 1377,
The bis-TBS ether (19 mg, 0.0169) was dissolved in 300 µL
of t-BuOH and 300 µL of H2O prior to adding K3Fe(CN)6 (50
mg), K2CO3 (25 mg), and the chiral ligand (DHQD)2‚pyr (2 mg).
This was stirred until a homogeneous mixture was obtained
and then cooled to 0 °C. At this point, potassium osmate (0.5
mg) was added and the reaction stirred for 4 h. This was
quenched with 3 mL of a saturated solution of sodium sulfite
and extracted with CH2Cl2 (4 × 25 mL). Chromatography
(TLC in 2/1 Hex/EtOAc) gave a minor (2.5 mg, eluted first)
and a major compound 30 (12.5 mg, eluted second) in a 1:5
ratio; total yield 77%. IR (neat): 3387, 2928, 1680, 1522, 1456,
1381, 1258, 1209, 1048 cm-1 1H NMR (500 MHz, CDCl3): δ
.
7.29 (m, 20H), 4.96 (d, 1H, J ) 11.6 Hz), 4.77 (d, 1H, J ) 11.6
Hz), 4.71 (m, 5H), 4.59 (d, 1H, J ) 11.6 Hz), 4.52 (d, 1H, J )
11.7 Hz), 4.39 (d, 1H, J ) 11.6 Hz), 4.29 (d, 1H, J ) 8.7 Hz),
4.24 (dd, 1H, J ) 5.5, 11.3 Hz), 4.18 (b, 1H), 4.11 (m, 2H),
3.80 (m, 3H), 3.68 (m, 2H), 3.60 (d, 1H, J ) 6.0 Hz), 3.57 (dd,
1H, J ) 3.2, 11.0 Hz), 3.49 (b, 1H), 3.35 (dd, 1H, J ) 7.9, 10.9
Hz), 3.33 (m, 1H), 1.98 (m, 4H), 1.91 (s, 3H), 1.49 (s, 3H), 1.45
(s, 3H), 1.42 (m, 1H), 1.30 (m, 1H), 0.96 (d, 1H, J ) 6.21 Hz),
0.82 (s, 9H), 0.81 (s, 9H), 0.15 (s, 3H), 0.06 (s, 3H), 0.02 (s,
3H), -0.02 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 170.1,
139.1, 138.5, 138.3, 136.9, 128.7, 128.4, 128.3, 128.2, 128.1,
128.0, 127.6, 127.6, 127.4, 99.9, 96.0, 79.8, 77.9, 75.9, 74.6, 74.3,
72.8, 70.6, 69.5, 69.4, 67.7, 67.1, 64.9, 62.8, 54.0, 53.4, 37.8,
35.8, 34.9, 29.7, 29.4, 25.9, 25.8, 22.6, 19.0, 17.9, 17.8, 16.9.
HRMS (FAB): M + H calcd 1156.6577, found 1156.6577. [R]D
) -8.0° (c 0.012, CH2Cl2).
1262, 1094, 735, 698 cm-1
.
1H NMR (500 MHz, d6-acetone):
δ 7.34 (m, 40H), 4.90-4.45 (m, 18H), 4.20-3.43 (m, 30H), 2.12
(m, 4H), 1.89 (s, 3H), 1.87 (s, 3H), 1.77-1.36 (m, 12H), 1.27
(d, 3H, J ) 6.4 Hz), 1.18 (d, 3H, J ) 6.4 Hz). HMQC with a
BIRD pulse (500 × 125 MHz, d6-acetone) indicates the follow-
ing 13C resonances: δ 137.3, 105.1, 104.9, 88.0, 86.5, 85.8, 85.7,
85.6, 85.2, 83.9, 82.7, 82.8, 81.5, 81.5, 81.5, 79.8, 79.7, 79.6,
79.3, 77.0, 76.9, 76.1, 74.6, 74.3, 74.1, 71.8, 71.8, 60.5, 59.6,
53.3, 50.3, 48.1, 44.6, 41.9, 41.8, 41.7, 38.3, 38.2, 33.3, 33.2,
31.8, 31.5, 30.4, 30.3, 25.0, 24.1. HRMS (FAB): M + H calcd
870.4428, found 870.4415.
Com p ou n d s 14 a n d 15. The tetrabenzylated precursors
(2 mg) were dissolved in 1 mL of dry MeOH. This was stirred
with 3.0 mg of Pd(OH)2 on carbon under a H2 atmosphere for
2 h. The solvent was filtered through a bed of Celite, isolating
the carbon bound Pd(OH)2. The MeOH was evaporated, and
the oil was chromatographed on silica gel (linear gradient
0-20% MeOH/CH2Cl2) to yield three main fractions. Fraction
1 contains a 9:1 mixture of trisaccharide diastereomers (0.9
mg), fraction 2 an approximate equal molar mixture (0.5 mg),
and fraction 3 a 1:7 mixture of diastereomers (0.5 mg).
F r a ction 1, com p ou n d 14. 1H NMR (500 MHz, CD3OD): δ
7.34 (m, 5H), 4.78 (d, 1H, J ) 1.7 Hz), 4.76 (d, 1H, J ) 12.3
Hz), 4.51 (d, 1H, J ) 12.2 Hz), 4.11 (m, 2H), 3.98-3.86 (m,
Com p ou n d 31. The bis-TBS ether diol (12.5 mg, 0.0108
mmol) was dissolved in 400 µL of CH2Cl2 and cooled to 0 °C.
After addition of Et3N (4 µL, 0.040 mmol) a molar solution of
MsCl in CH2Cl2 was added in two portions until no starting
material remained by TLC (0.0108 mmol). The reaction was
transferred directly onto a preparatory TLC plate (eluent 2/1
Hex/EtOAc, 0.25 mm thick, 20 cm × 10 cm) to isolate 11.5 mg
of the primary mesylate after elution (86%). IR (neat): 3364,
2928, 1684, 1522, 1456, 1360, 1258, 1177, 1048 cm-1
.
1H NMR
(400 MHz, CDCl3): δ 7.31 (m, 20H), 6.22 (b, 1H), 4.97 (d, 1H,

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5279
J ) 11.7 Hz), 4.79 (d, 1H, J ) 11.3 Hz), 4.68 (m, 5H), 4.59 (d,
1H, J ) 11.6 Hz), 4.53 (d, 1H, J ) 11.7 Hz), 4.39 (d, 1H, J )
11.6 Hz), 4.30 (d, 1H, J ) 8.9 Hz), 4.26-4.08 (m, 5H), 4.00 (m,
2H), 3.80 (m, 2H), 3.68 (m, 2H), 3.59 (d, 1H, J ) 6.0 Hz), 3.48
(b, 1H), 3.32 (dd, 1H, J ) 9.0, 9.0 Hz), 3.03 (s, 3H), 2.27-1.94
(m, 5H), 1.91 (s, 3H), 1.68 (m, 2H), 1.49 (s, 3H), 1.43 (s, 3H),
0.95 (d, 3H, J ) 5.8 Hz), 0.83 (s, 9H), 0.82 (s, 9H), 0.14 (s,
3H), 0.07 (s, 3H), 0.03 (s, 3H), -0.02 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 170.1, 139.1, 138.4, 138.3, 136.9, 128.7, 128.4,
128.3, 128.2, 128.1, 128.0, 127.6, 127.4, 127.3, 99.9, 96.0, 79.9,
77.9, 77.2, 75.8, 74.6, 74.4, 72.8, 70.5, 69.5, 67.2, 66.9, 64.9,
62.8, 37.4, 37.3, 35.8, 34.9, 29.7, 29.4, 25.9, 5.8, 22.6, 19.1, 17.9,
17.8, 16.9, 14.1, -3.8, -4.0, -4.5, -4.8. HRMS (FAB): M +
H calcd 1234.6352, found 1234.6375. [R]D ) -5.2° (c 0.012,
CH2Cl2).
3.9, 13.0 Hz), 3.76 (m, 1H), 3.72 (m, 5H), 3.61 (dd, 1H, J )
2.6, 11.6 Hz), 3.55 (dd, 1H, J ) 9.8, 9.8 Hz), 3.46 (dd, 1H, J )
7.8, 11.8 Hz), 2.03 (m, 1H), 1.77 (s, 3H), 1.68 (m, 4H), 1.44 (m,
4H), 1.28 (d, 3H, J ) 6.6 Hz). 13C NMR (125 MHz, CDCl3): δ
170.0, 138.5, 138.3, 138.0, 137.3, 128.5, 128.4, 128.3, 128.3,
128.2, 128.1, 128.1, 128.0, 127.9, 127.7, 127.4, 96.0, 73.9, 73.3,
73.1, 72.8, 72.7, 72.3, 69.7, 69.4, 68.9, 66.0, 64.5, 62.7, 50.5,
43.7, 39.1, 34.3, 31.3, 29.7, 23.0, 14.1.
Com p ou n d 14. Compound 33 (4.2 mg, 0.0048 mmol) was
dissolved in 2 mL of dry MeOH. This was stirred with 8 mg
of Pd(OH)2 on carbon under a H2 atmosphere until all starting
material was consumed. The solvent was filtered through a
bed of Celite, isolating the carbon bound Pd(OH)2. The MeOH
was evaporated, and the oil was chromatographed on silica
gel (linear gradient 0-20% MeOH/CH2Cl2) to yield compound
14 as a pure diastereomer, 2.2 mg (76% yield). 1H NMR (500
MHz, CD3OD): δ 7.38 (d, 2H, J ) 7.0 Hz), 7.33 (dd, 2H, J )
7.2, 7.7 Hz), 7.26 (d, 1H, J ) 12.0 Hz), 4.78 (d, 1H, J ) 3.2
Hz), 4.76 (d, 1H, J ) 12.0 Hz), 4.51 (d, 1H, J ) 12.0 Hz), 4.11
(m, 1H), 4.00-3.63 (m, 10H), 3.56 (m, 1H), 3.43 (m, 2H), 2.15
(m, 1H), 1.95 (s, 3H), 1.79 (dd, 1H, J ) 5.5, 13.7 Hz), 1.73 (m,
1H), 1.67 (m, 1H), 1.61-1.47 (m, 4H), 1.22 (d, 3H, J ) 6.5 Hz).
HMQC with a BIRD pulse (500 × 125 MHz, CD3OD) indicates
the following 13C resonances: δ 129.0, 128.7, 128.4, 96.2, 75.9,
75.7, 74.4, 73.1, 71.8, 70.9, 69.4, 69.3, 66.8, 66.0, 66.0, 62.6,
62.6, 52.8, 44.9, 39.0, 36.3, 33.4, 30.4, 22.6, 22.5, 22.3, 15.9.
HRMS (FAB): M + H calcd 600.3020, found 600.3018. [R]D
) +43° (c 0.0019, MeOH).
The primary mesylate (11.4 mg, 0.0092 mmol) was dissolved
in 0.5 mL of THF, treated with deoiled NaH (2.5 mg, 0.104
mmol), and stirred for 0.5 h. TLC showed incomplete forma-
tion of product, and an additional amount of NaH was
admitted to the reaction (1 mg, 0.042 mmol). After 0.5 h the
reaction was quenched with 1.5 mL of saturated NH4Cl and
then with 1.5 mL of brine. The reaction was extracted with
CH2Cl2 (3 × 25 mL) and submitted to silica gel chromatogra-
phy (TLC in 2/1 Hex/EtOAc) to yield 9.0 mg of the epoxide 31
(86%). IR (neat): 3355, 2928, 1682, 1512, 1456, 1372, 1258,
1047 cm-1 1H NMR (500 MHz, CDCl3): δ 7.28 (m, 20H), 6.29
.
(b, 1H), 4.96 (d, 1H, J ) 11.6 Hz), 4.77 (d, 1H, J ) 11.5 Hz),
4.74 (d, 1H, J ) 11.9 Hz), 4.69 (m, 3H), 4.59 (d, 1H, J ) 11.6
Hz), 4.52 (d, 1H, J ) 11.7 Hz), 4.38 (d, 1H, J ) 11.7 Hz), 4.26
(m, 1H), 4.21 (dd, 1H, J ) 5.6, 11.4 Hz), 4.13 (m, 3H), 3.80 (m,
2H), 3.69 (m, 2H), 3.61 (m, 1H), 3.48 (b, 1H), 3.32 (dd, 1H, J
) 9.1, 9.1 Hz), 2.92 (m, 1H), 2.74 (dd, 1H, J ) 4.0, 5.1 Hz),
2.41 (d, 1H, J ) 2.7, 5.2 Hz), 2.20 (b, 1H), 2.00 (m, 3H), 1.90
(s, 3H), 1.70 (m, 4H), 1.50 (s, 3H), 1.47 (s, 3H), 0.95 (d, 3H, J
) 4 Hz), 0.83 (s, 9H), 0.79 (s, 9H), 0.11 (s, 3H), 0.08 (s, 3H),
0.01 (s, 3H), -0.04 (s, 3H). 13C NMR (125 MHz, CDCl3): δ
170.1, 139.1, 138.5, 138.4, 137.0, 128.7, 128.4, 128.3, 128.2,
128.1, 128.0, 127.9, 127.6, 127.6, 127.5, 127.3, 99.9, 96.0, 79.8,
77.9, 75.9, 74.6, 74.2, 72.7, 70.6, 69.4, 67.2, 64.9, 62.8, 50.6,
48.1, 37.7, 35.8, 35.0, 29.7, 29.4, 25.9, 25.8, 22.7, 22.6, 19.0,
17.9, 17.9, 16.9, 14.1, -3.8, -3.9, -4.7, -4.7. HRMS (FAB):
M + H calcd 1138.6471, found 1138.6469. [R]D ) -8.9° (c
0.090, CH2Cl2).
Com p ou n d 34. The TBS ether 23 (2.0 g, 2.1 mmol) was
dissolved in 40 mL of THF and cooled to 0 °C. A 0.5 M solution
of 9-BBN in hexanes (8.0 mmol) was added dropwise, and the
solution was allowed to stir for 0.5 h at 0 °C and then for 0.5
h at room temperature. The reaction was recooled to 0 °C and
quenched with successive addition of 8 mL of EtOH, 16 mL of
a pH 7 phosphate buffer, 3 mL of 3 N NaOH, and 3 mL of
30% H2O2. The reaction stirred for 15 min at 0 °C, warmed
to room temperature, and stirred for 0.5 h at which time the
flask was diluted with 50 mL of brine, 50 mL of saturated NH4-
Cl, and 100 mL of EtOAc and stirred for 40 min. The reaction
was extracted with EtOAc (3 × 100 mL). The product was
purified by flash silica gel chromatography (TLC in 2/1 Hex/
EtOAc) to give a yellow oil, 1.2 g (60%). IR (neat): 3308, 2930,
1662, 1653, 1539, 1455, 1373, 1253, 1205, 1070, 837, 735, 698
Com p ou n d 32. The TBS-protected epoxide 31 (8.9 mg,
0.0078 mmol) was dissolved in 400 µL of THF and treated with
a 1.0 M solution of TBAF in THF (0.027 mmol). After 1 h the
reaction was quenched with 4 mL of brine and extracted with
CH2Cl2 (4 × 25 mL). Chromatography using preparatory TLC
(eluent 1/2 hex/EtOAc, 0.25 mm thick, 20 cm × 10 cm) yielded
5 mg of the epoxide diol 32 (70%). IR (neat): 3416, 2924, 1655,
cm-1 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 20H), 5.87 (d,
.
1H, J ) 9.8 Hz), 4.78 (d, 1H, J ) 11.8 Hz), 4.72 (m, 4H), 4.68
(d, 1H, J ) 11.8 Hz), 4.62 (d, 1H, J ) 11.9 Hz), 4.61 (d, 1H, J
) 11.8 Hz), 4.57 (d, 1H, J ) 11.7 Hz), 4.45 (d, 1H, J ) 11.8
Hz), 4.27 (dt, 1H, J ) 3.6, 11.7 Hz), 4.00 (m, 2H), 3.90 (m,
1H), 3.85-3.58 (m, 9H), 3.43 (t, 1H, J ) 9.6 Hz), 1.93 (m, 1H),
1.94 (s, 3H), 1.83 (m, 1H), 1.74-1.44 (m, 4H), 1.50 (s, 3H), 1.33
(s, 3H), 1.20 (d, 3H, J ) 6.6 Hz), 0.86 (s, 9H), 0.07 (s, 3H),
0.03 (s, 3H). 13C NMR (100.6 MHz, CDCl3): δ 170.3, 138.6,
138.5, 138.4, 137.0, 128.5, 128.3, 128.2, 128.2, 128.2, 128.1,
128.1, 127.8, 127.6, 127.6, 127.5, 127.5, 99.2, 96.2, 77.4, 76.7,
75.6, 73.4, 72.9, 69.6, 68.1, 65.1, 62.5, 59.7, 51.4, 37.2, 36.2,
36.1, 35.7, 31.0, 29.2, 25.8, 23.1, 19.0, 17.8, 15.6, -4.1, -4.9.
HRMS (FAB): M + H calcd 968.5344, found 968.5359. [R]D
) +13.8° (c 0.0474, CHCl3).
1541, 1454, 1375, 1070 cm-1 1H NMR (500 MHz, CDCl3): δ
.
7.30 (m, 20H), 6.07 (d, 1H, J ) 9.2 Hz), 4.81 (d, 1H, J ) 3.5
Hz), 7.74 (d, 1H, J ) 11.8 Hz), 4.73 (d, 1H, J ) 11.9 Hz), 4.70-
4.60 (m, 5H), 4.56 (d, 1H, J ) 11.7 Hz), 4.06 (m, 1H), 3.97 (m,
4H), 3.80-3.65 (m, 10H), 3.45 (dd, 1H, J ) 9.1, 9.1 Hz), 3.14
(m, 1H), 2.79 (dd, 1H, J ) 4.7, 4.7 Hz), 2.53 (dd, 1H, J ) 2.8,
4.8 Hz), 2.05 (m, 2H), 1.83 (s, 3H), 1.68 (m, 2H), 1.61 (m, 1H),
1.52 (m, 2H), 1.43 (s, 3H), 1.35 (s, 3H), 1.26 (b, 3H). 13C NMR
(125 MHz, CDCl3): δ 170.2, 138.6, 138.4, 138.1, 137.2, 128.5,
28.4, 128.4, 128.3, 128.1, 128.0, 127.9, 127.6, 127.6, 127.5, 99.7,
96.3, 75.7, 74.5, 73.3, 73.2, 73.0, 71.6, 70.3, 69.6, 68.8, 65.0,
62.7, 51.8, 50.7, 47.3, 46.4, 37.2, 36.9, 34.8, 29.7, 29.1, 23.0,
19.1. HRMS (FAB): M + H calcd 910.4742, found 910.4753.
[R]D ) +18° (c 0.005, CH2Cl2).
To a solution of alcohol (1.08 g, 1.24 mmol) in 20 mL of CH2-
Cl2 was added a freshly prepared solution of Dess-Martin
periodinane (DMP, 710 mg, 1.67 mmol) in 20 mL of CH2Cl2.
This solution was prepared by stirring the DMP with 20 mL
of CH2Cl2 for 20 min. The reaction was opened to the
atmosphere for 30 min, and then 10 mL of undistilled CH2Cl2
was added. After an additional 1 h of stirring the reaction
was quenched with 25 mL of 1.5 M sodium thiosulfate and 25
mL of saturated NaHCO3. After the aqueous layer was
extracted with CH2Cl2 (3 × 100 mL), the product was purified
on silica gel (TLC in 2/1 Hex/EtOAc) to give 34 1.05 g (97%).
IR (neat): 3272, 2929, 1717, 1652, 1539, 1516, 1455, 1373,
Com p ou n d 33. The epoxide diol (4.9 mg, 0.0054 mmol)
was dissolved in 400 µL of CH2Cl2 and treated with a catalytic
amount of CSA (<1 mg). After the solution was stirred for 5
h the reaction was transferred directly onto a preparatory TLC
plate (0.25 mm thick, 20 cm × 10 cm) to isolate 4.2 mg of 33
after elution (5% MeOH in CH2Cl2, 90% yield). 1H NMR (400
MHz, CDCl3): δ 7.27 (m, 20H), 5.81 (d, 1H, J ) 9.6 Hz), 4.78
(d, 1H, J ) 3.5 Hz), 4.76 (d, 1H, J ) 11.8 Hz), 4.70 (d, 1H, J
) 11.8 Hz), 4.68 (d, 1H, J ) 11.8 Hz), 4.59 (d, 1H, J ) 11.9
Hz), 4.57 (d, 1H, J ) 11.8 Hz), 4.55 (d, 1H, J ) 11.8 Hz), 4.48
(d, 1H, J ) 12.1 Hz), 4.45 (d, 1H, J ) 11.9 Hz), 4.11 (m, 1H),
4.03 (dd, 1H, J ) 3.2, 6.2 Hz), 3.96 (m, 3H), 3.82 (dd, 1H, J )
1308, 1265, 1204, 1074, 837, 734, 698 cm-1
.
1H NMR (500
MHz, CDCl3): δ 9.62 (d, 1H, J ) 3.7 Hz), 7.33 (m, 20H), 5.86
(d, 1H, J ) 9 Hz), 4.76-4.45 (m, 7H), 4.59 (d, 1H, J ) 11.6
Hz), 4.54 (d, 1H, J ) 11.6 Hz), 4.48 (d, 1H, J ) 12.0 Hz), 4.13
(m, 1H), 3.95 (m, 2H), 3.85 (br, 1H), 3.75 (m, 3H), 3.66 (m,
2H), 3.41 (dd, 1H, J ) 9.6, 9.6 Hz), 2.56 (m, 1H), 2.16 (ddd,

5280 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
1H, J ) 3.1, 11.7, 14.2 Hz), 1.94 (s, 3H), 1.80 (q, 1H, J ) 10.5
Hz), 1.73 (m, 1H), 1.68 (m, 1H), 1.49 (s, 3H), 1.46 (m, 1H),
1.36 (s, 3H), 1.23 (d, 3H, J ) 6.6 Hz), 0.87 (s, 9H), 0.05 (s,
3H), 0.03 (s, 3H). 13C NMR (125.7 MHz, CDCl3): δ 206.6,
170.5, 138.6, 138.5, 138.1, 137.2, 128.5, 128.3, 128.2, 128.0,
127.9, 127.8, 127.7, 127.6, 127.5, 99.2, 96.1, 75.9, 74.0, 73.0,
72.9, 69.4, 68.5, 65.0, 62.5, 53.4, 51.5, 50.6, 36.8, 36.1, 29.2,
25.8, 23.0, 19.0, 17.9, -4.1, -4.9. HRMS (FAB): M + H calcd
966.5188, found 966.5187. [R]D ) +28.5° (c 0.0332, CHCl3).
Com p ou n d 35. To a stirred solution of aldehyde 35 (40
mg, 0.0415 mmol) in 2 mL of THF, cooled to 0 °C, was added
a 1.0 M solution of allylmagnesium bromide (0.125 mmol,
Aldrich). After 30 min of continued stirring the reaction was
quenched with saturated NH4Cl and extracted with CH2Cl2.
The crude reaction mixture, showing only one spot by TLC
(2/1 Hex/EtOAc), was dissolved in 2 mL of THF and treated
with 1 M TBAF (0.0415 mmol) at 0 °C. After 2 h the reaction
was quenched with 2 mL of a saturated solution of NH4Cl and
2 mL of H2O and extracted with EtOAc. Silica gel chroma-
tography isolated the major compound 35, 18.2 mg (50%). IR
(neat): 3416, 2924, 1659, 1537, 1497, 1454, 1373, 1206, 1119,
(FAB): M + H calcd 870.4428, found 870.4429. [R]D ) +0.030°
(c 0.0024, CHCl3).
Com p ou n d 8. The tetrabenzylated precursor (2.5 mg, 2.87
µmol) was dissolved in 1 mL of dry MeOH. This was stirred
with 3.6 mg of Pd(OH)2 on carbon under a H2 atmosphere for
3 h. The solvent was filtered through a bed of Celite, isolating
the carbon bound Pd(OH)2. The MeOH was evaporated, and
the oil was chromatographed on silica gel (linear gradient
0-20% MeOH/CH2Cl2) to yield polyol 8. 1H NMR (500 MHz,
CD3OD): δ 7.32 (m, 5H), 4.75 (d, 1H, J ) 12.0 Hz), 4.68 (d,
1H, J ) 3.2 Hz), 4.52 (d, 1H, J ) 12.1 Hz), 4.16 (m, 1H), 4.03
(dd, 1H, J ) 3.4, 12.1 Hz), 3.89-3.82 (m, 3H), 3.70-3.58 (m,
6H), 3.50-3.42 (m, 3H), 3.33 (m, 1H), 2.11 (m, 1H), 1.97 (m,
2H), 1.94 (s, 3H), 1.81-1.69 (m, 3H), 1.59 (m, 2H), 1.20 (d,
3H, J ) 6.5 Hz). HMQC with a BIRD pulse (500 × 125 MHz)
indicates the following 13C resonances: δ 127, 96.4, 78.8, 77.4,
74.7, 74.4, 73.3, 72.0, 69.5, 69.4, 69.4, 66.2, 63.0, 62.9, 53.6,
47.2, 39.9, 33.0, 30.4, 25.0, 22.3, 16.3. HRMS (FAB): M + H
calcd 600.3020, found 600.3021. [R]D ) +60° (c 0.011, MeOH).
Com p ou n d 7. The tetrabenzylated precursor (2-3 mg) was
dissolved in 1 mL of dry MeOH. This was stirred with 3.6 mg
of Pd(OH)2 on carbon under a H2 atmosphere for 3 h. The
solvent was filtered through a bed of Celite, isolating the
carbon bound Pd(OH)2. The MeOH was evaporated, and the
oil was chromatographed on silica gel (linear gradient 0-20%
MeOH/CH2Cl2) to yield polyol 7, 2.0 mg (>95%). 1H NMR (500
MHz, CD3OD): δ 7.31 (m, 5H), 4.75 (d, 1H, J ) 12.1 Hz), 4.69
(d, 1H, J ) 3.4 Hz), 4.51 (d, 1H, J ) 12.1 Hz), 4.05 (m, 2H),
3.89-3.81 (m, 5H), 3.75-3.61 (m, 7H), 3.51 (dd, 1H, J ) 4.3,
11.6 Hz), 2.07 (m, 1H), 1.96 (m, 1H), 1.94 (s, 3H), 1.82-1.73
(m, 3H), 1.66 (m, 1H), 1.56 (m, 1H), 1.47 (m, 1H), 1.20 (d, 3H,
J ) 6.4 Hz). HMQC with a BIRD pulse (500 × 125 MHz, CD3-
OD) indicates the following 13C resonances: δ 124, 96.1, 74.3,
74.3, 74.1, 72.2, 71.4, 70.9, 70.3, 69.6, 68.7, 63.4, 63.0, 62.8,
53.5, 44.9, 40.1, 34.9, 33.5, 30.4, 25.8, 22.5, 16.5. HRMS
(FAB): M + H calcd 600.3020, found 600.3026. [R]D ) +40°
(c 0.011, MeOH).
1072, 1028, 735, 698 cm-1
.
1H NMR (400 MHz, CDCl3):
contaminated with ethyl acetate δ 7.31 (m, 20H), 5.80 (m, 1H),
5.17 (d, 1H, J ) 9.8 Hz), 5.04 (m, 2H), 4.83-4.64 (m, 7H), 4.60
(d, 1H, J ) 11.8 Hz), 4.56 (d, 1H, J ) 11.8 Hz), 4.45 (d, 1H, J
) 11.8 Hz), 4.13-3.70 (m, 11H), 3.50 (dd, 1H, J ) 9.0, 9.0 Hz),
2.31 (m, 1H), 2.13 (m, 1H), 1.85 (m, 1H), 1.84 (s, 3H), 1.82 (m,
2H), 1.49 (s, 3H), 1.34 (s, 3H), 1.30 (m, 1H), 1.20 (d, 3H, J )
6.5 Hz). 13C NMR (100.6 MHz, CDCl3): δ 170.5, 138.9, 138.6,
138.5, 137.0, 135.8, 128.7, 128.4, 128.3, 128.3, 128.1, 127.9,
127.7, 127.6, 127.5, 127.4, 116.8, 100.0, 96.3, 77.4, 77.3, 76.5,
73.7, 73.3, 73.3, 73.1, 71.1, 69.6, 68.1, 65.2, 62.6, 51.5, 46.0,
40.8, 38.7, 34.6, 29.0, 23.2, 21.1, 19.2, 16.0, 14.2. HRMS
(FAB): M + H calcd 894.4792, found 894.4800. [R]D ) +20.9°
(c 0.0091, CHCl3).
Tetr a ben zyla ted C-Tr isa cch a r id e P r ecu r sor s of 7 a n d
8. 35 (82.0 mg, 0.092 mmol) was dissolved in 1 mL of CH2Cl2
and treated with MCPBA (45 mg, 0.261) for 4 h. Upon
completion of the epoxidation, catlytic CSA (1.0 mg) was added
directly to the reaction mixture and allowed to stir for an
additional 15 h. The C-glycosides were separated by prepara-
tory TLC (5% MeOH/CH2Cl2) to yield the benzylated precur-
sors to compound 8, 25.0 mg (top band), and precursor to 7,
24.0 mg (bottom band); total yield 61%. Tetr a ben zyl P r e-
cu r sor to 8. IR (neat): υmax 3359, 2923, 1717, 1653, 1455,
Com p ou n d 36. The homoallylic alcohol 27 (23 mg, 0.0257
mmol) was dissolved in 2 mL of MeOH and cooled to -78 °C.
After 20 s of bubbling ozone through the reaction, 9 mg of
NaBH4 (0.238 mmol) was added and the solution was stirred
for 15 min as the reaction mixture warmed to RT. The solvent
was then evaporated without quench and was redissolved in
300 µL of CH2Cl2 and 2 drops of MeOH and placed directly
onto a preparatory TLC plate (25 mm thick, 20 cm × 20 cm)
and eluted with hexanes/EtOAc, 1/2; 16.4 mg of the diol was
isolated (71% yield). This diol (0.0160 mmol) was dried and
dissolved in 400 µL of CH2Cl2. After 7 µL of Et3N (0.05 mmol)
was added, 1.3 µL of MsCl (0.016 mmol) was syringed in and
the reaction was allowed to stir for 0.5 h. This reaction mixure
was then transferred directly onto a preparatory TLC plate
and eluted with 1/1 Hex/EtOAc to result in the isolation of
13.5 mg of compound 36 (77% yield). IR (neat): υmax 3444,
1377, 1260, 1049, 735, 698 cm-1
.
1H NMR (500 MHz, d6-
acetone): δ 7.30 (m, 20H), 4.85 (d, 1H, J ) 11.5 Hz), 4.79 (s,
2H), 4.75 (d, 1H, J ) 12.1 Hz), 4.73 (d, 1H, J ) 11.5 Hz), 4.70
(d, 1H, J ) 3.4 Hz), 4.60 (d, 1H, J ) 11.5 Hz), 4.59 (d, 1H, J
) 11.6 Hz), 4.47 (d, 1H, J ) 12.1 Hz), 4.18 (m, 1H), 3.96 (m,
1H), 3.94 (m, 1H), 3.85 (m, 1H), 3.82 (m, 1H), 3.80 (m, 1H),
3.69-3.61 (m, 4H), 3.47-3.32 (m, 5H), 2.14 (dd, 1H, J ) 3.3,
14.5 Hz), 2.07 (m, 1H), 1.89 (m, 3H), 2.05 (s, 3H), 1.79 (dd,
1H, J ) 4.0, 11.7 Hz), 1.69 (ddd, 1H, J ) 2.6, 6.4, 14.9 Hz),
1.58 (m, 2H), 1.20 (d, 3H, J ) 6.4 Hz). HMQC with a BIRD
2928, 1663, 1497, 1455, 1356, 1175, 1069, 837, 735, 698 cm-1
.
1H NMR (500 MHz, CDCl3): δ 7.32 (m, 20H), 5.66 (d, 1H, J )
9.4 Hz), 4.76 (d, 1H, J ) 3.4 Hz), 4.72 (d, 1H, J ) 11.9 Hz),
4.70 (d, 1H, J ) 11.9 Hz), 4.68 (d, 1H, J ) 12.0 Hz), 4.60 (d,
1H, J ) 12.0 Hz), 4.59 (d, 1H, J ) 10.6 Hz), 4.56 (d, 1H, J )
11.4 Hz), 4.53 (d, 1H, J ) 11.7 Hz), 4.41 (d, 1H, J ) 11.7 Hz),
4.38 (m, 1H), 4.05 (m, 1H), 4.00 (m, 3H), 3.86 (m, 1H), 3.78
(m, 2H), 3.68 (m, 3H), 3.44 (dd, 1H, J ) 9.5, 9.5 Hz), 3.13 (b,
1H), 2.97 (s, 3H), 1.90 (m, 2H), 1.81 (s, 3H), 1.70 (m, 1H), 1.47
(s, 3H), 1.38 (s, 3H), 1.25 (m, 5H), 0.82 (s, 9H), 0.04 (s, 3H),
-0.02 (s, 3H). 13C NMR (125.7 MHz, CDCl3): δ 169.8, 138.5,
138.5, 138.0, 137.2, 128.5, 128.4, 128.4, 128.3, 128.2, 128.0,
127.8, 127.7, 127.6, 127.6, 127.5, 99.5, 96.3, 75.3, 74.9, 73.4,
73.0, 72.9, 71.6, 69.6, 69.5, 69.1, 68.2, 67.2, 65.3, 62.7, 52.4,
37.0, 36.0, 33.9, 33.7, 29.7, 29.2, 25.9, 24.0, 23.0, 19.1, 17.9,
15.1, 14.2, -4.1, -4.3. HRMS (FAB): M + H calcd 1090.5382,
found 1090.5376. [R]D ) +18.6° (c 0.013.4, CH2Cl2).
pulse (500 × 125 MHz, d6-acetone) indicates the following 13
C
resonances: δ 147.5, 115.7, 98.2, 97.6, 97.3, 96.7, 96.6, 93.8,
93.5, 92.1, 92.0, 91.4, 89.2, 88.3, 87.5, 85.1, 82.4, 71.5, 66.1,
59.9, 57.6, 51.1, 49.2, 45.0, 44.9, 42.0, 35.7. HRMS (FAB): M
+ H calcd 870.4428, found 870.4430. Tetr a ben zyl P r ecu r sor
to 7. IR (neat): υmax 3359, 2925, 1721, 1655, 1455, 1377, 1262,
1049, 735, 698 cm-1 1H NMR (500 MHz, d6-acetone): δ 7.33
.
(m, 20H), 4.85 (d, 1H, J ) 11.6 Hz), 4.79 (s, 2H), 4.75 (d, 1H,
J ) 12.2 Hz), 4.68 (d, 1H, J ) 3.3 Hz), 4.67 (d, 1H, J ) 11.6
Hz), 4.64 (d, 1H, J ) 11.8 Hz), 4.61 (d, 1H, J ) 11.6 Hz), 4.47
(d, 1H, J ) 12.1 Hz), 4.29 (m, 1H), 4.06 (m, 1H), 3.92 (m, 2H),
3.88 (dd, 1H, J ) 2.4, 8.5 Hz), 3.84 (d, 1H, J ) 2.0 Hz), 3.78
(m, 2H), 3.70-3.58 (m, 4H), 3.48 (dd, 1H, J ) 4.2, 11.5 Hz),
3.25 (dd, 1H, J ) 9.4, 9.4 Hz), 2.00 (m, 1H), 1.90 (m, 2H), 1.86
(s, 3H), 1.81 (m, 2H), 1.66 (ddd, 1H, J ) 2.0, 7.3, 13.7 Hz),
1.58 (ddd, 1H, J ) 5.2, 8.4, 13.4 Hz), 1.46 (m, 1H), 1.21 (d,
3H, J ) 6.3 Hz). HMQC with a BIRD pulse (500 × 125 MHz,
CD3OD) indicates the following 13C resonances: δ 136.8, 134.2,
132.0, 132.0, 99.4, 81.2, 80.9, 80.3, 79.7, 78.4, 77.1, 76.9, 76.5,
76.2, 74.0, 73.8, 73.8, 73.2, 73.0, 72.4, 71.3, 76.9, 76.8, 76.0,
65.7, 47.0, 44.0, 37.9, 35.7, 33.2, 32.4, 26.1, 19.3. HRMS
Com p ou n d 37. Mesylate 36 (13 mg, 0.012 mmol) was
dissolved in 0.6 mL of Et2O and treated with 24 µL of a 1.0 M
solution of TBAF in THF (0.024 mmol) and an additional 100
µL of THF. This reaction was allowed to stir for 2 h until, by
TLC, the product spot appeared just below the starting
material and above the TBS-deprotected uncyclized material.

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5281
Then 0.5 mL of CH2Cl2 was added and the reaction mixture
was placed directly on a preparatory TLC plate and eluted with
1/1 Hex/EtOAc to give 8.0 mg of compound 37 (76% yield). IR
(neat): υmax 3420, 2924, 1661, 1539, 1455, 1375, 1204, 1071,
) 10.9 Hz), 4.63 (d, 1H, J ) 11.6 Hz), 4.59 (d, 1H, J ) 11.4
Hz), 4.56 (d, 1H, J ) 10.8 Hz), 4.45 (d, 1H, J ) 12.0 Hz), 4.12
(m, 1H), 4.00 (b, 2H), 3.95 (dd, 1H, J ) 3.3, 8.2 Hz), 3.93 (m,
1H), 3.84-3.67 (m, 9H), 3.65 (dd, 1H, J ) 1.4, 8.8 Hz), 3.24
(dd, 1H, J ) 9.7, 9.7 Hz), 2.14 (m, 1H), 1.92 (s, 3H), 1.84 (m,
1H), 1.75 (m, 2H), 1.57 (m, 1H), 1.39 (m, 1H), 1.36 (s, 3H),
1.34 (s, 3H), 1.27 (d, 3H, J ) 6.6 Hz). 13C NMR (100.6 MHz,
CDCl3): δ 169.8, 138.7, 138.4, 138.1, 137.6, 128.4, 128.4, 128.3,
128.2, 128.0, 127.9, 127.9, 127.7, 127.6, 127.5, 99.5, 96.4, 77.2,
73.7, 73.1, 72.7, 72.1, 69.5, 68.6, 65.1, 65.0, 62.8, 61.7, 53.6,
42.0, 34.6, 33.8, 31.4, 29.7, 29.2, 23.4, 19.0, 15.3. HRMS
(FAB): (M - C7H7O)+ calcd 772.4061, found 772.4083. [R]D
) +1.6° (c 0.0061, CH2Cl2).
737, 698 cm-1 1H NMR (500 MHz, CDCl3): δ 7.33 (m, 20H),
.
6.16 (d, 1H, J ) 8.6 Hz), 4.87 (d, 1H, J ) 3.5 Hz), 4.75 (d, 1H,
J ) 12.2 Hz), 4.72 (d, 1H, J ) 13.3 Hz), 4.58 (d, 1H, J ) 12.1
Hz), 4.54 (s, 2H), 4.53 (d, 1H, J ) 13.6 Hz), 4.46 (d, 1H, J )
12.0 Hz), 4.41 (d, 1H, J ) 11.9 Hz), 4.21 (dt, 1H, J ) 6.4, 6.4
Hz), 4.00 (b, 2H), 3.87 (dd, 1H, J ) 3.1, 5.5 Hz), 3.84-3.59 (m,
10H), 3.4 (m, 2H), 3.27 (b, 1H), 2.11 (m, 1H), 1.9 (s, 3H), 1.74
(m, 6H), 1.41 (d, 3H, J ) 7.3 Hz), 1.36 (s, 3H), 1.31 (s, 3H). 13
C
NMR (125.7 MHz, CDCl3): δ 170.2, 138.5, 138.3, 137.7, 137.5,
128.5, 128.4, 128.4, 128.2, 128.1, 127.9, 127.9, 127.7, 127.7,
127.6, 127.6, 99.2, 96.5, 78.8, 75.3, 75.2, 74.2, 73.9, 73.3, 73.0,
71.7, 70.5, 69.6, 65.1, 63.7, 62.9, 62.5, 53.4, 52.4, 45.3, 35.8,
33.1, 33.0, 29.7, 23.3, 19.2, 13.3. HRMS (FAB): M + H calcd
880.4636, found 880.4635. [R]D ) +45° (c 0.0082, CH2Cl2).
Com p ou n d 16. Compound 37 (8.1 mg, 0.0092 mmol) was
Com p ou n d 11. Compound 38 (6.1 mg, 0.0069 mmol) was
dissolved in 0.5 mL of CH2Cl2 and 3 drops of MeOH.
A
catalytic amount of PTSA (<0.1 mg) was added to the flask
which was allowed to stir for 16 h. The reaction mixture was
then transferred directly onto a preparatory TLC plate (25 mm
thick, 20 cm × 10 cm) and eluted with 5% MeOH in CH2Cl2 to
isolate 4.1 mg of the triol (70% yield).
dissolved in 0.5 mL of CH2Cl2 and 3 drops of MeOH.
A
catalytic amount of CSA (<0.2 mg) was added to the flask
which was allowed to stir for 16 h. The reaction mixture was
then transferred directly onto a preparatory TLC plate (25 mm
thick, 20 cm × 10 cm) and eluted with 5% MeOH in CH2Cl2 to
isolate 5.6 mg of the triol (73% yield). IR (neat): υmax 3413,
The triol (4.0 mg, 0.0048 mmol) was dissolved in 700 µL of
dry MeOH. This was stirred with 11 mg of Pd(OH)2 on carbon
under a H2 atmosphere for 45 min and filtered through a bed
of Celite, isolating the carbon bound Pd(OH)2. The MeOH was
evaporated, and the oil was chromatographed on silica gel
(linear gradient 0-20% MeOH/CH2Cl2) to yield compound 11,
2.0 mg (74% yield). 1H NMR (500 MHz, CD3OD): δ 7.38 (d,
2H, J ) 7.2 Hz), 7.32 (dd, 2H, J ) 7.1, 7.1 Hz), 7.27 (t, 1H, J
) 7.2 Hz), 4.75 (d, 1H, J ) 11.9 Hz), 4.68 (d, 1H, J ) 3.4 Hz),
4.50 (d, 1H, J ) 11.9 Hz), 4.07 (m, 2H), 3.80 (m, 4H), 3.70 (m,
2H), 3.65 (m, 4H), 3.49 (dd, 1H, J ) 9.7, 9.7 Hz), 3.18 (dd, 1H,
J ) 9.7, 9.7 Hz), 1.94 (s, 3H), 1.82 (m, 2H), 1.65 (m, 2H), 1.56
(m, 2H), 1.38 (m, 2H), 1.17 (d, 3H, J ) 6.5 Hz). 13C NMR (125.7
MHz, CD3OD): δ 173.5, 139.1, 129.5, 129.4, 128.9, 96.6, 77.3,
74.9, 72.7, 72.2, 71.1, 69.9, 69.8, 68.8, 64.0, 63.0, 53.7, 42.5,
41.4, 35.0, 34.9, 30.8, 22.7, 16.7. HRMS (FAB): M + H calcd
570.2914, found 570.2908. [R]D ) +18° (c 0.002, MeOH).
Com p ou n d s 39 a n d 40. Diol 35 (31.6 mg, 0.0343 mmol)
was dissolved in 2.5 mL of THF and stirred with 30 mg of Hg-
(O2CCF3)2 (0.0686 mmol) for 20 min, 15 mL of brine was added,
and the reaction was allowed to stir for an additional 30 min.
The reaction mixture was then transferred to a separatory
funnel and extrated with CH2Cl2 (4 × 25 mL), dried, and
evaporated. The two diastereomers were separated on pre-
paratory TLC plates (1/2 Hex/EtOAc) to give two compounds,
a top band containing 18.3 mg of 40 (46% yield) and a bottom
band containing 21.0 mg of 39 (53% yield); total yield, 99%.
Com p ou n d 39. IR (neat): υmax 4313, 2930, 1659, 1539, 1455,
2925, 1725, 1659, 1539, 1455, 1377, 1053, 735, 698 cm-1 1H
.
NMR (500 MHz, CDCl3): δ 7.30 (m, 20H), 5.85 (d, 1H, J ) 9.6
Hz), 4.79 (d, 1H, J ) 3.6 Hz), 4.76 (d, 1H, J ) 11.7 Hz), 4.69
(d, 1H, J ) 11.7 Hz), 4.67 (d, 1H, J ) 11.8 Hz), 4.56 (d, 1H, J
) 11.7 Hz), 4.54 (d, 1H, J ) 11.7 Hz), 4.51 (s, 2H), 4.46 (d,
1H, J ) 11.8 Hz), 4.00 (b, 1H), 3.95 (m, 1H), 3.93 (m, 2H),
3.90-3.82 (m, 3H), 3.80-3.72 (m, 5H), 3.67 (m, 2H), 3.40 (dd,
1H, J ) 9.5, 9.5 Hz), 1.96 (m, 2H), 1.82 (s, 3H), 1.78 (ddd, 1H,
J ) 3.1, 5.4, 12.7 Hz), 1.71 (m, 3H), 1.60 (ddd, 1H, J ) 1.9,
7.6, 15.4 Hz), 1.46 (m, 3H), 1.28 (d, 3H, J ) 6.7 Hz). 13C NMR
(125.7 MHz, CDCl3): δ 170.0, 138.3, 138.2, 137.9, 137.1, 128.5,
128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.4,
95.8, 75.1, 74.1, 73.4, 72.7, 71.9, 71.3, 69.5, 69.0, 63.6, 63.5,
62.5, 50.7, 43.2, 38.7, 32.9, 32.9, 29.7, 23.1. HRMS (FAB): M
+ H calcd 840.4323, found 840.4326. [R]D ) +55° (c 0.0056,
CH2Cl2).
The triol (5.6 mg, 0.0067 mmol) was dissolved in 2 mL of
dry MeOH. This was stirred with 29 mg of Pd(OH)2 on carbon
under a H2 atmosphere for 12 h before 10 µL of AcOH was
added and the concentration of the MeOH was reduced to 700
µL. After the solution was stirred for another 6 h, the solvent
was filtered through a bed of Celite, isolating the carbon bound
Pd(OH)2. The MeOH was evaporated, and the oil was chro-
matographed on silica gel (linear gradient 0-20% MeOH/CH2-
Cl2) to yield compound 16, 3.0 mg (79% yield). 1H NMR (400
MHz, CD3OD/D2O, 1/1): δ 7.38 (m, 5H), 4.78 (d, 1H, J ) 3.5
Hz), 4.75 (d, 1H, J ) 12.2 Hz), 4.52 (d, 1H, J ) 12.2 Hz), 4.06
(b, 1H), 3.97 (m, 1H), 3.91 (m, 1H), 3.89 (dd, 1H, J ) 5.5, 9.4
Hz), 3.81-3.64 (m, 9H), 3.43 (dd, 1H, J ) 9.8, 9.8 Hz), 2.10
(m, 1H), 1.94 (s, 3H), 1.74 (m, 4H), 1.52 (m, 3H), 1.20 (d, 3H,
J ) 6.5 Hz). 13C NMR (100.6 MHz, CD3OD/D2O, 1/1): δ 173.9,
138.7, 129.5, 129.2, 129.0, 96.1, 76.1, 74.4, 72.3, 71.6, 71.1, 70.0,
69.7, 69.0, 66.9, 62.7, 62.3, 52.7, 44.4, 38.7, 34.1, 33.6, 22.8,
16.5. [R]D ) +70° (c 0.003, CD3OD).
1375, 1202, 1069, 735, 698 cm-1 1H NMR (360 MHz, CDCl3):
.
δ 7.33 (m, 20H), 5.78 (d, 1H, J ) 9.6 Hz), 4.78-4.69 (m, 5H),
4.65 (d, 1H, J ) 11.6 Hz), 4.58 (d, 1H, J ) 11.8 Hz), 4.50 (d,
1H, J ) 11.8 Hz), 4.43 (d, 1H, J ) 11.8 Hz), 4.25 (m, 1H), 4.10
(m, 1H), 3.97 (m, 1H), 3.90-3.60 (m, 9H), 3.43 (dd, 1H, J )
10.0, 10.0 Hz), 2.21 (m, 1H), 2.12 (dd, 1H, J ) 4.5, 11.8 Hz),
2.04 (s, 3H), 1.95 (m, 2H), 1.74 (m, 1H), 1.57 (m, 4H), 1.46 (s,
3H), 1.38 (s, 3H), 1.24 (d, 3H, J ) 7.0 Hz). 13C NMR (90.6
MHz, CDCl3): δ 170.0, 138.6, 138.5, 138.3, 137.1, 128.5, 128.4,
128.4, 128.3, 128.3, 128.0, 127.9, 127.7, 127.6, 127.6, 99.5, 96.3,
77.2, 76.4, 76.0, 73.3, 73.1, 69.6, 68.4, 67.9, 67.5, 65.0, 63.4,
62.8, 52.9, 40.1, 38.6, 37.0, 31.3, 29.4, 25.5, 23.2, 19.3, 15.5,
14.1. HRMS (FAB): M + H calcd 1130.4108, found 1130.4111.
[R]D ) +2.3° (c 0.021, CH2Cl2). Com p ou n d 40. IR (neat):
υmax 3413, 2928, 1655, 1522, 1455, 1375, 1200, 1075, 735, 698
Com p ou n d 38. The olefin (17 mg, 0.019 mmol) from
allylmagnesium bromide addition to aldehyde 35 was ozonized
following the conditions in the synthesis of 16 to give 11.2 mg
of the diol (0.011 mmol, 66% yield). This diol was then
mesylated as before with 4.6 µL of Et3N (0.033 mmol) and 0.88
µL of MsCl (0.011 mmol) to isolate 8.5 mg of the primary
mesylate (0.0078 mmol, 71% yield). This mesylate was then
dissolved in 0.5 mL of THF and treated with 50 µL of a TBAF
solution, 1 M in THF (0.050 mmol), and stirred for 12 h. The
THF was evaporated, and the oil was redissolved in CH2Cl2,
transferred to a preparatory TLC plate (25 mm thick, 20 cm
× 10 cm), and eluted to give 7.1 mg of the cyclized monoalcohol
38 analogous to compound 37 (96% yield). IR (neat): υmax
cm-1 1H NMR (500 MHz, CDCl3): δ 7.30 (m, 20H), 5.51 (d,
.
1H, J ) 10.0 Hz), 4.79 (d, 1H, J ) 11.8 Hz), 4.76 (d, 1H, J )
12.0 Hz), 4.76 (d, 1H, J ) 3.7 Hz), 4.72 (d, 1H, J ) 11.8 Hz),
4.71 (d, 1H, J ) 11.7 Hz), 4.65 (d, 1H, J ) 11.4 Hz), 4.59 (d,
1H, J ) 11.8 Hz), 4.55 (d, 1H, J ) 11.3 Hz), 4.50 (m, 1H), 4.43
(d, 1H, J ) 11.6 Hz), 4.24 (m, 1H), 3.90-3.70 (m, 10H), 3.51
(m, 2H), 3.27 (dd, 1H, J ) 9.4, 9.4 Hz), 2.36 (dd, 1H, J ) 4.7,
11.7 Hz), 2.05 (m, 2H), 1.97 (d, 1H, J ) 4.2, 11.9 Hz), 1.95 (s,
3H), 1.85 (m, 2H), 1.76 (m, 1H), 1.54 (m, 1H), 1.45 (m, 1H),
1.40 (s, 3H), 1.31 (s, 3H), 1.24 (d, 3H, J ) 6.6 Hz). 13C NMR
(90.6 MHz, CDCl3): δ 169.9, 138.5, 138.4, 137.9, 137.3, 128.5,
128.4, 128.4, 128.2, 128.2, 128.1, 128.0, 127.9, 127.9, 127.6,
127.5, 99.3, 96.5, 77.5, 76.2, 76.0, 73.9, 73.6, 73.0, 71.6, 70.7,
3418, 2925, 1655, 1455, 1377, 1200, 1067, 735, 698 cm-1 1H
.
NMR (400 MHz, CDCl3): δ 7.32 (m, 20H), 6.19 (d, 1H, J ) 8.2
Hz), 4.86 (d, 1H, J ) 3.5 Hz), 4.76 (d, 1H, J ) 11.9 Hz), 4.75
(d, 1H, J ) 12.0 Hz), 4.70 (d, 1H, J ) 11.6 Hz), 4.67 (d, 1H, J

5282 J . Org. Chem., Vol. 62, No. 16, 1997
Sutherlin and Armstrong
69.5, 68.5, 65.0, 62.8, 60.4, 51.3, 45.7, 45.3, 38.3, 37.0, 29.1,
27.8, 23.6, 18.7, 15.8, 14.1. HRMS (FAB): (M - Cl)+ calcd
1094.4350, found 1094.4347. [R]D ) +16° (c 0.018, CH2Cl2).
Com p ou n d 41. Organomercury compound 39 (15.0 mg,
0.0133 mmol) was dissolved in 0.5 mL of DMF and treated
with 16 mg of NaBH4 (0.423 mmol). After 45 min of stirring,
10 mL of brine was added and the reaction stirred for an
additional hour. The reaction mixture was transferred to a
separatory funnel and extracted with CH2Cl2 (3 × 25 mL). The
crude oil was redissolved in CH2Cl2 and 2 drops of MeOH,
combined with catalytic PTSA (2 grains), and stirred for 12 h.
This reaction mixture was then transferred directly onto a
preparatory TLC plate and eluted with 5% MeOH in CH2Cl2
to yield 9.0 mg of 41 (79% yield). IR (neat): υmax 3339, 2926,
4H), 3.70-3.55 (m, 6H), 3.24 (dd, 1H, J ) 9.7, 9.7 Hz), 3.24
(dd, 1H, J ) 9.3, 9.3 Hz), 2.00 (bd, 1H, J ) 17.1 Hz), 1.93 (s,
3H), 1.90 (ddd, 1H, J ) 1.8, 5.4, 15.3 Hz), 1.26 (m, 1H), 1.19
(d, 3H, J ) 6.5 Hz), 1.18 (d, 3H, J ) 6.2 Hz). 13C NMR (100.6
MHz, CD3OD): δ 173.3, 139.1, 129.4, 129.4, 128.9, 96.4, 80.3,
74.8, 74.6, 73.7, 73.0, 72.5, 72.1, 71.3, 70.1, 69.9, 69.3, 63.0,
53.4, 46.6, 44.1, 41.6, 35.2, 30.7, 25.3, 22.7, 21.6, 16.6. HRMS
(FAB): (M - C7H7O)+ calcd 476.2496, found 476.2492. [R]D
) +36° (c 0.0061, MeOH).
Com p ou n d 43. t-BuOK (36 mg, 0.032 mmol) was dissolved
in 1 mL of THF, and 82 µL of the MOM-protected allyl alcohol
(0.064 mmol) was syringed in and allowed to stir for 15 min
prior to cooling the flask to -78 °C. At this time, 120 µL of a
2.0 M solution of n-BuLi in pentane (0.024 mmol) was added
dropwise followed by continued stirring for 1.5 h. Then 152
1655, 1541, 1497, 1455, 1375, 1049, 735, 698 cm-1 1H NMR
.
(360 MHz, CDCl3): δ 7.32 (m, 20H), 5.63 (d, 1H, J ) 9.5 Hz),
4.79 (d, 1H, J ) 11.9 Hz), 4.78 (d, 1H, J ) 11.1 Hz), 4.71 (m,
3H), 4.65 (d, 1H, J ) 11.5 Hz), 4.59 (d, 1H, J ) 12.0 Hz), 4.56
(d, 1H, J ) 11.8 Hz), 4.45 (d, 1H, J ) 11.7 Hz), 4.24 (m, 2H),
3.94-3.76 (m, 10H), 3.68 (dq, 1H, J ) 4.7, 4.7 Hz), 3.35 (m,
2H), 2.00 (bd, 1H, J ) 15.3 Hz), 1.80 (dd, 1H, J ) 4.4, 14.6
Hz), 1.75 (s, 3H), 1.67 (m, 2H), 1.50 (dd, 1H, J ) 7.5, 15.2 Hz),
1.33 (m, 1H), 1.24 (d, 3H, J ) 6.9 Hz), 1.22 (d, 3H, J ) 6.6
Hz). 13C NMR (90.6 MHz, CDCl3): δ 170.2, 138.6, 138.2, 138.0,
137.0, 128.5, 128.3, 128.2, 128.1, 128.1, 128.0, 128.0, 127.8,
127.6, 127.5, 127.4, 95.6, 77.7, 77.1, 75.9, 74.2, 73.5, 73.0, 72.2,
71.7, 69.2, 68.5, 67.7, 67.5, 63.4, 51.1, 45.1, 43.6, 37.8, 34.8,
29.6, 27.7, 23.1, 18.3, 15.6. HRMS (FAB): M + H calcd
854.4479, found 854.4476. [R]D ) +5.6° (c 0.0090, CH2Cl2).
Com p ou n d 9. 41 (9.0 mg, 0.0105 mmol) was dissolved in
1 mL of dry MeOH. This was stirred with 20 mg of Pd(OH)2
on carbon under a H2 atmosphere for 1.5 h and filtered through
a bed of Celite, isolating the carbon bound Pd(OH)2. The
MeOH was evaporated, and the oil was chromatographed on
silica gel (linear gradient 0-20% MeOH/CH2Cl2) to yield
compound 9, 3.8 mg (62% yield). 1H NMR (400 MHz, CD3-
OD): δ 7.32 (m, 5H), 4.75 (d, 1H, J ) 12.0 Hz), 4.72 (d, 1H, J
) 3.5 Hz), 4.50 (d, 1H, J ) 12.0 Hz), 4.22 (m, 1H), 4.05 (m,
1H), 3.83 (m, 5H), 3.66 (m, 6H), 3.27 (dd, 1H, J ) 9.5, 9.5 Hz),
1.95 (m, 1H), 1.93 (s, 3H), 1.70 (m, 5H), 1.41 (m, 1H), 1.21 (m,
7H). 13C NMR (100.6 MHz, CD3OD): δ 173.1, 138.9, 129.3,
129.2, 128.7, 96.3, 74.8, 74.4, 72.4, 72.0, 71.1, 69.8, 69.0, 68.6,
67.2, 62.9, 53.3, 45.1, 41.6, 38.7, 35.1, 30.2, 26.1, 22.7, 19.4,
16.6. HRMS (FAB): M + H calcd 504.3071, found 504.3070.
[R]D ) +32° (c 0.0038, MeOH).
BOMe was added in 280 µL of THF. After 3 h
mg of (-)-Ipc2
of stirring, 69.0 µL of BF3OEt2 (0.056 mmol) was added
followed immediately by 154 mg of aldehyde 34 (0.016 mmol).
The reaction mixture stirred at -78 °C for 4 h and was then
allowed to warm to 10 °C slowly overnight, 12 h. The reaction
was quenched with 1 mL of 3 N NaOH and 1 mL of 30% H2O2
and stirred for 4 h to insure complete oxidation of the boron.
The contents of the flask were diluted with 15 mL of brine
and transferred to a separatory funnel and extracted with CH2-
Cl2 (4 × 30 mL). Column chromatography (2/1 Hex/EtOAc)
isolated 95 mg of the alcohol (57% yield). IR (neat): υmax 3428,
2928, 1682, 1499, 1455, 1774, 1262, 1071, 837, 735, 698 cm-1
.
1H NMR (400 MHz, CDCl3): δ 7.32 (m, 20H), 5.77 (ddd, 1H, J
) 6.1, 10.6, 16.9 Hz), 5.64 (d, 1H, J ) 10.0 Hz), 5.34 (dd, 1H,
J ) 0.8, 17.2 Hz), 5.01 (d, 1H, J ) 11.8 Hz), 4.89 (d, 1H, J )
11.7 Hz), 4.78-4.61 (m, 9H), 4.42 (d, 1H, J ) 11.7 Hz), 4.24
(m, 1H), 4.15 (dd, 1H, J ) 2.6, 10.7 Hz), 4.08 (m, 2H), 3.98
(ddd, 1H, J ) 3.5, 10.2, 11.4 Hz), 3.82 (d, 1H, J ) 9.1 Hz),
3.79 (dd, 1H, J ) 4.0, 9.3 Hz), 3.71 (dd, 1H, J ) 3.0, 9.0 Hz),
3.67 (m, 3H), 3.59 (m, 1H), 3.43 (dd, 1H, J ) 9.4, 9.4 Hz), 3.35
(s, 3H), 2.08 (m, 1H), 1.72 (m, 1H), 1.66 (m, 1H), 1.63 (ddd,
1H, J ) 4.8, 9.8, 14.4 Hz), 1.50 (s, 3H), 1.37 (m, 2H), 1.31 (s,
3H), 1.26 (s, 3H), 1.11 (d, 3H, J ) 6.4 Hz), 0.83 (s, 9H), 0.04
(s, 3H), 0.01 (s, 3H). 13C NMR (100.6 MHz, CDCl3): δ 170.2,
138.7, 138.7, 138.6, 137.2, 136.0, 128.5, 128.3, 128.3, 128.2,
128.2, 128.1, 127.8, 127.6, 127.5, 127.5, 127.5, 99.3, 96.5, 94.6,
78.2, 77.2, 76.1, 74.2, 72.9, 72.8, 71.1, 69.5, 67.4, 65.3, 62.6,
55.5, 51.4, 36.1, 35.1, 29.7, 29.3, 25.8, 23.1, 19.0, 17.8, 16.7,
-4.2, -4.7. HRMS (FAB): M + H calcd 1068.5868, found
1068.5875. [R]D ) -12° (c 0.017, CH2Cl2).
Com p ou n d 42. Organomercury compound 40 (18.2 mg,
0.0161 mmol) was treated under the same conditions reported
for compound 41, using 20 mg of NaBH4 (0.530 mmol) followed
by catalytic PTSA to give 10.6 mg of 42 (79% yield). IR
(neat): υmax 3341, 2925, 1655, 1542, 1497, 1455, 1375, 1059,
The alcohol (13 mg, 0.012 mmol) was dissolved in 1 mL of
CH2Cl2 and 100 µL of MeOH, and the solution was stirred for
4 h with catalytic PTSA (<0.2 mg). The solution was evapo-
rated and redissolved in CH2Cl2 for transfer onto a preparatory
TLC plate and eluted with 5% MeOH in CH2
Cl2 to yield 8.1
3326, 2925,
735, 698 cm-1
.
1H NMR (500 MHz, CDCl3): δ 7.31 (m, 20H),
mg of the tetrol 43 (72% yeild). IR (neat): υmax
5.23 (d, 1H, J ) 10.0 Hz), 4.81 (d, 1H, J ) 11.8 Hz), 4.79 (d,
1H, J ) 11.9 Hz), 4.75 (d, 1H, J ) 11.6 Hz), 4.72 (m, 1H), 4.72
(d, 1H, J ) 3.7 Hz), 4.65 (d, 1H, J ) 11.3 Hz), 4.59 (d, 1H, J
) 11.7 Hz), 4.58 (d, 1H, J ) 11.3 Hz), 4.45 (d, 1H, J ) 11.6
Hz), 4.30 (m, 1H), 4.00-3.75 (m, 7H), 3.68 (dq, 1H, J ) 4.6,
4.6 Hz), 3.67 (b, 1H), 3.50 (m, 2H), 3.28 (dd, 1H, J ) 9.7, 9.7
Hz), 2.97 (dd, 1H, J ) 9.9, 9.9 Hz), 2.11 (bd, 1H, J ) 15.5 Hz),
1.94 (ddd, 1H, J ) 1.2, 4.6, 11.2 Hz), 1.81 (ddd, 1H, J ) 3.6,
10.0, 14.6 Hz), 1.72 (s, 3H), 1.70 (m, 1H), 1.49 (m, 1H), 1.37
(dd, 1H, J ) 6.5, 9.9 Hz), 1.21 (m, 6H). 13C NMR (90.6 MHz,
CDCl3): δ 170.2, 138.6, 138.2, 138.0, 137.0, 128.5, 128.3, 128.2,
128.2, 128.1, 128.0, 128.0, 127.8, 127.6, 127.5, 127.4, 95.7, 80.6,
78.0, 77.5, 76.0, 73.6, 73.1, 72.4, 71.9, 69.3, 68.5, 63.4, 51.2,
44.5, 43.3, 42.2, 34.3, 29.6, 27.6, 23.1, 21.1, 15.7. HRMS
(FAB): (M - C7H7O)+ calcd 746.3904, found 746.3901. [R]D
) 0.0° (c 0.010, CH2Cl2).
1655, 1541, 1455, 1375, 1210, 1028, 735, 698 cm-1 1H NMR
.
(500 MHz, CDCl3): δ 7.33 (m, 20H), 5.62 (d, 1H, J ) 9.8 Hz),
5.52 (ddd, 1H, J ) 2.0, 8.3, 17.5 Hz), 5.23 (dd, 1H, J ) 1.1,
10.4 Hz), 5.16 (d, 1H, J ) 17.1 Hz), 4.80 (d, 1H, J ) 11.7 Hz),
4.76 (d, 1H, J ) 11.9 Hz), 4.75 (d, 1H, J ) 11.3 Hz), 4.73 (m,
2H), 4.70 (d, 1H, J ) 12.0 Hz), 4.69 (d, 1H, J ) 11.9 Hz), 4.68
(m, 1H), 4.59 (d, 1H, J ) 11.7 Hz), 4.56 (m, 2H), 4.45 (d, 1H,
J ) 11.8 Hz), 3.94 (m, 5H), 3.85 (dd, 1H, J ) 4.5, 11.2 Hz),
3.77 (m, 7H), 3.71 (dd, 1H, J ) 4.7, 9.3 Hz), 3.40 (dd, 1H, J )
9.4, 9.4 Hz), 3.36 (s, 3H), 1.97 (bd, 1H, J ) 15.0 Hz), 1.64 (b,
1H), 1.50 (ddd, 1H, J ) 9.2, 9.2, 15.3 Hz), 1.20 (d, 3H, J ) 6.5
Hz). 13C NMR (125.7 MHz, CDCl3): δ 170.1, 138.6, 138.5,
138.3, 137.3, 133.8, 128.6, 128.4, 128.3, 128.1, 128.1, 128.0,
128.0, 127.9, 127.7, 127.6, 127.6, 127.4, 127.1, 95.7, 94.1, 79.9,
78.1, 76.2, 74.9, 74.0, 73.7, 73.4, 73.0, 72.1, 71.9, 69.3, 68.5,
63.7, 55.8, 51.1, 43.9, 43.7, 37.1, 29.7, 23.2, 20.8, 15.8. HRMS
(FAB): M + H calcd 914.4691, found 914.4694. [R]D ) -2.5°
(c 0.0081, CH2Cl2).
Com p ou n d 44. Compound 43 (8.0 mg, 0.0088 mmol) was
dissolved in 800 µL of THF and stirred with 15 mg of Hg(O2-
CCF3)2 for 30 min before addition of 8 mL of brine and 45 min
of further stirring. The reaction was then transferred to a
separatory funnel and extracted with CH2Cl2 (3 × 25 mL). The
crude oil was checked for reaction completion by 1H NMR and
then redissolved in 800 µL of DMF. This solution was treated
Com p ou n d 10. 42 (10.6 mg, 0.0124 mmol) was dissolved
in 1 mL of dry MeOH. This was stirred with 20 mg of Pd-
(OH)2 on carbon under a H2 atmosphere for 1.5 h and filtered
through a bed of Celite, isolating the carbon bound Pd(OH)2.
The MeOH was evaporated, and the oil was chromatographed
on silica gel (linear gradient 0-20% MeOH/CH2Cl2) to yield
compound 10, 6.1 mg (84% yield). 1H NMR (400 MHz, CD3-
OD): δ 7.35 (m, 5H), 4.76 (d, 1H, J ) 12.0 Hz), 4.71 (d, 1H, J
) 3.5 Hz), 4.51 (d, 1H, J ) 12.0 Hz), 4.13 (m, 1H), 3.85 (m,

Stereochemically and Structurally Diverse C-Trisaccharides
J . Org. Chem., Vol. 62, No. 16, 1997 5283
with 8.0 mg of NaBH4 (0.22 mmol) and stirred for 30 min. At
this point, 4 mL of brine was added, the reaction was stirred
for 1.5 h, and the solution was extracted again with CH2Cl2
(3 × 25 mL). This crude oil was also checked for reaction
Com p ou n d 18. Compound 45 (25 mg, 0.024 mmol) was
dissolved in 1 mL of THF and stirred with 120 µL of a 1 M
TBAF solution in THF (0.120 mmol) for 24 h. The solution
was diluted with 5 mL of brine and extracted with CH2Cl2 (3
× 30 mL). The crude oil was chromatographed on preparatory
TLC (2/1 Hex/EtOAc) to yield 13 mg of the fully protected
oxetane (65% yield). IR (neat): υmax 3306, 2932, 1662, 1541,
1
completion by H NMR prior to dissolving the oil in 2 mL of
MeOH and 200 µL of CH2Cl2. One drop of concentrated HCl
was added and the reaction stirred overnight for 11 h and then
for 2 h after the addition of 2 more drops of acid. The MeOH
was evaporated and redissolved in CH2Cl2. This solution was
dried without extraction and placed on a preparatory TLC
plate (5% MeOH/CH2Cl2) to give 4.5 mg of 44 (60% overall
yield). IR (neat): υmax 3359, 2925, 1655, 1541, 1455, 1375,
1454, 1374, 1266, 1204, 1118, 856 cm-1 1H NMR (500 MHz,
.
CDCl3): δ 7.32 (m, 20H), 6.22 (d, 1H, J ) 8.4 Hz), 4.87 (d, 1H,
J ) 3.2 Hz), 4.72 (d, 1H, J ) 12.0 Hz), 4.71 (d, 1H, J ) 14.2
Hz), 4.68 (d, 1H, J ) 12.1 Hz), 4.65 (d, 1H, J ) 12.1 Hz), 4.60
(d, 1H, J ) 11.5 Hz), 4.58 (d, 1H, J ) 11.8 Hz), 4.50 (m, 2H),
4.43 (d, 1H, J ) 11.8 Hz), 4.23 (dd, 1H, J ) 6.6, 6.6 Hz), 3.93-
3.85 (m, 3H), 3.80-3.74 (m, 3H, 3.69-3.62 (m, 3H), 3.41 (m,
1H), 2.59 (m, 1H), 1.96 (m, 1H), 1.93 (s, 3H), 1.85 (m, 2H),
1.68 (m, 4H), 1.41 (s, 3H), 1.32 (s, 3H), 1.24 (d, 1H, J ) 6.6
Hz). HRMS (FAB): M + H calcd 836.4374, found 836.4369.
[R]D ) +50° (c 0.013, CHCl3).
1055, 735, 698 cm-1 1H NMR (500 MHz, CDCl3): δ 7.31 (m,
.
20H), 5.60 (d, 1H, J ) 9.7 Hz), 4.79 (d, 1H, J ) 12.0 Hz), 4.76
(d, 1H, J ) 4.6 Hz), 4.73 (d, 1H, J ) 10.3 Hz), 4.69 (m, 2H),
4.65 (d, 1H, J ) 11.5 Hz), 4.59 (d, 1H, J ) 12.2 Hz), 4.56 (d,
1H, J ) 12.0 Hz), 4.45 (d, 1H, J ) 11.7 Hz), 4.25 (m, 1H), 3.92
(m, 1H), 3.85 (m, 3H), 3.78 (m, 2H), 3.69 (m, 1H), 3.54 (m,
1H), 3.29 (dq, 1H, J ) 9.4, 9.4 Hz), 2.05 (bd, 1H, J ) 15.4 Hz),
1.82 (m, 1H), 1.71 (s, 3H), 1.65 (m, 2H), 1.51 (m, 1H), 1.43 (m,
1H), 1.29 (d, 3H, J ) 6.7 Hz), 1.29 (d, 3H, J ) 6.8 Hz). 13C
NMR (125.7 MHz, CDCl3): δ 170.3, 138.6, 138.3, 138.0, 137.1,
128.6, 128.4, 128.4, 128.3, 128.3, 128.2, 128.1, 128.0, 128.0,
127.7, 127.6, 127.5, 95.7, 77.7, 75.9, 73.8, 73.6, 73.3, 73.1, 72.4,
72.3, 71.8, 71.7, 69.4, 68.8, 63.4, 51.3, 44.1, 43.3, 34.5, 29.7,
27.5, 23.1, 22.7, 14.1, 12.0. HRMS (FAB): M + H calcd
870.4428, found 870.4407. [R]D ) -20° (c 0.0046, CH2Cl2).
Com p ou n d 17. Compound 44 (4.5 mg, 0.0052 mmol) and
8 mg of Pd(OH)2 on carbon were dissolved in 1 mL of MeOH.
The reaction was stirred under a hydrogen atmosphere for 2.5
h at which time the reaction was filtered through a bed of
Celite to filter out the carbon bound Pd. The solvent was
evaporated, and the oil was chromatographed on silica gel
(linear gradient 0-20% MeOH/CH2Cl2) to yield 1.9 mg of 17
(62% yield). 1H NMR (400 MHz, CD3OD): δ 7.33 (m, 5H), 4.75
(d, 1H, J ) 11.9 Hz), 4.71 (d, 1H, J ) 3.5 Hz), 4.52 (d, 1H, J
) 12.1 Hz), 4.15 (m, 1H), 4.09 (dd, 1H, J ) 6.1, 6.8 Hz), 3.85
(m, 4H), 3.64 (m, 5H), 3.47 (dd, 1H, J ) 5.7, 9.1 Hz), 1.96 (m,
1H), 1.94 (s, 3H), 1.82 (m, 1H), 1.70 (m, 1H), 1.42 (m, 3H),
1.22 (d, 3H, J ) 6.9 Hz), 1.20 (d, 3H, J ) 6.4 Hz). 13C NMR
(100.6 MHz, CDCl3): δ 173.4, 139.1, 129.4, 129.4, 128.9, 96.4,
74.7, 74.7, 74.3, 73.7, 73.4, 72.6, 72.1, 71.0, 70.1, 69.9, 69.3,
63.0, 53.4, 46.0, 41.4, 34.8, 22.7, 16.6, 12.6. [R]D ) +40° (c
0.0015, CH3OH).
The fully protected oxetane (13.0 mg, 0.0155) was dissolved
in MeOH and treated with catalytic PTSA (<0.2 mg). After
disappearance of starting material the MeOH was evaporated
and the reaction was redissolved in CH2Cl2. The reaction was
quenched with 10 mL of saturated sodium bicarbonate and
extracted with CH2Cl2 (3 × 25 mL) and chromatographed (TLC
in 5% MeOH/CH2Cl2) to give 11.2 mg of the tetrabenzylated
diol precursor to compound 18 (91% yield). IR (neat): υmax
3306, 2929, 1653, 1547, 1455, 1374, 1107, 1026, 735, 698 cm-1
.
1H NMR (400 MHz, CDCl3): δ 7.32 (m, 20H), 5.73 (d, 1H, J )
9.3 Hz), 4.87 (d, 1H, J ) 3.5 Hz), 4.75-4.48 (m, 8H), 4.13-
3.90 (m, 5H), 3.82-3.67 (m, 9H), 3.46 (m, 1H), 3.22 (dd, 1H, J
) 9.8, 9.8 Hz), 3.05 (b, 1H), 2.09 (m, 2H), 1.94 (s, 3H), 1.73
(m, 4H), 1.34 (d, 3H, J ) 6.7 Hz). 13C NMR (125.7 MHz,
CDCl3): δ 169.6, 138.6, 138.4, 138.1, 137.2, 128.6, 128.4, 128.4,
128.3, 128.2, 128.1, 128.1, 128.0, 127.8, 127.6, 127.6, 127.4.
HRMS (FAB): M + H calcd 796.4061, found 796.4078. [R]D
) +58° (c 0.0096, CHCl3).
The benzylated diol and 10 mg of Pd(OH)2 on carbon were
dissolved in 1.5 mL of MeOH. The reaction was stirred under
a hydrogen atmosphere for 4 h at which time the reaction was
filtered through a bed of Celite to filter out the carbon bound
Pd. The solvent was evaporated, and the oil was chromato-
graphed on silica gel (linear gradient 0-20% MeOH/CH2Cl2)
to yield 3.1 mg of 18 (38% yield). IR (neat): υmax 3368, 2926,
1653, 1559, 1455, 1375, 1024 cm-1 1H NMR (500 MHz, CD3-
.
Com p ou n d 45. The primary alcohol (32 mg, 0.033 mmol)
was dissolved in 0.5 mL of CH2Cl2 followed by the addition of
7.0 µL of Et3N (0.10 mmol). After the solution was stirred for
15 min, 6 µL of MsCl (0.078 mmol) was added and the reaction
stirred for an additional 0.5 h before being quenched with 4
mL of saturated sodium bicarbonate. The mixture was
extracted with CH2Cl2 (4 × 25 mL), and 25.6 mg of mesylate
45 was isolated from preparatory TLC (2/1 Hex/EtOAc, 74%
yield). IR (neat): υmax 3384, 2930, 1678, 1455, 1358, 1048, 699
OD): δ 7.32 (m, 5H), 4.85 (d, 1H, J ) 3.4 Hz), 4.78 (d, 1H, J
) 12.0 Hz), 4.53 (d, 1H, J ) 12.0 Hz), 4.16 (m, 1H), 4.09 (m,
1H), 3.90 (dd, 1H, J ) 3.4, 11.8 Hz), 3.87 (dd, 1H, J ) 5.4, 9.0
Hz), 3.77 (m, 2H), 3.68 (m, 1H), 3.65 (dd, 1H, J ) 3.5, 9.1 Hz),
3.63 (m, 2H), 3.61 (dd, 1H, J ) 5.7, 11.8 Hz), 3.53 (dd, 1H, J
) 5.6, 10.7 Hz), 3.21 (dd, 1H, J ) 9.9, 9.9 Hz), 2.22 (m, 1H),
2.15 (m, 1H), 1.91 (s, 3H), 1.83 (m, 2H), 1.76 (m, 1H), 1.21 (d,
3H, J ) 6.5 Hz). 13C NMR (125.7 MHz, CDCl3): δ 173.0, 139.2,
129.4, 129.3, 128.8, 96.7, 82.6, 78.5, 75.8, 75.4, 72.6, 72.1, 70.2,
70.1, 69.9, 68.9, 63.6, 63.3, 54.1, 44.7, 43.6, 34.1, 30.8, 24.8,
22.4, 16.6. HRMS (FAB): M + H calcd 526.2652, found
526.2653. [R]D ) +80° (c 0.003, CH2Cl2).
cm-1 1H NMR (500 MHz, CDCl3): δ 7.29 (m, 20H), 5.83 (d,
.
1H, J ) 9.7 Hz), 4.82 (d, 1H, J ) 11.7 Hz), 4.74 (d, 1H, J )
11.8 Hz), 4.71 (d, 1H, J ) 3.5 Hz), 4.70-4.66 (m, 3H), 4.59 (d,
1H, J ) 11.6 Hz), 4.57 (d, 1H, J ) 11.7 Hz), 4.41 (d, 1H, J )
11.8 Hz), 4.25 (dd, 1H, J ) 6.2, 9.8 Hz), 4.19 (dd, 1H, J ) 7.5,
9.9 Hz), 4.70 (m, 2H), 4.00 (m, 1H), 3.92 (ddd, 1H, J ) 3.6,
9.9, 11.7 Hz), 3.37 (dd, 1H, J ) 9.7, 9.7 Hz), 2.95 (s, 3H), 2.07
(m, 1H), 1.91 (m, 1H), 1.82 (s, 3H), 1.71 (m, 3H), 1.66 (dd, 1H,
J ) 6.5, 12.1 Hz), 1.48 (s, 3H), 1.41 (s, 3H), 1.39 (m, 1H), 1.16
(d, 3H, J ) 6.3 Hz), 0.81 (s, 9H), 0.04 (s, 3H), -0.02 (s, 3H).
13C NMR (125.7 MHz, CDCl3): δ 170.0, 138.6, 138.5, 138.1,
137.0, 128.4, 128.3, 128.3, 128.2, 128.0, 127.9, 127.8, 127.6,
127.5, 127.4, 99.6, 96.1, 78.4, 76.2, 76.1, 74.2, 73.6, 72.8, 70.6,
69.6, 69.4, 68.0, 65.2, 62.7, 53.4, 52.7, 39.2, 36.8, 35.9, 33.6,
31.5, 29.0, 25.9, 23.0, 18.9, 17.9, 16.0, -4.0, -4.6. HRMS
Ack n ow led gm en t. Financial support from UCLA
and NIH Grant GM51095 are greatly appreciated. We
also thank Dr. J ane Strouse for helpful discussions and
support related to 2D NMR spectroscopy.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
all compounds reported (55 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
(FAB): M + H calcd 1046.5120, found 1046.5109. [R]D
+16.8° (c 0.0256, CHCl3).
)
J O9621534