Synthesis of both possible isomers of the northwest quadrant of Altromycin B

Article abstract of DOI:10.1021/jo034607k

The synthesis of the northwest quadrant of Altromycin B is described. The preparation of the two epimers at the quaternary carbon of the 6-deoxy-C-altrose moiety in the northwest quadrant is accomplished starting from D-glucose. A key step of our synthetic sequence is the formation of the C-glycoside linkage via the Ramberg-Baecklund reaction. Two different routes are explored, which differ mainly on the timing of the conversion of glucose to altrose, either before or after the preparation of the C-glycoside. The conformation behavior of variously substituted C-altropyranoside rings is also discussed.

Full text of DOI:10.1021/jo034607k

Syn th esis of Both P ossible Isom er s of th e Nor th w est Qu a d r a n t of
Altr om ycin B
Paolo Pasetto and Richard W. Franck*
Department of Chemistry, Hunter College of The City University of New York,
695 Park Avenue, New York, New York 10021
rfranck@hunter.cuny.edu
Received May 8, 2003
The synthesis of the northwest quadrant of Altromycin B is described. The preparation of the two
epimers at the quaternary carbon of the 6-deoxy-C-altrose moiety in the northwest quadrant is
accomplished starting from D-glucose. A key step of our synthetic sequence is the formation of the
C-glycoside linkage via the Ramberg-Ba¨cklund reaction. Two different routes are explored, which
differ mainly on the timing of the conversion of glucose to altrose, either before or after the
preparation of the C-glycoside. The conformation behavior of variously substituted C-altropyranoside
rings is also discussed.
In tr od u ction
There has been extensive work on the synthesis of
C-aryl glycosides of the “southeast” type,5 but in contrast,
there is to our knowledge only one report of an “aglycone”
synthesis (no carbohydrates) in the pluramycin family6
and no description of a synthesis of the novel “northwest”
C-glycoside.
Altromycin B (1) is an antitumor antibiotic produced
by an actinomycete (strain AB1246E-26) isolated from a
South African bushveld soil.1 Along with Altromycin B
eight other minor species (Altromycin A, C, D, E, F, G,
H, I) have been isolated from the fermentation broth
(Figure 1).2 Altromycins are members of the family of
pluramycin antibiotics. The aglycone chromophore is
common for all Altromycins A-I. Altromycins A-D and
G differ from one another in the sugar regions of the
molecule. Altromycins E and F are 13-deoxy. Altromycins
H and I lack the C-altrose moiety in the northwest
quadrant. Altromycin B showed activity against several
kinds of cancer. It has been demonstrated that Altromy-
cin B forms a complex with DNA by covalently binding
to the N-7 of guanine via nucleophilic attack of the
guanine’s nitrogen to the epoxide.3 A biosynthetic path-
way for Altromycin formation has been proposed.4
The structures of these molecules have been assigned
on the basis of their spectroscopic data, mainly by NMR.
No X-ray crystal structure is available. The stereochem-
istry at carbon 13 as well as of the epoxide moiety has
not been assigned. Moreover, it has not been determined
whether the carbohydrate moieties are present in the D
or L configuration.
Our goal was to achieve a synthetic route to the north-
west quadrant of Altromycin B (Figure 2). An important
purpose of our work was to produce materials of known
structure and stereochemistry so as to assign, for the first
time, the relative configuration at C-13 of the antibiotic
by comparison of its spectroscopic data to our synthetic
models. The assignment of the absolute configuration at
C-13 would not be possible by these means, since our data
would be compatible with either a D or L sugar.
Our synthetic plan had two elements: (i) the critical
C-glycoside bond-forming step would involve the Ram-
berg-Ba¨cklund reaction,7,8,9 and (ii) the carbohydrate
stereochemistry would be founded upon the well-known
conversion of glucose to altrose.10 The optimal timing of
the conversion, either before or after the C-glycoside
functionality and stereochemistry were established, was
not obvious to us; therefore both sequences outlined in
Scheme 1 were undertaken.
Resu lts a n d Discu ssion
Along with a commonly observed aryl-C-glycoside link-
age in the southeast, Altromycin B incorporates a rare
C-glycoside in its northwest quadrant. The R-6-deoxy-
altrose moiety is linked to the aglycone via a quaternary
carbon, and it assumes a flipped chair conformation.
We first describe our approach from altrose (Scheme
2), which started with the preparation of the partially
(5) Kaelin, D. E., J r.; Lopez, O. D.; Martin, S. F. J . Am. Chem. Soc.
2001, 123, 6937 and references therein.
(6) Hauser, F. M.; Rhee, R. P. J . Org. Chem. 1980, 45, 3061.
(7) Ramberg, L.; Ba¨cklund, B. Ark. Kemi Mineral. Geol. 1940, 13A,
no. 27, 1; Chem. Abstr. 1940, 34, 4725.
(8) For reviews on the Ramberg-Ba¨cklund reaction, see: (a) Bor-
dwell, F. G. In Organosulfur Chemistry; J anssen, M. J ., Ed.; Wiley:
New York, 1967, Chapter 16, p 271. (b) Paquette, L. A. Acc. Chem.
Res. 1968, 1, 209. (c) Paquette, L. A. Org. React. 1977, 25, 1. (d) Clough,
J . M. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Pattenden, G., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, Chapter
3.8. (e) Taylor, R. J . K. Chem. Commun. 1999, 217. (f) Paquette, L. A.
Synlett 2001, 1.
(1) (a) J ackson, M.; Karwowski, J . P.; Theriault, R. J .; Hardy, D. J .;
Swanson, S. J .; Barlow, G. J .; Tillis, P. M.; McAlpine J . B. J . Antibiot.
1990, 43, 223. (b) Brill, G. M.; McAlpine, J . B.; Whittern, D. N.; Buko,
A. M. J . Antibiot. 1990, 43, 229.
(2) Brill, G. M.; J ackson, M.; Whittern, D. N.; Buko, A. M.; Hill, P.;
Chen, R. H.; McAlpine, J . B. J . Antibiot. 1994, 47, 1160.
(3) Sun, D.; Hansen, M.; Clement, J . J .; Hurley L. H. Biochemistry
1993, 32, 8068.
(4) Hansen, M. R.; Hurley, L. H. Acc. Chem. Res. 1996, 29, 249.
10.1021/jo034607k CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/19/2003
8042
J . Org. Chem. 2003, 68, 8042-8060

Northwest Quadrant of Altromycin B
F IGURE 1. Structures of Altromycins.
R-6:â-6:7 ) 2:1:1. The products R-6 and â-6 could be
isolated as a mixture in 48% yield by crystallization from
methanol and could be used as a mixture for the next
step. Alternatively, the three products could be separated
by column chromatography. The presence of the ben-
zylidene protecting group was important in order to
ensure a rigid conformation of the pyranose ring and to
minimize the possibility of nucleophilic attack of the
methoxide at C-2.
The basic opening of the epoxides R- and â-6 by sodium
methoxide in DMSO at 95 °C proceeded via nucleophilic
axial attack of methoxide, producing the diaxial opening
of the epoxide in 80% yield.
The stereochemistry at the anomeric center of R- and
â-9 was assigned by measuring the 13C-1H coupling
constants, whose values were consistent with data re-
ported in the literature for similar models (1J CH(1) ) ∼170
Hz for R-9 and ∼162 Hz for â-9).13 After protection of the
hydroxyl group at position 2 with silyl ether (10, 90%
yield), the allyl ether was cleaved by palladium-catalyzed
tributyltin hydride reduction (11, 83%).14
The trichloroacetimidate 12 was prepared in 60%
yield15 and then employed in the synthesis of the thio-
altroside 14. Treatment of 12 with BF3‚OEt2 and benzyl
mercaptan produced the thioglycoside 13 in 95% yield
with the cleavage of the benzylidene, which could be
reinstalled in quantitative yield. The cleavage of the
benzylidene could be avoided by running the reaction at
low temperature. The two-step procedure (cleavage in the
glycosylation step, followed by reinstallation of the ben-
zylidene protecting group) was preferred because it
allowed an easier separation of 13 from the excess benzyl
mercaptan. In contrast, the similar Rf of benzyl mercap-
tan and 14 deriving from the temperature-controlled
glycosylation made the purification inefficient, and con-
sequently it was difficult to obtain a pure sample of 14
(in addition, the contamination with even small amounts
of benzyl mercaptan was very annoying, as a result of
the strong stench of this material).
F IGURE 2. The northwest quadrant of Altromycin B.
protected glucose 5 by treatment of R-D-glucose with allyl
alcohol at reflux in the presence of an acidic resin as
catalyst.11 We obtained a 3/2 mixture of R- and â-allyl
glucosides 4, which were protected as benzylidene de-
rivatives to afford the allyl 4,6-O-benzylidene-D-glucopy-
ranoside 5 in 60% yield over two steps.
By treating 5 with N-tosylimidazole and 2 equiv of
NaH, a mixture of products was obtained.12 The three
main products were isolated by column chromatography.
The structure of R-6 and â-6 was assigned after the basic
opening of the epoxide with sodium methoxide and
acetylation of the hydroxyl group. The ratio obtained was
(9) For applications of the Ramberg-Ba¨cklund reaction to the
synthesis of C-glycosides, see: (a) Belica, P. S.; Franck, R. W.
Tetrahedron Lett. 1998, 39, 8225. (b) Griffin, F. K.; Murphy, P. V.;
Paterson, D. E.; Taylor, R. J . K. Tetrahedron Lett. 1998, 39, 8179. (c)
Alcaraz, M.-L.; Griffin, F. K.; Paterson, D. E.; Taylor R. J . K.
Tetrahedron Lett. 1998, 39, 8183. (d) Yang, G.; Franck, R. W.; Byun,
H.-S.; Bittman, R.; Samadder, P.; Arthur, G. Org. Lett. 1999, 1, 2149.
(e) Yang, G.; Franck, R. W.; Bittman, R.; Samadder, P.; Arthur, G.
Org. Lett. 2001, 3, 197. (f) Pasetto, P.; Chen, X.; Drain, C. M.; Franck,
R. W. Chem. Commun. 2001, 81. (g) Griffin, F. K.; Paterson, D. E.;
Murphy, P. V.; Taylor, R. J . K. Eur. J . Org. Chem. 2002, 1305. (h)
Paterson, D. E.; Griffin, F. K.; Alcaraz, M.-L.; Taylor, R. J . K. Eur. J .
Org. Chem. 2002, 1323. (i) Ohnishi, Y.; Ichikawa, Y. Bioorg. Med.
Chem. Lett. 2002, 12, 997.
(10) (a) Kunz, H.; Weissmueller, J . Liebigs Ann. Chem. 1984, 66.
(b) Beau, J .-M.; Aburaki, S.; Pougny, J .-R.; Sinay¨, P. J . Am. Chem.
Soc. 1983, 105, 621.
(11) Bollenback, G. N. In Methods in Carbohydrate Chemistry;
Whistler, R. L., Wolfrom, M. L., Eds.; Academic Press Inc.: New York,
1963; Vol. II, p 326.
The oxidation of the sulfide 14 to sulfone 15 (95%) set
the stage for the key C-C bond-forming step. Thus, the
(13) Bock, K.; Pedersen, C. J . Chem. Soc., Perkin Trans. 2 1974,
293.
(14) (a) Four, P.; Guibe´, F. Tetrahedron Lett. 1982, 23, 1825. (b)
Guibe´, F.; Dangles, O.; Balavoine, G. Tetrahedron Lett. 1986, 27, 2365.
(c) Yin, H.; Franck, R. W.; Chen, S. L.; Quigley, G. J .; Todaro, L. J .
Org. Chem. 1992, 57, 644.
(15) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21.
(12) Hicks, D. R.; Fraser-Reid, B. Synthesis 1974, 203.
J . Org. Chem, Vol. 68, No. 21, 2003 8043

Pasetto and Franck
SCHEME 1. Tw o Rou tes to th e Nor th w est Qu a d r a n t of Altr om ycin Differ in g in th e Tim in g of th e
Glu cose-Altr ose Tr a n sfor m a tion
Ramberg-Ba¨cklund reaction of the sulfone 15 (Scheme
3) using Chan’s conditions,16,9 afforded the exo-glycal
16 in 70% yield. We obtained the Z isomer only, identi-
fied by NOE (6%) between the vinylic proton H-1 and
H-3.
Because of the low yield obtained for the required R-C-
glycoside from the altrose exo-glycal (16 or 19), we opted
for our alternate synthetic approach. Our exploratory
hydroborations of exo-glucal derivatives afforded reason-
able ratio of R/â products, in contrast to those described
above with exo-altral. Therefore, we decided to postpone
the double inversion route to the altrose configuration
until we first obtained an R-C-glucoside (Scheme 4).
Thus glucose pentaacetate was treated with excess
benzyl mercaptan in the presence of 1 equiv of BF3‚
OEt2.23 Deprotection of the acetates followed by instal-
lation of a benzylidene to protect positions 4 and 6
afforded 28 in a 96% overall yield for the three steps.
After protection of the hydroxyls at positions 2 and 3
as p-methoxybenzyl ethers (85%), the thioglucoside 29
was then oxidized to sulfone 30 (95% yield) and employed
in the Ramberg-Ba¨cklund reaction to obtain the exo-
glucal 31 in 70% yield. We obtained the Z isomer only,
as was determined by a NOESY analysis, which revealed
a NOE between the olefinic H-1 centered at 5.60 ppm
and the axial H-3 at 3.99 ppm.
The hydroboration/oxidation sequence17 applied to the
exo-glycal 16 afforded the C-glycosides 17 and 18 in 70%
yield and R/â ) ∼1/10 (Scheme 3). We hoped to achieve
higher selectivity toward the R product by delivery of the
borane from the axial hydroxyl group on C-3. The silyl
ether of 16 was therefore cleaved and the hydroboration
reaction on 19 was performed, unfortunately with no
improvement in the R/â ratio.18
The R configuration of the minor product 20 was con-
firmed by NOE (3%) between H-1 and H-6. The two
anomers 20 and 21 were separated by column chroma-
tography.
We tried to improve the R-selectivity by means of other
possible approaches. With the hope that a more flexible
ring could yield a more favorable ratio, the hydroboration
was conducted on 22, resulting however in the â-isomer
23 as the only product.
The hydroboration of the glucal 31 afforded a 3/1
mixture of the R- and â-C-glucosides 32 and 33 in 71%
combined yield. The two products were separated by flash
column chromatography on silica gel. The stereochem-
istry at the anomeric center of the two products can be
easily identified from the coupling constants between the
anomeric H-2 and the axial H-3: J 2,3 ) 4.9 Hz for 32,
J 2,3 ) 9.2 Hz for 33. We also observed two cross-peaks in
the NOESY spectrum of 32 which reveal an effect
between H-1 (centered at 5.11 ppm) and both H-4 (at 4.07
ppm) and H-6 (multiplet with H-5 at 3.74-3.70 ppm).
At this stage the stereochemistry at C-1 was assigned
by assuming a syn addition of borane to the double bond
and an oxidation with retention of configuration of the
organoborane intermediate. This assumption of stereo-
chemistry was confirmed later on in the synthesis.
The large coupling constant (8.5 Hz) between H-1 and
the anomeric H-2 of 32 indicates an anti relationship with
a ca. 180° dihedral angle between the two protons, sug-
gesting the favored conformation around the C-1-C-2
The hydride delivery by free hydroxyl groups complex-
ing an aluminum hydride to obtain a stereoselective
opening of epoxides has been described.19 So treatment
of exo-glycal 19 with dimethyldioxirane20 afforded the
epoxide 24,21 which was successively treated with Red-
Al with the hope that the axial hydroxyl group could
coordinate aluminum hydride and deliver a hydride from
the â-face of the anomeric carbon. Unfortunately this
reduction afforded the acyclic sugar derivative 25. This
can be rationalized by hydride delivery to C-1, the distal
epoxide carbon, which cleaves the epoxide to form a
hemiketal. Opening of the hemiketal and reduction of the
resulting ketone then affords the observed product.
Intramolecular delivery of hydride22 from a silyl ether
(26) was not practical because the silane was oxidized
by DMDO during the epoxide synthesis step.
(16) Chan, T.-L.; Fon, S.; Li, Y.; Man, T. O.; Poon C.-D. Chem.
Commun. 1994, 1771.
(17) RajanBabu, T. V.; Reddy, G. S. J . Org. Chem. 1986, 51, 5458.
(18) An unsuccessful attempt to achieve a hydroxyl-directed hy-
droboration has been reported: Smith, A. B., III; Yokoyama, Y.; Huryn,
D. M.; Dunlap, N. K. Tetrahedron Lett. 1987, 28, 3659.
(19) Kirshenbaum, K. S.; Sharpless, K. B. Chem. Lett. 1987, 11.
(20) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847.
(21) (a) Nicotra, F.; Panza, L.; Russo, G. Tetrahedron Lett. 1991,
32, 4035. (b) Link, J . T.; Danishefsky, S. J .; Schulte, G. Tetrahedron
Lett. 1994, 35, 9131.
(22) (a) McCombie, S. W.; Cox, B.; Lin, S. I.; Ganguly, A. K.; McPhail,
A. T. Tetrahedron Lett. 1991, 32, 2083. (b) McCombie, S. W.; Ortiz, C.;
Cox, B.; Ganguly, A. K. Synlett 1992, 541.
(23) (a) Ogawa, T.; Nakabayashi, S.; Sasajima, K. Carbohydr. Res.
1981, 95, 308. (b) Matsui H.; Furukawa, J .; Awano, T.; Nishi, N.;
Sakairi, N. Chem. Lett. 2000, 326.
8044 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
SCHEME 2 a
a
Reagents and conditions: (a) allyl alcohol, acidic resin, 70 °C; (b) dimethoxytoluene, TsOH, CH3CN, 60% for 2 steps; (c) N-tosylimidazole,
NaH, DMF, 6: 48%, 7: 16%; (d) NaOMe, DMSO/MeOH, 95 °C, 80%; (e) Ac2O, DMAP, EtOAc; (f) TBDMSCl, imidazole, DMF, 90%; (g)
ZnCl2, Pd(PPh3)4, Bu3SnH, THF, 83%; (h) Cl3CCN, NaH, CH2Cl2, 60%; (i) BnSH, BF3‚OEt2, CH2Cl2, -78 °C to rt, 95%; (j) dimethoxytoluene,
TsOH, CH3CN; (k) MMPP, THF/EtOH/H2O, 60 °C, 95%.
bond described in Scheme 4, structure 32. The alternative
syn relationship between H-1 and H-2, consistent with
the value of the coupling constant, is not favored by steric
considerations since it would involve an eclipsed confor-
mation. Also the value observed for the coupling constant
J 1,2 ) 9.2 Hz in 33 suggests the conformational arrange-
ment depicted in Scheme 4.24
formation due to steric congestion of the axial anomeric
group.
The hydroxyl group of 32 was protected as its SEM
ether (34, 95%),25 and the PMB ethers were cleaved with
DDQ (35, 82%).26 The coupling constants J 2,3 ) J 3,4 ) 3.1
Hz, measured for the triplet corresponding to H-3 in 34
suggest a distortion of the chair to a boat conformation
larger than that in 32, due to the presence of the more
sterically demanding SEM ether. The release of steric
congestion in 35 after the deprotection of the PMB ethers
results in a less distorted chair conformation as confirmed
by the coupling constants J 3,4 ) J 4,5 ) J 5,6 ) 9.2 Hz,
typical of an axial relationship among H-3, H-4, and H-5.
1
The H NMR spectrum (25 °C, CDCl3) of 32 shows a
well-defined triplet at 4.07 ppm for H-4 in which the
coupling constant J ) 7.6 Hz appears a little too small
for a diaxial interaction (normally ∼9 Hz) among H-3,
H-4, and H-5, suggesting a distortion of the chair con-
(24) (a) Goekjian, P. G.; Wu, T.-C.; Kishi, Y. J . Org. Chem. 1991,
56, 6412. (b) Wang, Y.; Goekjian, P. G.; Ryckman, D. M.; Miller, W.
H.; Babirad, S. A.; Kishi, Y. J . Org. Chem. 1992, 57, 482. (c) Kishi, Y.
Pure Appl. Chem. 1993, 65, 771.
(25) Lipshutz, B. H.; Pegram, J . J . Tetrahedron Lett. 1980, 21, 3343.
(26) Zhang, Z.; Magnusson, G. J . Org. Chem. 1996, 61, 2394.
J . Org. Chem, Vol. 68, No. 21, 2003 8045

Pasetto and Franck
SCHEME 3 a
a
Reagents and conditions: (a) CBr2F2, KOH on Al2O3, CH2Cl2/t-BuOH, 70%; (b) BH3, THF, then H2O2, KOH, H2O, 70%; (c) n-Bu4NF,
THF; (d) DMDO, CH2Cl2; (e) Red-Al, THF.
The C-glucoside 35 was converted to epoxide in 95%
yield.12 Two products, 2,3-anhydro-C-mannoside deriva-
tive 36 and 2,3-anhydro-C-alloside 37, were obtained in
4/1 ratio and were separated by column chromatography.
The anomeric proton H-2 of the major product 36 is a
doublet centered at 4.22 ppm with a coupling constant
J 2,3 ) 0 Hz, consistent with a dihedral angle close to 90°
(see projection a, Figure 3), whereas in the epoxide 37
the anomeric proton H-2 is a doublet of doublets centered
at 4.11 ppm with a coupling constant J 2,3 ) 3.1 Hz. Such
a coupling constant is probably due to a staggered
relationship between H-2 and H-3 arising from a pseudo-
boat conformation of the sugar ring (projection b, Figure
3). The alternative possibility for 37 is a pseudo-chair
conformation, which can be ruled out since a larger coup-
ling constant would be expected from the eclipsed rela-
tionship between H-2 and H-3 (projection c, Figure 3).
correct functionalities for Altromycin at positions 3 and
4. Lower temperatures resulted in a sluggish reaction.
Deprotection of the SEM ether in 38 with tetrabutyl-
ammonium fluoride yielded a product with NMR data
identical to that of 20, confirming the R-stereochemistry
assigned previously.
After the cleavage of the benzylidene protecting group
(85% yield) the NMR spectrum of 39 showed a coupling
constant J 2,3 ) J 3,4 ) 7.0 Hz, which is not consistent with
either one of the two possible chair conformations. The
NOESY spectrum of 39 shows two diagnostic cross-peaks,
one revealing an effect (2% NOE) between H-1 and H-6,
consistent with the conformation 39′, and a second one
revealing an effect (2% NOE) between H-3 and OH-5,
which indicates the presence of the chair conformation
39′′. These NOESY signals would not be compatible with
boat or skew conformations, even if the presence of such
conformations could not be ruled out from a possible
The configuration of the epoxide 36 was confirmed by
basic opening with sodium methoxide (ca. 2 M in metha-
nol) at 120 °C (sealed tube), which gave the altrose
derivative 38 in quantitative yield, resulting from the
diaxial opening of the epoxide with the installation of the
1
dynamic equilibrium. Furthermore, low-temperature H
and 13C NMR spectra show a clear broadening and
shifting of signals. These observations indicate the pres-
ence of an equilibrium between the two forms 39′ and
8046 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
SCHEME 4 a
a
Reagents and conditions: (a) BnSH, BF3‚OEt2, CH2Cl2; (b) NaOMe, MeOH; (c) dimethoxytoluene, TsOH, CH3CN, 96% for 3 steps; (d)
PMBCl, NaH, THF/DMF, 85%; (e) MMPP, THF/EtOH/H2O, 60 °C, 95%; (f) CBr2F2, KOH on Al2O3, CH2Cl2/t-BuOH, 70%; (g) BH3, THF,
0 °C to rt, then H2O2, H2O, KOH, 71%; (h) SEMCl, (i-Pr)2NEt, CH2Cl2, 95%; (i) DDQ, CH2Cl2/H2O, 82%; (j) N-tosylimidazole, NaH, DMF,
95%; (k) NaOCH3, CH3OH, 120 °C, quantitative; (l) TsOH, CH3OH; (m) Ac2O, EtOAc, DMAP.
calculate an equilibrium constant from the integration
of the signals at low temperature. An approximate
equilibrium constant for this equilibrium, K ) 2 ( 1,
could be extrapolated by comparing the experimental
coupling constant with the expected coupling constants
of the two chair-conformers (assuming that the popula-
tions of other conformers be negligible and the two chairs
not distorted).
F IGURE 3. Projection along the C-3-C-2 bond of 36 assum-
ing a chair conformation of the sugar ring (a) and 37 in a boat
conformation (b) and in a chair conformation (c).
A side product of the acidic cleavage of the benzylidene
of 38 arose from the deprotection of the SEM ether (40,
15%). Such side reaction could be limited but not avoided
by carefully monitoring the reaction by TLC. In any
39′′. Unfortunately, the coalescence temperature and a
separation of the signals corresponding to each conformer
could not be reached and therefore it was not possible to
J . Org. Chem, Vol. 68, No. 21, 2003 8047

Pasetto and Franck
SCHEME 5 a
a
Reagents and conditions: (a) I2, PPh3, imidazole, THF, reflux, 85%; (b) AIBN, Bu3SnH, PhMe, reflux, 87%; (c) TFA, CH2Cl2, quantitative;
(d) Bu3SnH, AIBN, PhMe, reflux, 75%; (e) dimethoxytoluene, cat. TsOH, CH3CN; (f) DDQ, CH2Cl2, 77%; (g) TBDMSCl, imidazole, DMF,
93%; (h) Ph3PdCH2, THF, -10 °C to rt; (i) Nysted reagent, TiCl4, THF/CH2Cl2.
event, product 40 could be employed in the successive
steps. Longer reaction times afforded only product 40 in
quantitative yield.
The product 45 was obtained by acidic deprotection of
the SEM ether in quantitative yield30 or as an alterna-
tive via selective iodination of the primary hydroxyl
group in 40 (44, 85% yield), followed by radical deiodi-
nation (45, 75%). Although this last route was shorter
by one step (the deprotection of both benzylidene and
SEM was achieved in a single step from 38) and conse-
quently preferred when we scaled up the reaction, the
two-step deprotection was preferred in order to obtain
an analytically pure sample, since the purification of 44
from the triphenylphosphine oxide byproduct proved to
be unsuccessful by conventional column chromatography.
Our effort to use polymer-supported triphenylphos-
phine in the transformation from 40 to 44 was not
successful.
Interestingly, the acetylation of the C-glycoside 40,
which assumes a 1C4-type preferred conformation27 (as
evident from the coupling constants J 2,3 ) J 3,4 ) 7.6 Hz
and J 4,5 ) J 5,6 ) 3.2 Hz), resulted in the flipping of the
4
ring in 41 to a C1-type conformation (J 2,3, J 3,4, J 4,5 ) 2.4-
3.6 Hz and J 5,6 ) 9.2 Hz). Deprotection of the acetates
with catalytic sodium methoxide in 41 afforded 40
without any trace of epimerization at C-1.
The selective iodination of the primary hydroxyl group
of 39 (Scheme 5) was achieved in 85% yield.28 This
product probably also consists of an equilibrium between
the two chair conformations, as suggested by the coupling
constant J 2,3 ) J 3,4 ) 7.3 Hz. Furthermore, for 42
broadening and shifting of the 1H NMR signals were
observed at low temperatures.
The radical deiodination of 42 afforded the 6-deoxy
derivative 43 (87% yield),29 whose coupling constants
J 2,3 ) J 3,4 ) 8.5 Hz suggest a flipped 1C4-type confor-
mation.
At this stage it was possible to confirm the stereo-
chemistry at C-1 obtained in the hydroboration step from
31 to 32 by making the benzylidene derivative 46. The
NOESY spectrum indeed reveals an axial relationship
among H-1, H-3 and H-8.
(28) (a) Garegg, P. J .; Samuelsson, B. Chem. Commun. 1979, 978.
(b) Garegg, P. J .; Samuelsson, B. J . Chem. Soc., Perkin Trans. 1 1980,
2866. (c) Spak, S.; Martin, O. R. Tetrahedron 2000, 56, 217.
(29) Neumann, W. P. Synthesis 1987, 665.
(30) J ansson, G.; Frejd, T.; Kihlberg, J .; Magnusson G. Tetrahedron
Lett. 1988, 29, 361.
(27) The notation we adopted to describe the conformation of
pyranose rings (1C4 or 4C1) refers to the numbering commonly employed
for O-glycosides, where the anomeric carbon is C-1.
8048 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
SCHEME 6 a
a
Reagents and conditions: (a) OsO4, MMNO, acetone/H2O/t-BuOH, 82%; (b) Kirschning’s resin, CH2Cl2, cat. TEMPO, quantitative; (c)
I2, NaOH, MeOH, >95%; (d) TBAF, AcOH, THF, >93%; (e) dimethoxytoluene, cat. TsOH, CH3CN; (f) DIBAL-H, CH2Cl2.
Several oxidizing reagents were explored for the oxida-
tion of the benzylic alcohol 45 to ketone (notably, MnO2,31
4-(dimethylamino)pyridinium chlorochromate,32 BaMnO4/
CuSO4/Al2O3,33 NBS), but all proved to be either not
reactive or to afford a sluggish reaction. DDQ was the
only oxidant that gave satisfactory results (77% yield).
The free hydroxyl groups in positions 3 and 5 of 47
were then protected as silyl ethers in 93% yield. The
acidic conditions employed in the reaction. This side
product can be minimized by running the reaction under
rigorously anhydrous conditions and by optimizing the
reaction time. It is interesting to notice the opposite
preferred conformations assumed by the pyranose ring
in 48 (4C1-type, J 2,3 ) 3.0 Hz, J 5,6 ) 7.9 Hz) and R-49
(1C4-type, J 3,4 ) J 4,5 ) 7.0 Hz and J 5,6 ) 3.0 Hz).
The dihydroxylation of R-49 with osmium tetroxide35
gave a separable mixture of the two epimers at C-2 52
and 53 in 4/1 ratio and 82% combined yield (Scheme 6).
Interestingly the difference in a single stereocenter
between the two C-glycosides 52 and 53 results in
completely different conformational behaviors: the
4C1-type is the preferred conformation for major isomer
52 (J 3,4 ) 0 Hz, J 4,5 ) J 5,6 ) 3.2 Hz and J 6,7 ) 9.2 Hz)
values of the coupling constants J 2,3 ) 2.5 Hz and J 5,6
)
7.9 Hz for the product 48 suggest a preferred 4C1-type
conformation. Efforts to install the methylene via Wittig
procedures were unsuccessful as a result of epimerization
at the anomeric center (R- and â-49) and competitive
elimination to form the glycal 50.
We consequently opted to employ the Nysted reagent,34
which gave a satisfactory yield (R-49, 73%), with concur-
rent formation of the byproduct 51 (21%), derived by
addition of water to the double bond catalyzed by the
1
and C4-type is preferred for 53 (J 3,4 ) J 4,5 ) 9.2 Hz, J 5,6
) J 6,7 ) 2.4 Hz). The configuration at the quaternary
centers was assigned later in the synthesis.
The oxidation of vicinal diols is reported to proceed
with low yields, as a result of competitive cleavage of the
C-C bond to form a ketone (48 in our case). This
fragmentation of the molecule is particularly accentuated
when metal-containing oxidizers are employed. Methods
involving IBX,36 alkali hypochlorites,37 and more recently
(31) Fatiadi, A. J . Synthesis 1976, 65.
(32) Guziec, F. S., J r.; Luzzio, F. A. J . Org. Chem. 1982, 47, 1787.
(33) Kim, K. S.; Chung, S.; Cho, I. H.; Hahn, C. S. Tetrahedron Lett.
1989, 30, 2559.
(34) (a) Watson, A. T.; Park, K.; Wiemer, D. F. J . Org. Chem. 1995,
60, 5102. (b) Nysted, L. N. U.S. Patent 3,865,848, 1975; Chem. Abstr.
1976, 85, 94618n. (c) Franck, R. W.; Marzabadi, C. H. J . Org. Chem.
1998, 63, 2197. (d) Matsubara, S.; Sugihara, M.; Utimoto, K. Synlett
1998, 313.
(35) Schro¨der, M. Chem. Rev. 1980, 80, 187.
J . Org. Chem, Vol. 68, No. 21, 2003 8049

Pasetto and Franck
1
F IGURE 4. Comparison of H NMR spectra (CDCl3, 500 MHz) of Altromycin B (1) with those of 2 and 3.
TABLE 1. Com p a r ison of 13C NMR Sh ift Va lu es
betw een Altr om ycin B a n d th e Tw o Mod els 2 a n d 3
chlorite/hypochlorite catalyzed by TEMPO have been
proposed,38 but when we tested them they did not give
very satisfactory results in terms of yields. Therefore we
were particularly glad when we observed that the oxida-
tion of 52 and 53 employing the polymer-supported
bromite(I) complex recently described by Kirschning39
gave quantitative yields. The aldehydes 54 and 55 could
be isolated without further purification and directly
employed in the next step. Both products 54 and 55
Altromycin B
2
3
C-13
C-18
C-19
C-2′
C-3′
C-4′
C-5′
C-6′
CH3-2′
OCH3-4′
81.16
170.8
52.85
74.02
69.15
80.43
68.18
73.88
14.29
58.14
79.96
173.68
53.40
73.48
69.16
80.84
67.39
77.05
15.14
58.12
78.56
173.27
53.16
73.43
69.85
81.61
67.09
75.59
14.54
58.10
4
assume a C1-type conformation.
The oxidation to esters of 54 and 55 was achieved in
one step and in ca. 95% yield by alkaline iodine oxida-
tion40 employing an inverse addition (alkaline solution
added to the mixture of iodine and starting material).
The TBDMS ethers were then cleaved by action of
fluoride in the presence of acetic acid to avoid the
hydrolysis of the esters (2 and 3).
The stereochemistry at the quaternary center C-2
(corresponding to C-13 of Altromycin B) was assigned by
synthesizing the benzylidene derivative 58 from 2, fol-
lowed by reduction of the ester to alcohol with DIBAL-H
(59). The NOESY spectrum clearly shows two cross-
peaks, which evidence an effect between the benzylidene
H-9 and, respectively, one proton of the methylene C-1
and H-4.
data we recorded for the northwest quadrant of Altro-
mycin B in order to assign the stereochemistry at the
quaternary C-13.41 As expected little information about
the configuration at that center was obtained from the
1H NMR spectra (Figure 4) since the differences of proton
chemical shifts of both synthetic isomers show no trend
compared to the corresponding protons in Altromycin B.
A way to quantify the discrepancy is to calculate the
average of the absolute values of the differences between
the chemical shift corresponding to each proton of the
two models and Altromycin B. By means of this method
we obtain an average difference in chemical shift ∆ )
1.72 for 2 and ∆ ) 1.78 for 3.
Com p a r ison of NMR Da ta of th e Syn th etic Mod -
els w ith Altr om ycin B. Both proton and carbon spectral
data of the two models 2 and 3 were compared with the
Unfortunately the comparison of 13C chemical shifts
was not helpful either. Table 1 lists the values of chemical
shifts for relevant carbons of Altromycin B and the two
(36) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35, 8019.
(37) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. J . Org. Chem.
1989, 54, 2970.
(38) Aladro, F. J .; Guerra, F. M.; Moreno-Dorado, F. J .; Bastamante,
J . M.; J orge, Z. D.; Massanet, G. M. Tetrahedron Lett. 2000, 41, 3209.
(39) Sourkouni-Argirusi, G.; Kirschning, A. Org. Lett. 2000, 2, 3781.
(40) Yamada, S.; Morizono, D.; Yamamoto, K. Tetrahedron Lett.
1992, 33, 4329.
(41) In this section the numbering we refer to is the one adopted
for Altromycin B (Figure 1).
8050 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
SCHEME 7 a
F IGURE 5. Graphical representation of the differences in 13C
NMR shift values between Altromycin B and the two models
2 and 3.
a
Reagents and conditions: (a) 4-bromobenzaldehyde dimethyl
acetal, TsOH, CH3CN.
models. Figure 5 exemplifies the trend of the differences
in chemical shifts between Altromycin B and each one
of the two models.42 The average of the absolute values
of the differences in chemical shifts between Altromycin
B and 2 (∆ ) 0.104) and 3 (∆ ) 0.119) are too close and
do not allow us to assign the stereochemistry at C-13.
We also prepared the benzylidene derivatives 60 and
61 of the two model compounds and the analogue 62 of
Altromycin B (Scheme 7), with the hope that circular
dichroism could give us some information about the
stereochemistry at C-13, based on a possible Cotton effect
associated with the optically active electronic transitions
derived from the asymmetry induced by the presence of
two chromophores in an asymmetric environment.43
Anticipating the bathochromic effect on the UV spectrum,
para-subsituted bromo benzylidene was chosen, also with
the expectation that the presence of a heavy atom could
be helpful in the resolution of eventual crystal structure
of the Altromycin B derivative.
Unfortunately the circular dichroism gave ambiguous
results, probably because of the presence of two different
chromophores, without allowing us to assign the config-
uration of the C-13. Furthermore, a complete and un-
ambiguous assignment of the structure of the derivative
62 based on 1H and 13C NMR spectra was not possible
because of the complexity of the system, but the mass
spectrum was in full agreement with the proposed
structure. Under the acidic conditions used for ben-
zylidene formation the 2,6-dideoxy altrose moiety in the
southeast quadrant was cleaved.
F IGURE 6. Chair conformations of C-altrosides.
Rin g Con for m a tion of C-Altr osid es. Throughout
the synthesis of the northwest quadrant of Altromycin
B we found it interesting to analyze the conformational
features of the pyranose rings (Figure 6), which we tried
to explain as due mostly to steric effects. We observed
that even minimal differences in the structure brought
about contrasting conformational behaviors, as is evident
from the two different conformations assumed by the two
epimers at C-1, 52 and 53. The conformational properties
of each molecule were determined mostly by the values
of the coupling constants and in some cases with the
support of NOESY spectra. In Table 2 the diagnostic
coupling constants of relevant compounds are reported.
Each molecule is listed in the preferred conformation
assumed on the basis of the values of the coupling
constants. In the cases in which equilibrium between the
two chair conformations could be assumed the conforma-
tion represented is the one that could be supposed to have
larger population by analysis of the coupling constants.
All of our efforts to crystallize 62 as well as Altromycin
B itself were unsuccessful.
Con clu sion s
The Ramberg-Ba¨cklund reaction proved to be a valu-
able synthetic tool for the preparation of C-glycosides via
exo-glycal intermediates, its main advantages being the
simple reaction conditions, easy accessibility of the
thioglycoside starting materials, and the inexpensive
(42) (a) Kobayashi, Y.; Lee, J .; Tezuka, K.; Kishi, Y. Org. Lett. 1999,
1, 2177. (b) Lee, J .; Kobayashi, Y.; Tezuka, K.; Kishi, Y. Org. Lett. 1999,
1, 2181.
(43) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy-
Exciton Coupling in Organic Stereochemistry; University Science
Books: Mill Valley, CA, 1983.
J . Org. Chem, Vol. 68, No. 21, 2003 8051

Pasetto and Franck
TABLE 2. Cou p lin g Con sta n t Va lu es a n d P r efer r ed
Con for m a tion in Va r ia bly Su bstitu ted C-Altr osid es
Exp er im en ta l Section
The assignment of proton and carbon NMR peaks was
supported by routine 1H-1H COSY and HSQC spectra and for
some compounds by DEPT and NOESY spectra.
preferred
conformation
compound
J 1,2
J 2,3
J 3,4
J 4,5
20
38
41
39
42
43
45
46
47
48
49
52
53
54
55
56
57
2
4C1
4C1
4C1
1C4
1C4
1C4
1C4
1C4
1C4
4C1
1C4
4C1
1C4
4C1
4C1
4C1
4C1
1C4
1C4
0
3.1
2.4
4.0
3.4
9.8
9.8
9.2
Allyl-2,3-a n h yd r o-4,6-O-b en zylid en e-r-D-m a n n op yr a -
n osid e (r-6), Allyl-2,3-a n h yd r o-4,6-O-b en zylid en e-â-D-
m a n n op yr a n osid e (â-6), a n d Allyl-2,3-a n h yd r o-4,6-O-
ben zylid en e-â-D-a llop yr a n osid e (7).12 Sodium hydride (60%
in mineral oil, 1.1 g, 27 mmol) was washed free of oil with
pentane. Dry DMF (30 mL) was added, followed by the
addition of allyl 4,6-O-benzylidene-D-glucopyranoside (4.16 g,
13.5 mmol) dissolved in dry DMF (30 mL). The mixture was
stirred at room temperature for 0.5 h under N2, then N-tosyl-
imidazole (3.2 g, 14.4 mmol) was added, and the mixture was
stirred for 4 h. The mixture was poured into iced water (500
mL), and the crystals were under reduced pressure. The
product R-6 containing variable amounts of â-6 was purified
by crystallization from methanol (1.82 g, 48%) as a white solid.
Alternatively the reaction mixture was extracted with EtOAc/
sat. NH4Cl and purified by flash column chromatography
(SiO2, petroleum ether, 5% EtOAc). The products R-6, â-6, and
7 were isolated in the ratio 2:1:1. R-6: Rf 0.44 (PE/EtOAc, 8/2);
1H NMR (500 MHz, CDCl3) δ 7.52-7.48 (2H, m), 7.42-7.36
(3H, m), 5.94 (1H, ddt, J ) 17.1, 10.4, 5.9 Hz, H-8), 5.57 (1H,
s, H-10), 5.34 (1H, dd, J ) 17.1, 1.4 Hz, H-9a), 5.25 (1H, dd, J
) 10.4, 1.4 Hz, H-9b), 5.06 (1H, s, H-1), 4.30-4.23 (2H, m,
H-7a and H-6eq), 4.10 (1H, dd, J ) 12.8, 6.4 Hz, H-7b), 3.78
(1H, dt, J ) 9.9, 4.3 Hz, H-5), 3.72 (1H, t, J ) 10.1 Hz, H-6ax),
3.68 (1H, d, J ) 9.2 Hz, H-4), 3.49 (1H, d, J ) 3.7, H-2 or
H-3), 3.21 (1H, d, J ) 3.7 Hz, H-3 or H-2); 13C NMR (75 MHz,
CDCl3) δ 137.22, 133.77, 129.31, 128.42, 126.28, 117.90 (C-9),
102.55 (C-10), 95.26 (C-1), 75.13 (C-5), 69.57 (C-6), 69.16
(C-7), 62.03 (C-4), 54.04 (C-2 or C-3), 50.87 (C-3 or C-2). â-6:
2.4
7.0
7.3
8.5
8.5
4.0
7.0
7.3
8.5
8.5
9.3
7.3
4.9
7.0
3.7
9.2
3.4
4
∼0
∼3.1
3.1
3.1
3.7
2.4
3.0
3.1
2.4
3
2.7
3.2
3.2
3.2
3.1
4.3
1.8
1.8
6.7
2.5
7.0
0
9.2
0
3
1.3
0
7.9
4.3
9.2
2.4
9.6
7
8.9
8.9
1.6
3.2
3.2
9.1
9.5
9.2
9.5
3
reagents employed. Many other approaches to C-glyco-
sides have been described,44 and it is our opinion that
each method presents advantages and disadvantages,
making none of them superior to the others. Nevertheless
we think that the attractive feature of the Ramberg-
Ba¨cklund route to C-glycosides is its generality, because
in principle it can be applied to the synthesis of virtually
any C-glycoside in usually high yield.
1
The exo-glycal product of the Ramberg-Ba¨cklund
reaction can be easily converted to â-C-glycoside by
catalytic or ionic hydrogenation or further functionalized
to more complexly substituted â-C-glycoside by addition
reactions to the double bond. exo-Glycals have been used
successfully by others to prepare a variety of C-glyco-
sides.45 Conversion of exo-glycals to R-C-glycosides has
proven to be more problematic, since in our cases even
the most stereoselective hydroboration yielded a mixture
of R/â products that never exceeded a 3/1 ratio. A
specialized approach to R-C-galactosides that involves an
internal delivery of hydride has been achieved by our
group,9d but the applicability of this method to sugars
other than galactose has not been demonstrated.
The synthesis of the two epimers at C-13 of the
northwest quadrant of Altromycin B demonstrates that
the Ramberg-Ba¨cklund reaction can be efficiently em-
ployed in the preparation of complex natural products
containing C-glycosides. Unfortunately the spectroscopic
data of our synthetic models did not give definitive
information regarding the relative stereochemistry of the
quaternary C-13 of Altromycin B. Thus, the complete
structure proof of Altromycin awaits either a synthesis
that incorporates more structural features of the natural
material than our model or a diffractable crystal, which
has eluded us to date.
Rf 0.30 (PE/EtOAc, 8/2); H NMR (500 MHz, CDCl3) δ 7.53-
7.49 (2H, m), 7.43-7.37 (3H, m), 5.97 (1H, ddt, J ) 17.1, 10.6,
6.4 Hz, H-8), 5.58 (1H, s, H-10), 5.36 (1H, d, J ) 17.1 Hz, H-9a),
5.26 (1H, d, J ) 17.1 Hz, H-9b), 5.09 (1H, s, H-1), 4.45 (1H,
dd, J ) 12.8, 4.9 Hz, H-7a), 4.29 (1H, dd, J ) 10.5, 4.6 Hz,
H-6eq), 4.20 (1H, dd, J ) 12.8, 6.4 Hz, H-7b), 3.82 (1H, t, J )
10.5 Hz, H-6ax), 3.78 (1H, d, J ) 9.5 Hz, H-4), 3.53 (1H, d, J
) 3.7 Hz, H-2 or H-3), 3.36 (1H, dt, J ) 9.8, 4.6 Hz, H-5), 3.29
(1H, d, J ) 3.7 Hz, H-3 or H-2); 13C NMR (75 MHz, CDCl3) δ
137.12, 133.71, 129.38, 128.47, 126.26, 118.17 (C-9), 102.63
(C-10), 97.93 (C-1), 74.84 (C-4), 70.51 (C-7), 69.48 (C-6), 68.76
(C-5), 55.29 (C-2 or C-3), 51.16 (C-3 or C-2). 7: Rf 0.38
(PE/EtOAc, 8/2); 1H NMR (500 MHz, CDCl3) δ 7.52-7.49 (2H,
m), 7.40-7.35 (3H, m), 5.94 (1H, ddt, J ) 16.5, 11.0, 5.5 Hz,
H-8), 5.58 (1H, s, H-10), 5.34 (1H, dd, J ) 17.7, 1.2, Hz, H-9a),
5.25 (1H, d, J ) 10.4 Hz, H-9b), 5.04 (1H, s, H-1), 4.35 (1H,
dd, J ) 12.4, 5.5 Hz, H-7a), 4.27-4.24 (1H, m, H-6eq), 4.14-
4.09 (2H, m, H-5, H-7b), 3.75-3.71 (2H, m, H-4, H-6ax), 3.54
(1H, d, J ) 4.3 Hz, H-2 or H-3), 3.38 (1H, d, J ) 4.3 Hz, H-3
or H-2); 13C NMR (75 MHz, CDCl3) δ 137.26, 133.62, 129.34,
128.45, 126.41, 118.13, 102.91, 96.40, 77.83 (C-5), 70.47 (C-7),
69.28 (C-6), 61.06 (C-4), 55.70, 51.56.
Allyl-3-O-m et h yl-4,6-O-b en zylid en e-r-D-a lt r op yr a n o-
sid e (r-8) a n d Allyl-3-O-m eth yl-4,6-O-ben zylid en e-â-D-
a ltr op yr a n osid e (â-8). To a 0.2 M solution of R-6 or â-6 in
dry DMSO were added magnesium methoxide (ca. 2 M in
methanol, 1.2 equiv) and sodium methoxide (ca. 3 M in
methanol, 1.5 equiv). The mixture was stirred at 95 °C under
N2 for 4 h, then it was allowed to cool at room temperature,
quenched with saturated aqueous NH4Cl, and extracted with
EtOAc. The product R-8 (89%) or â-8 (60%) was isolated by
flash column chromatography (SiO2, petroleum ether, 25%
EtOAc) as pale yellow oils. R-8: 1H NMR (500 MHz, CDCl3) δ
7.52-7.48 (2H, m), 7.39-7.34 (3H, m), 5.92 (1H, ddt, J ) 17.4,
10.6, 4.9 Hz, H-8), 5.56 (1H, s, H-10), 5.33 (1H, dd, J ) 17.4,
1.5 Hz, H-9a), 5.22 (1H, d, J ) 10.6 Hz, H-9b), 4.76 (1H, s,
H-1), 4.36 (1H, dt, J ) 10.1, 5.2 Hz, H-5), 4.30 (1H, dd, J )
10.1, 5.2 Hz, H-6eq), 4.24 (1H, dd, J ) 13.1, 4.9 Hz, H-7a),
4.10-4.04 (2H, m, H-2 and H-7b), 4.02 (1H, dd, J ) 9.8, 2.8
(44) (a) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides; Elsevier
Science Publishers: Amsterdam, 1995. (b) Postema, M. H. D. C-
Glycoside Synthesis; CRC Press: Boca Raton, FL, 1995. (c) Beau, J .-
M.; Gallagher, T. Topics Curr. Chem. 1997, 187, 1. (d) Nicotra, F.
Topics Curr. Chem. 1997, 187, 55. (e) Sinay¨, P. Pure Appl. Chem. 1997,
69, 459. (f) Du, Y.; Linhardt, R. J . Tetrahedron 1998, 54, 9913.
(45) (a) J ohnson, C. R.; J ohns, B. A. Synlett 1997, 1406. (b) Liu, H.;
Smoliakova I. P.; Koikov, L. N. Org. Lett. 2002, 4, 3895. (c) Yang, W.-
B.; Yang, Y.-Y.; Gu, Y.-F.; Wang, S.-H.; Chang, C.-C.; Lin, C.-H. J .
Org. Chem. 2002, 67, 3773.
8052 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
Hz, H-4), 3.78-3.72 (2H, m, H-3 and H-6ax), 3.57 (3H, s,
OCH3), 1.93 (1H, broad s, OH); 13C NMR (75 MHz, CDCl3) δ
137.70, 133.95, 129.14, 128.35, 126.36, 117.78 (C-9), 102.56
(C-10), 99.53 (C-1), 78.15 (C-3), 77.44 (C-4), 69.81 (C-2), 69.52
(C-6), 68.51 (C-7), 60.09 (OCH3), 59.00 (C-5). â-8: 1H NMR
(500 MHz, CDCl3) δ 7.51-7.47 (2H, m), 7.39-7.33 (3H, m),
5.92 (1H, ddt, J ) 17.4,10.7, 5.8 Hz, H-8), 5.53 (1H, s, H-10),
5.31 (1H, dd, J ) 17.4, 1.2 Hz, H-9a), 5.23 (1H, d, J ) 10.4
Hz, H-9b), 4.85 (1H, s, H-1), 4.39 (1H, dd, J ) 12.5, 5.2 Hz,
H-7a), 4.33 (1H, dd, J ) 10.1, 4.9 Hz, H-6eq), 4.14 (1H, dd, J
) 12.5, 6.4 Hz, H-7b), 4.03 (1H, dd, J ) 9.8, 2.5 Hz, H-4), 3.97
(1H, dt, J ) 10.1, 4.9 Hz, H-5), 3.94 (1H, d, J ) 2.7 Hz, H-2),
3.84 (1H, t, J ) 2.7 Hz, H-3), 3.79 (1H, t, J ) 10.1 Hz, H-6),
3.56 (3H, s, OCH3); 13C NMR (75 MHz, CDCl3) δ 137.71,
133.70, 129.07, 128.32, 126.27, 118.04 (C-9), 102.43 (C-8), 97.37
(C-1), 77.86 (C-3 or C-4), 77.66 (C-4 or C-3), 70.61 (C-2), 70.26
(C-7), 69.37 (C-6), 63.58 (C-5), 60.19 (OCH3).
0.92 (9H, s, TBDMS), 0.11 (3H, s, TBDMS), 0.10 (3H, s,
TBDMS); 13C NMR (75 MHz, CDCl3) δ 137.92, 134.18, 129.12,
128.37, 126.45, 117.61 (C-9), 102.56 (C-10), 99.80 (C-1), 79.02
(C-3), 77.61, 70.78, 69.67 (C-6), 68.28 (C-7), 60.20 (OCH3),
58.87 (C-5), 26.09, 18.38, -3.26, -4.67; ESI MS (calcd for
C
23H36O6Si, 436) m/z (relative intensity) 437 (M + H+, 55),
438 (M + H+, 18), 454 (M + NH4+, 100), 455 (M + NH4+, 29),
890 (2M + NH4+, 70), 891 (2M + NH4+, 40). â-10: 1H NMR
(CDCl3, 500 MHz) δ 7.52-7.46 (2H, m), 7.40-7.33 (3H, m),
5.91 (1H, ddt, J ) 17.1, 10.5, 5.4 Hz, H-8), 5.53 (1H, s, H-10),
5.28 (1H, d, J ) 17.5 Hz, H-9a), 5.18 (1H, d, J ) 10.8 Hz, H-9b),
4.74 (1H, s, H-1), 4.38 (1H, dd, J ) 12.7, 5.1 Hz, H-7a), 4.31
(1H, dd, J ) 10.2, 5.1 Hz, H-6eq), 4.05 (1H, dd, J ) 12.7, 6.0
Hz, H-7b), 4.01 (1H, dd, J ) 9.5, 2.2 Hz, H-4), 3.96-3.89 (2H,
m, H-2, H-5), 3.83 (1H, t, J ) 10.15 Hz, H-6ax), 3.65 (1H, t, J
) 2.9 Hz, H-3), 3.55 (3H, s, OCH3), 0.92 (9H, s), 0.12 (3H, s),
0.11 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 137.96, 134.24,
129.11, 128.37, 126.41, 117.15 (C-10), 102.57 (C-10), 98.53
(C-1), 80.10 (C-3), 78.11 (C-4), 71.47, 70.53 (C-7), 69.68 (C-6),
64.03, 60.06 (OCH3), 26.24, 18.69, -4.01, -4.93.
2-O-t er t -Bu t yld im e t h ylsilyl-3-O-m e t h yl-4,6-O-b e n -
zylid en e-r-D-a ltr op yr a n ose (11).14 Anhydrous ZnCl2 (3.70
g, 27.1 mmol) was added to the solution of R- and â-10 (4.70
g, 10.8 mmol) in dry THF (65 mL), and the mixture was stirred
at room temperature for 30 min. Tetrakis(triphenylphosphine)-
palladium(0) (3.12 g, 2.70 mmol) was added, and stirring was
continued for 30 min. Tributyltin hydride (12.5 g, 42.9 mmol)
was added dropwise to the above solution. Upon addition of
Bu3SnH the yellow mixture turned brown. After 1.5 h of
stirring, EtOAc (150 mL) was added, and the organic layer
was washed with 5% HCl (3 × 30 mL) and then dried over
Na2SO4. The solvent was removed under reduced pressure, and
the product 11 (3.55 g, 83% yield) was purified by column flash
chromatography (SiO2, petroleum ether, EtOAc 20%): 1H NMR
(300 MHz, CDCl3) δ 7.52-7.46 and 7.40-7.33 (m), 5.56 (s),
5.51 (s), 5.04-4.95, 4.85-4.79, 4.36-4.24, 4.10-3.97, 3.91-
3.82, 3.80-3.72, 3.71-3.68 (series of m), 3.63 (s), 3.56 (s), 0.96,
0.92, 0.18, 0.17, 0.13, 0.12 (series of s); 13C NMR (75 MHz,
CDCl3) δ 137.71, 129.19, 128.40, 126.36, 126.29, 102.69, 102.58,
96.03, 92.22, 79.84, 79.14, 71.85, 70.22, 69.86, 69.53, 63.28,
60.84, 60.23, 59.27, 26.01, 25.99, 18.34, 13.92, -4.66; ESI MS
(calcd for C20H32O6Si, 396) m/z (relative intensity) 397 (M +
H+, 100), 398 (M + H+, 28), 414 (M + NH4+, 70), 415 (M +
NH4+, 19), 815 (2M + Na+, 38), 816 (2M + Na+, 20).
O-(2-O-ter t-Bu t yld im et h ylsilyl-3-O-m et h yl-4,6-O-b en -
zylid en e-r-D-a ltr op yr a n osyl)tr ich lor oa cetim id a te (r-12)
an d O-(2-O-ter t-Bu tyldim eth ylsilyl-3-O-m eth yl-4,6-O-ben -
zyliden e-â-D-altr opyr an osyl)tr ich lor oacetim idate (â-12).15
To a solution of 11 (400 mg, 1.00 mmol) and trichloroacetoni-
trile (1.0 mL, 10.0 mmol) in dry CH2Cl2 (10 mL) was added
NaH (192 mg, 7.6 mmol), and the resulting mixture was stirred
at room temperature for 6 h. The mixture was slowly poured
into cold water (ca. 30 mL), and the product was extracted
with CH2Cl2 (3 × 30 mL). The organic layer was dried over
Na2SO4, and then the solvent was removed under reduced
pressure. The products R- and â-12 (325 mg, 0.60 mmol, R/ â
≈ 1/4, 60% yield) were isolated by column chromatography
(SiO2, petroleum ether, EtOAc 10%, Et3N 0.5%). R-12: 1H
NMR (500 MHz, CDCl3) δ 8.68 (1H, s, NH), 7.52-7.49 (2H,
m), 7.39-7.34 (3H, m), 6.06 (1H, s, H-1), 5.53 (1H, s, H-8),
4.37(1H, dd, J ) 10.4, 4.9 Hz, H-6eq), 4.15-4.08 (3H, m, H-2,
H-4, H-5), 3.85 (1H, t, J ) 9.8 Hz, H-6ax), 3.74 (1H, dd, J )
3.1, 2.4 Hz, H-3), 3.59 (3H, s, OCH3), 0.95 (9H, s), 0.17 (3H,
s), 0.15 (3H, s); 13C NMR (75 MHz, CDCl3) δ 161.37, 137.69,
129.23, 128.42, 126.41, 102.69 (C-8), 96.00 (C-1), 79.74 (C-3),
77.57, 70.34, 69.39, 64.92, 60.19 (OCH3), 26.10, 18.40, -4.35,
-4.70. â-12: 1H NMR (500 MHz, CDCl3) δ 8.51 (1H, s, NH),
7.53-7.50 (2H, m), 7.38-7.33 (3H, m), 5.94 (1H, s, H-1), 5.60
(1H, s, H-7), 4.50 (1H, dt, J ) 10.4, 5.5 Hz, H-5), 4.34 (1H, dd,
J ) 10.4, 5.5 Hz, H-6eq), 4.24 (1H, d, J ) 3.1 Hz, H-2), 4.10
(1H, dd, J ) 9.8, 3.1 Hz, H-4), 3.77 (1H, t, J ) 10.4 Hz, H-6ax),
3.68 (1H, t, J ) 3.1 Hz, H-3), 3.52 (3H, s, OCH3), 0.95 (9H, s),
Allyl-2-O-a cet yl-3-O-m et h yl-4,6-O-b en zylid en e-r-D-a l-
tr op yr a n osid e (r-9) a n d Allyl-2-O-a cetyl-3-O-m eth yl-4,6-
O-ben zylid en e-â-D-a ltr op yr a n osid e (â-9). Acetic anhydride
(2 equiv) was added to a 0.05 M solution of R-8 or â-8 and
DMAP (0.15 equiv) in EtOAc. The mixture was stirred at room
temperature under nitrogen until TLC indicated completion
of the reaction. Methanol (ca. 150 equiv) was added, and
stirring was continued for 10 min. Saturated aqueous NH4Cl
was added, followed by extraction with EtOAc. The organic
layer was dried over sodium sulfate, and the solvent was
removed under reduced pressure to afford quantitative R-9 or
â-9. R-9: 1H NMR (500 MHz, CDCl3) δ 7.52-7.48 (2H, m),
7.38-7.34 (3H, m), 5.91 (1H, dddd, J ) 17.1, 10.4, 6.1, 4.7 Hz,
H-8), 5.58 (1H, s, H-10), 5.33 (1H, dd, J ) 17.1, 1.3 Hz, H-9a),
5.22 (1H, d, J ) 10.4 Hz, H-9b), 5.14 (1H, d, J ) 2.1 Hz, H-2),
4.73 (1H, s, H-1), 4.38 (1H, ddd, J ) 10.1, 9.8, 5.5 Hz, H-5),
4.32 (1H, dd, J ) 10.1, 5.5 Hz, H-6eq), 4.24 (1H, dd, J ) 13.2,
4.7 Hz, H-7a), 4.05 (1H, dd, J ) 13.2, 6.1 Hz, H-7b), 3.92 (1H,
dd, J ) 9.8, 2.9 Hz, H-4), 3.75 (1H, t, J ) 10.1 Hz, H-6ax),
3.71 (1H, broad s, H-3), 3.58 (3H, s, OCH3), 2.14 (3H, s, OAc);
13C NMR (75 MHz, CDCl3) δ 169.49 (OAc), 137.62, 133.74,
129.17, 128.37, 126.37, 117.72 (C-9), 102.51 (C-10), 97.06
(C-1), 77.40 (C-4), 75.68 (C-3), 70.19 (C-2), 69.46 (C-6), 68.60
(C-7), 59.77 (OCH3), 58.66 (C-5), 21.28 (OAc). â-9: 1H NMR
(500 MHz, CDCl3) δ 7.50-7.47 (2H, m), 7.39-7.34 (3H, m),
5.89 (1H, dddd, J ) 17.1, 11.0, 6.1, 5.8 Hz, H-8), 5.53 (1H, s,
H-10), 5.29 (1H, dd, J ) 17.1, 1.1 Hz, H-9a), 5.22-5.18 (2H,
m, H-2 and H9b), 4.95 (1H, s, H-1), 4.38-4.33 (2H, m, H-7a
and H-6eq), 4.11(1H, dd, J ) 12.8, 6.1 Hz, H-7b), 4.01 (1H, dt,
J ) 9.8, 5.2 Hz, H-5), 3.89 (1H, dd, J ) 9.8, 2.4 Hz, H-4), 3.83
(1H, t, J ) 10.1 Hz, H-6ax), 3.76 (1H, broad t, J ) 2.8 Hz,
H-3), 3.74 (3H, s, OCH3), 2.18 (3H, s, OAc); 13C NMR (75 MHz,
CDCl3) δ 169.94 (OAc), 137.54, 133.62, 129.18, 128.38, 126.28,
117.74 (C-9), 102.48 (C-10), 96.58 (C-1), 77.81 (C-4), 76.59
(C-3), 70.58 (C-7), 70.19 (C-2), 69.29 (C-6), 63.83 (C-5), 60.16
(OCH3), 21.34 (OAc).
Allyl-2-O-ter t-bu tyldim eth ylsilyl-3-O-m eth yl-4,6-O-ben -
zylid en e-r-D-a ltr op yr a n osid e (r-10) a n d Allyl-2-O-ter t-
bu tyld im eth ylsilyl-3-O-m eth yl-4,6-O-ben zylid en e-â-D-a l-
tr op yr a n osid e (â-10). A mixture of R-8 (700 mg, 2.17 mmol)
or â-8 (1.35 g, 4.20 mmol), imidazole (2.2 equiv), and TBDMSCl
(2.2 equiv) in dry DMF (6 mL/mmol of 8) was stirred at room
temperature under nitrogen overnight (16 h). Water (20 mL)
was added, and the mixture was extracted with EtOAc (3 ×
20 mL). The organic layer was dried over sodium sulfate, and
the solvent was removed in vacuo. Column chromatography
(SiO2, petroleum ether, EtOAc 10%) afforded the product R-10
(850 mg, 90% yield) or â-10 (1.73 g, 94% yield) as pale yellow
oils. R-10: 1H NMR (500 MHz, CDCl3) δ 7.53-7.49 (2H, m),
7.39-7.33 (3H, m), 5.91 (1H, dddd, J ) 17.1, 10.4, 6.7, 4.9 Hz,
H-8), 5.57 (1H, s, H-10), 5.32 (1H, dd, J ) 17.1, 1.2 Hz, H-9a),
5.21 (1H, d, J ) 10.4 Hz, H-9b), 4.62 (1H, s, H-1), 4.35-4.26
(2H, m, H-5 and H-6eq), 4.22 (1H, dd, J ) 13.4 Hz, 4.9 Hz,
H-7a), 4.07-3.99 (3H, m, H-2, H-4 and H-7b), 3.75 (1H, t, J )
9.8 Hz, H-6ax), 3.60 (1H, t, J ) 2.4 Hz, H-3), 3.57 3H, s, OCH3),
J . Org. Chem, Vol. 68, No. 21, 2003 8053

Pasetto and Franck
0.17 (3H, s), 0.16 (3H, s); 13C NMR (75 MHz, CDCl3) δ 161.20,
137.70, 129.10, 128.33, 126.47, 102.57, 98.36, 78.14, 76.74,
69.48, 67.97, 61.21, 58.86, 26.04, 18.33, -4.52, -4.698.
ether, EtOAc 10%, Et3N 0.3%) to obtain 16 (1.00 g, 70%
yield): 1H NMR (500 MHz, CDCl3) δ 7.57 (2H, d, J ) 7.3 Hz),
7.53-7.49 (2H, m), 7.40-7.35 (3H, m), 7.30 (2H, t, J ) 7.3
Hz), 7.20 (1H, t, J ) 7.3 Hz), 5.78 (1H, s, H-1), 5.60 (1H, s,
H-8), 4.48 (1H, dd, J ) 10.1, 5.2 Hz, H-7eq), 4.33-4.30 (2H,
m, H-3 and H-5), 4.24 (1H, dt, J ) 10.1, 5.2 Hz, H-6), 3.93
(1H, t, J ) 10.1 Hz, H-7ax), 3.73 (1H, t, J ) 2.7 Hz, H-4), 3.58
(3H, s, OCH3), 0.91 (9H, s, TBDMS), 0.15 (3H, s, TBDMS),
0.09 (3H, s, TBDMS); 13C NMR (75 MHz, CDCl3) δ 151.00
(C-2), 137.66, 135.08, 129.22, 128.95, 128.42, 128.30, 126.90,
126.42, 114.43 (C-1), 102.76 (C-8), 79.49 (C-4), 77.71 (C-3 or
C-5), 73.37 (C-5 or C-3), 69.63 (C-7), 67.13 (C-6), 59.65 (OCH3),
26.08, 18.42, -4.11, -4.54; ESI MS (calcd for C27H36O5Si, 468)
m/z (relative intensity) 469 (M + H+, 100), 470 (M + H+, 47),
954 (2M + NH4+, 49), 955 (2M + NH4+, 29).
(Z)-2,6-An h yd r o-1-d eoxy-1-p h en yl-4-O-m et h yl-5,7-O-
ben zylid en e-D-a ltr o-h ep t-1-en itol (19). To a solution of exo-
glycal 16 (120 mg, 0.26 mmol) dissolved in THF (6 mL) was
added tetrabutylammonium fluoride (1 M in THF, 0.27 mL),
and the mixture was stirred at room temperature for ca. 2 h.
The solvent was removed under reduced pressure, and the
product (70 mg, 76% yield) was purified by column chroma-
tography (SiO2, petroleum ether, EtOAc 30%) as a white
solid: 1H NMR (500 MHz, CDCl3) δ 7.58 (2H, d, J ) 7.3 Hz),
7.52-7.48 (2H, m), 7.40-7.35 (3H, m), 7.30 (2H, t, J ) 7.3
Hz), 7.21 (1H, d, J ) 7.3 Hz), 5.76 (1H, s), 5.61 (1H, s), 4.50
(1H, dd, J ) 10.4, 4.9 Hz, H-7eq), 4.37 (1H, d, J ) 3.7 Hz,
H-3), 4.34 (1H, dd, J ) 9.8, 2.4 Hz, H-5), 4.28 (1H, dt, J )
10.0, 4.9 Hz, H-6), 3.94 (1H, t, J ) 10.4 Hz, H-7ax), 3.86 (1H,
t, J ) 3.1 Hz, H-4), 3.58 (3H, s, OCH3); 13C NMR (75 MHz,
CDCl3) δ 151.23 (C-2), 137.81, 134.88, 129.19, 129.11, 128.39,
127.23, 126.46, 114.68 (C-1), 102.83 (C-8), 78.19 (C-4), 77.45
(C-5), 73.13 (C-3), 69.54 (C-7), 67.24 (C-6), 59.79 (OCH3); ESI
MS (calcd for C21H22O5, 354) m/z (relative intensity) 355 (M +
H+, 100), 356 (M + H+, 31), 377 (M + Na+, 59), 378 (M + Na+,
20), 731 (2M + Na+, 19), 732 (2M + Na+, 9).
(1R )-2,6-An h y d r o -1-p h e n y l-4-O -m e t h y l-5,7-O -b e n -
zylid en e-r-D-a ltr o-h ep titol (20) a n d (1S)-2,6-An h yd r o-1-
p h en yl-4-O-m eth yl-5,7-O-ben zylid en e-â-D-a ltr o-h ep titol
(21).17 To a solution of the exo-glycal 19 (400 mg, 1.13 mmol)
in dry THF (12 mL) was added borane (1 M in THF, 1.3 mL)
at 0 °C (ice bath) under nitrogen. The mixture was stirred at
low temperature for 1 h and then at room temperature for an
additional 2 h. The reaction was monitored by taking a small
aliquot (ca. 0.05 mL) of the reaction mixture and checking the
TLC after basic oxidative workup. The reaction mixture was
cooled at 0 °C, and KOH (5% in water, 2 mL) and H2O2 (30%,
2 mL) were added dropwise. The mixture was stirred for 30
min at room temperature, water (12 mL) was added, and then
an extraction with EtOAc (3 × 20 mL) was performed. The
organic layer was dried over sodium sulfate, and the two
products 20 (30 mg, 0.08 mmol, 7%) and 21 (270 mg, 0.72
mmol, 64%) were separated by column chromatography (SiO2,
petroleum ether, EtOAc 30%). Alternatively, the hydroboration
was conducted on the exo-glycal 16 (100 mg, 0.21 mmol), which
was treated with borane (1 M in THF, 0.4 mL) in THF (5 mL)
under the same conditions described above. After basic oxida-
tive workup and column chromatography (petroleum ether,
EtOAc 10%) an inseparable mixture of the 17 and 18 (80 mg)
was obtained. An aliquot (32 mg) of this product was treated
with TBAF (1 M in THF, 0.07 mL) in THF (3 mL) for 1 h at
room temperature. By comparison of the 1H NMR spectrum
of the reaction crude with the spectra of 20 and 21, it was
possible to calculate the ratio R/â ) 1/10. 20: Rf 0.24 (PE/
EtOAc, 4/6); 1H NMR (500 MHz, CDCl3) δ 7.51-7.48 (2H, m),
7.40-7.35 and 7.30-7.29 (8H, m), 5.54 (1H, s, H-8), 5.37 (1H,
d, J ) 8.5 Hz, H-1), 4.46 (1H, d, J ) 3.1 Hz, H-3), 4.32 (1H,
dt, J ) 9.8, 5.5 Hz, H-6), 4.12 (1H, dd, J ) 9.8, 5.5 Hz, H-7eq),
4.08 (1H, dd, J ) 9.8, 2.4 Hz, H -5), 3.88 (1H, d, J ) 8.5 Hz,
H-2), 3.85 (1H, t, J ) 3.1 Hz, H-4), 3.68 (3H, s, OCH3), 3.59
(1H, t, J ) 9.8 Hz, H-7ax); 13C NMR (75 MHz, CDCl3) δ 142.46,
137.94, 129.08, 128.64, 128.33, 128.02, 126.50, 126.36, 102.61
Ben zyl-2-O-ter t-bu tyld im eth ylsilyl-3-O-m eth yl-1-th io-
r,â-D-a ltr op yr a n osid e (13). To a solution of 12 (280 mg, 0.52
mmol) and benzyl mercaptan (106 mg, 0.85 mmol) in dry
CH2Cl2 (106 mg, 0.85 mmol) cooled at -78 °C was added
dropwise BF3‚OEt2 (6 mg, 0.04 mmol). The mixture was stirred
at -78 °C for 40 min and then at room temperature for 20
min. A saturated solution of NaHCO3 (15 mL) was added, and
the product was extracted with EtOAc (3 × 25 mL). The
product 13 was isolated as a 2/1 ratio of anomers in 95% yield
by column chromatography (SiO2, petroleum ether, EtOAc
50%): 1H NMR (CDCl3, 500 MHz) δ 7.34-7.30 (5H, m), 4.80
(1H, s), 4.04-4.02, 3.93-3.91, 3.89-3.83, 3.80-3.75, 3.74-
3.68, 3.45-3.37 (series of m), 3.47 (3H, s), 3.41 (3H, s), 0.92
(9H, s), 0.81 (9H, s), 0.16 (3H, s), 0.11 (3H, s), -0.04 (3H, s),
-0.10 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 138.46, 138.33,
129.20, 129.05, 128.63, 127.18, 127.14, 83.99, 81.73, 81.54,
80.48, 77.31, 70.52, 69.77, 65.41, 65.33, 63.57, 63.28, 58.94.
58.61, 36.46, 35.94, 26.09, 25.92, 18.42, 18.25, -4.27, -4.41,
-4.79, -4.88.
Ben zyl-2-O-ter t-b u t yld im et h ylsilyl-3-O-m et h yl-4,6-O-
ben zylid en e-1-th io-r,â-D-a ltr op yr a n osid e (14). A solution
of 13 (1.35 g, 3.26 mmol), benzaldehyde dimethyl acetal (1.48
g, 9.72 mmol), and p-toluenesulfonic acid (60 mg, 0.32 mmol)
dissolved in acetonitrile (40 mL) was stirred at room temper-
ature for 9 h. Acidic resin was added, and the mixture was
filtered. The solvent was removed under reduced pressure to
obtain the product 14 in 98% yield. The product consisted of a
mixture of R- and â-anomers, but it was not possible to assign
the NMR peaks corresponding to each anomer: 1H NMR
(CDCl3, 500 MHz, major anomer) δ 7.51-7.48(2H, m), 7.38-
7.33, 7.33-7.29, 7.27-7.23 (8H, series of m), 5.52 (1H, s), 4.78
(1H, s, H-1), 4.27 (1H, dd, J ) 10.4, 4.9 Hz, H-6eq), 4.00 (1H,
dd, J ) 9.8, 2.4 Hz, H-4), 3.92-3.86 (3H, m, H-2, H-5, H-7),
3.81 (1H, t, J ) 10.4 Hz, H-6ax), 3.56 (1H, t, J ) 2.4 Hz, H-3),
3.48 (3H, s), 0.94 (9H, s), 0.16 (3H, s), 0.12 (3H, s); 13C NMR
(CDCl3, 75 MHz, major anomer) δ 138.19, 137.82, 129.14,
128.67, 128.41, 127.20, 126.40, 102.58, 82.35, 79.38, 77.71,
73.13, 69.52, 66.79, 59.89, 35.70, 26.23, 26.15, 18.49, -4.32,
-4.42.
O-ter t-Bu tyldim eth ylsilyl-3-O-m eth yl-4,6-O-ben zyliden e-
1-su lfon yl-r,â-D-a ltr op yr a n osid e (15). The thioglucoside 14
(150 mg, 0.30 mmol) was dissolved in THF (8 mL), ethanol (8
mL), and water (7 mL). Magnesium monoperoxyphthalate
hexahydrate (MMPP, 80%, 500 mg, 0.81 mmol) was added,
and the mixture was stirred for 3 h at ∼65 °C. The solvent
was partially evaporated. Water was added, and the product
was extracted with dichloromethane. The organic layer was
washed with a saturated solution of NaHCO3 and then dried
over sodium sulfate. The solvent was removed under reduced
pressure to obtain the sulfone 15 (145 mg, 90% yield): 1H NMR
(300 MHz, CDCl3) δ 7.52-7.48 and 7.42-7.34 (m), 5.552 (1H,
s), 5.546 (1H, s), 4.63 (d, J ) 1.1 Hz), 4.58 (1H, J ) 3.3 Hz),
4.50-4.47, 4.46-4.43, 4.41-4.34, 4.23-4.20, 4.17-4.15, 4.14-
4.08, 4.04-3.97, 3.69-3.65 (series of m), 3.54 (3H, s), 3.51 (3H,
s), 0.97 (9H, s), 0.77 (9H, s), 0.20 (3H, s), 0.07 (3H, s), -0.05
(3H, s), -0.23 (3H, s); ESI MS (calcd for C27H38O7SSi, 534)
m/z (relative intensity) 535 (M + H+, 51), 552 (M + NH4+, 100),
553 (M + NH4+, 37).
(Z)-2,6-An h yd r o-1-d e oxy-1-p h e n yl-3-O-t er t -b u t yld i-
m et h ylsilyl-4-O-m et h yl-5,7-O-b en zylid en e-D-a lt r o-h ep t -
1-en itol (16).9 The sulfone 15 (1.10 g, 2.06 mmol) was
dissolved in dichloromethane (10 mL) and tert-butyl alcohol
(10 mL). The mixture was cooled in an ice bath and 30% KOH
on alumina (3.0 g) was added, followed by dibromodifluo-
romethane (ca. 5 mL, 55 mmol). The mixture was stirred at 0
°C for 1 h and at room temperature for 3 h. The mixture was
filtered through Celite, the filtrate was collected and the
solvent was removed under reduced pressure. The crude was
purified by flash column chromatography (SiO2, petroleum
8054 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
(C-8), 83.12 (C-2 or C-4), 78.53 (C-4 or C-2), 77.80 (C-5), 72.43
6.85 (2H, d, J ) 8.5 Hz), 5.60 (1H, s, H-1), 5.56 (1H, s, H-8),
4.66 (1H, d, J ) 11.6 Hz, PMB), 4.65 (1H, d, J ) 11.6 Hz,
PMB), 4.60 (1H, d, J ) 11.6 Hz, PMB), 4.57 (1H, dd, J ) 10.4,
5.5 Hz, H-7eq), 4.45 (1H, d, J ) 11.6 Hz, PMB), 4.34 (1H, dt,
J ) 9.8, 5.5 Hz, H-6), 3.99 (1H, d, J ) 2.4 Hz, H-3), 3.94 (1H,
dd, J ) 7.3, 2.4 Hz, H-4), 3.90-3.84 (2H, m, H-5 and H-7a),
3.82 (3H, s, PMB), 3.79 (3H, s, PMB);
CDCl3) δ 159.44, 159.37, 147.89, 137.40, 135.12, 130.28, 129.97,
129.56, 129.52, 129.09, 128.74, 128.34, 128.29, 126.58, 126.30,
114.04, 113.94, 110.16 (C-1), 101.54 (C-8), 82.14 (C-5), 81.18
(C-4), 80.17 (C-3), 72.41, 70.29, 69.56 (C-7), 66.32 (C-6), 55.45;
ESI MS (calcd for C36H36O7, 580) m/z (relative intensity) 598
(M + NH4+, 100), 599 (M + NH4+, 37).
(C-1), 69.87 (C-7), 68.12 (C-3), 62.38 (C-6), 60.36 (OCH3). 21:
1
Rf 0.39 (PE/EtOAc, 4/6); H NMR (500 MHz, CDCl3) δ 7.50-
7.47 (2H, m), 7.45-7.32 (8H, m), 5.56 (1H, s, H-8), 5.20 (1H,
t, J ) 3.1 Hz, H-1), 4.33 (1H, dd, J ) 10.4, 4.9 Hz, H-7eq),
4.15 (1H, dd, J ) 9.8, 2.4 Hz, H-5), 4.05 (1H, dt, J ) 9.8, 4.9
Hz, H-6), 4.00 (1H, broad s, OH), 3.88 (1H, d, J ) 3.1 Hz, H-2),
3.84 (1H, broad d, J ) 3.1 Hz, H-3), 3.81 (1H, t, J ) 10.4 Hz,
H-7ax), 3.62 (1H, t, J ) 3.1 Hz, H-4), 3.42 (3H, s, OCH3), 2.86
(1H, d, J ) 3.1 Hz); 13C NMR (75 MHz, CDCl3) δ 139.15,
138.10, 129.05, 128.82, 128.34, 128.19, 126.41, 125.92, 102.64
(C-8), 78.44 (C-5), 77.62 (C-4), 77.38 (C-2), 76.15 (C-1), 69.69
(C-7), 69.27 (C-2), 67.36 (C-6), 59.83 (OCH3); ESI MS (calcd
for C21H24O6, 372) m/z (relative intensity) 395 (M + Na+, 100),
396 (M + Na+, 23), 767 (2M + Na+, 42), 768 (2M + Na+, 22).
13C NMR (75 MHz,
(1R)-2,6-An h ydr o-1-ph en yl-3,4-bis-O-(4-m eth oxyben zyl)-
5,7-O-ben zylid en e-r-D-glu co-h ep titol (32) a n d (1S)-2,6-
An h ydr o-1-ph en yl-3,4-bis-O-(4-m eth oxyben zyl)-5,7-O-ben -
zylid en e-â-D-glu co-h ep t it ol (33).17 By following the same
procedure described for the preparation of 17 and 18, hydrobo-
ration of 31 (1.0 g, 1.7 mmol) afforded the two products 32
(533 mg, 0.89 mmol, 53%) and 33 (180 mg, 0.30 mmol, 18%),
which were separated by column chromatography (SiO2,
petroleum ether, EtOAc 10%). 32: Rf 0.30 (petroleum ether,
EtOAc 30%); 1H NMR (500 MHz, CDCl3) δ 7.51-7.47 (2H, m),
7.41-7.25 (12H, m), 6.91-9.85 (4H, m), 5.51 (1H, s, H-8), 5.11
(1H, dd, J ) 8.5, 2.4 Hz, H-1), 4.86 (1H, d, J ) 11.0 Hz), 4.79
(1H, d, J ) 11.0 Hz), 4.74 (1H, d, J ) 11.0 Hz), 4.57 (1H, d, J
) 11.0 Hz), 4.07 (1H, t, J ) 7.6 Hz, H-4), 4.02 (1H, dd, J )
8.5, 4.9 Hz, H-2), 3.99-3.92 (2H, m, H-3 and H-7eq), 3.90 (1H,
d, J ) 2.4 Hz, OH), 3.811 (3H, s, OCH3), 3.806 (3H, s, OCH3),
3.74-3.70 (2H, m, H-5 and H-6), 3.48-3.44 (1H, m, H-7ax);
13C NMR (75 MHz, CDCl3) δ 159.86, 159.49, 140.82, 137.52,
130.57, 130.08, 129.74, 129.31, 129.04, 128.46, 128.34, 128.02,
126.98, 126.14, 114.27, 114.02, 101.31 (C-8), 82.73 (C-5 or C-6),
79.65 (C-3), 78.79 (C-4), 76.75 (C-2), 74.21, 74.02, 73.38 (C-1),
69.56 (C-7), 65.28 (C-6 or C-5), 55.52; ESI MS (calcd for
Ben zyl-2,3-bis-O-(4-m eth oxyben zyl)-4,6-O-ben zyliden e-
1-th io-â-D-glu cop yr a n osid e (29). The thioglucoside 28 (14.80
g, 39.5 mmol) dissolved in DMF (75 mL) and THF (40 mL)
was added dropwise at 0 °C (ice bath) to a suspension of NaH
(0.107 mol, 60% dispersion in mineral oil, washed free of oil
with pentane) in DMF (25 mL) and THF (15 mL), followed by
addition of PMBCl (0.10 mol) and tetrabutylammonium iodide
(7.9 mmol). The mixture was stirred at low temperature for
30 min and then at room temperature overnight (10 h).
Methanol (8 mL) was added dropwise. The mixture was stirred
for 1 h, and then the solvent was partially removed under
reduced pressure. Saturated aqueous NH4Cl (100 mL) was
added, and the product was extracted with EtOAc (3 × 100
mL). The organic layer was dried over sodium sulfate, and the
solvent was removed. The crude was dissolved in EtOAc (ca.
70 mL), and such solution was poured in an Erlenmeyer flask
containing petroleum ether (ca. 700 mL). The flask was stored
in a freezer for 1 h, and then the white crystals formed were
filtered and washed with cold petroleum ether (ca. 100 mL) to
obtain 20.88 g (86% yield) of 29: 1H NMR (300 MHz, CDCl3)
δ 7.50-7.44 (2H, m), 7.38-7.21 (12H, m), 6.86-6.78 (4H, m),
5.54 (1H, s), 4.83 (1H, d, J ) 11.0 Hz), 4.75-4.65 (3H, m),
4.38 (1H, d, J ) 9.9 Hz), 4.30 (1H, dd, J ) 10.6, 4.9 Hz), 3.95
(1H, d, J ) 13.2 Hz), 3.86 (1H, d, J ) 13.2 Hz), 3.76 (3H, s),
3.74 (3H, s), 3.77-3.61 (3H, m), 3.44 (1H, t, J ) 9.1 Hz), 3.33
(1H, m); 13C NMR (75 MHz, CDCl3) δ 159.39, 159.27, 137.55,
137.40, 130.71, 130.27, 129.92, 129.69, 129.04, 128.95, 128.61,
128.24, 127.27, 126.06, 113.83, 101.21, 84.76, 82.57, 81.74,
81.00, 75.51, 74.93, 70.31, 68.81, 55.41, 55.38, 35.00; ESI MS
(calcd for C36H38O7S, 614) m/z (relative intensity) 632 (M +
NH4+, 100), 633 (M + NH4+, 36).
Ben zyl-2,3-bis-O-(4-m eth oxyben zyl)-4,6-O-ben zyliden e-
1-su lfon yl-â-D-glu cop yr a n osid e (30). The sulfone 30 (11.0
g, 95% yield) was prepared from 29 (11.0 g, 17.9 mmol) by
following the same procedure described for 15: 1H NMR (300
MHz, CDCl3) δ 7.48-7.44 (2H, m), 7.40-7.34 (8H, m), 7.30-
7.23 (4H, m), 6.85-6.81 (4H, m), 5.58 (1H, s, H-7), 4.85 (1H,
d, J ) 11.0 Hz, PMB), 4.81 (1H, d, J ) 9.8 Hz, PMB), 4.77
(1H, d, J ) 9.8 Hz, PMB), 4.72 (1H, d, J ) 11.0 Hz, PMB),
4.44-4.39 (2H, m, H-6eq and H-1′a), 4.27-4.21 (2H, m, H-1
and H-1′b), 4.11 (1H, t, J ) 9.2 Hz, H-2), 3.87 (1H, t, J ) 9.8
Hz, H-6ax), 3.82-3.71 (8H, m, H-3, H-4 and PMB), 3.39 (1H,
dt, J ) 9.8, 4.9 Hz, H-5); 13C NMR (75 MHz, CDCl3) δ 159.45,
159.36, 136.99, 131.00, 130.31, 129.71, 129.13, 129.06, 128.96,
128.29, 127.19, 126.04, 113.91, 113.86, 101.40, 88.00 (C-1),
82.14, 80.80, 76.41 (C-2), 75.51, 75.00, 70.80 (C-5), 68.34
C
36H38O8, 598) m/z (relative intensity) 616 (M + NH4+, 100),
617 (M + NH4+, 38). 33: Rf 0.18 (petroleum ether, EtOAc 30%);
1H NMR (500 MHz, CDCl3) δ 7.50-7.47 (2H, m), 7.39-7.27
(8H, m), 7.22 (2H, d, J ) 8.5 Hz), 7.15 (2H, d, J ) 8.5 Hz),
6.87 (2H, d, J ) 8.5 Hz), 6.82 (2H, d, J ) 8.5 Hz), 5.54 (1H, s,
H-8), 4.92-4.86 (3H, m, H-1 and PMB), 4.67 (1H, d, J ) 11.0
Hz, PMB), 4.43 (1H, d, J ) 10.4 Hz, PMB), 4.34 (1H, dd, J )
10.4, 4.9 Hz, H-7eq), 3.88 (1H, t, J ) 9.2 Hz, H-4), 3.83-3.78
(4H, m, H-2 and OCH3 at 3.80 ppm), 3.77 (3H, s, OCH3), 3.69
(1H, t, J ) 9.8 Hz, H-7ax), 3.54 (1H, t, J ) 9.2 Hz, H-5), 3.45
(1H, td, J ) 9.8, 4.9 Hz, H-6), 3.35 (1H, t, J ) 9.2 Hz, H-3),
3.12 (1H, d, J ) 5.5 Hz, OH); 13C NMR (75 MHz, CDCl3) δ
159.40, 159.38, 140.01, 137.50, 130.61, 130.34, 129.84, 129.39,
128.99, 128.29, 128.15, 127.94, 127.90, 126.08, 114.03, 113.98,
101.29 (C-8), 83.45 (C-4), 82.53 (C-5), 81.89 (C-2), 78.97 (C-3),
74.71, 74.54 (C-1), 74.22, 70.35 (C-6), 68.97 (C-7), 55.47, 55.42;
ESI MS (calcd for C36H38O8, 598) m/z (relative intensity) 616
(M + NH4+, 100), 617 (M + NH4+, 37).
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
et h oxym et h yl]-3,4-b is-O-(4-m et h oxyb en zyl)-5,7-O-b en -
zylid en e-r-D-glu co-h ep titol (34).25 The C-glucoside 32 (1.07
g, 1.79 mmol) was dissolved in dry methylene chloride (4 mL),
in the presence of diisopropylethylamine (1.05 g, 8.1 mmol).
To this solution SEMCl (0.9 g, 8.1 mmol) was added and the
mixture was stirred at room temperature under nitrogen
atmosphere for ca. 10 h. Methylene chloride (15 mL) was added
and the organic layer was washed with saturated aqueous
NH4Cl (2 × 10 mL). The organic layer was dried over sodium
sulfate and the solvent removed under reduced pressure.
Column chromatography (SiO2, EtOAc 10%, petroleum ether)
afforded 1.29 g (98% yield) of the product 34: 1H NMR (500
MHz, CDCl3) δ 7.48 (2H, m), 7.39-7.26 (12H, m), 6.89-6.86
(4H, m), 5.45 (1H, s, H-8), 4.78 (1H, d, J ) 8.5 Hz, H-1), 4.74
(1H, d, J ) 11.6 Hz, 1/2 AB system, SEM), 4.72 (1H, d, J )
11.6 Hz, 1/2 AB system, SEM), 4.61-4.57 and 4.54-4.49 (4H,
m, PMB), 4.19 (1H, dd, J ) 8.5, 3.1 Hz, H-2), 4.05 (1H, t, J )
3.1 Hz, H-3), 3.97-9.92 (2H, m, H-4 and H-7), 3.83-3.79 (7H,
(C-6), 57.99 (C-7), 55.39; ESI MS (calcd for C36H38O9S, 646)
+
m/z (relative intensity) 664 (M + NH4+, 100), 665 (M + NH4
42).
,
(Z)-2,6-An h yd r o-1-d eoxy-1-p h en yl-3,4-b is-O-(4-m et h -
oxyben zyl)-5,7-O-ben zylid en e-D-glu co-h ep t-1-en itol (31).9
The sulfone 30 (2.70 g, 4.17 mmol) was converted to the exo-
glucal 31 in 70% yield by using the same reaction conditions
as described for the preparation of 16: 1H NMR (500 MHz,
CDCl3) δ 7.58 (2H, d, J ) 7.3 Hz), 7.49 (2H, dd, J ) 7.3, 1.2
Hz), 7.41-7.35 (m, 3H), 7.32 (2H, t, J ) 7.3 Hz), 7.28-7.23
(4H, m), 7.20 (1H, t, J ) 7.3 Hz), 6.89 (2H, d, J ) 8.5 Hz),
J . Org. Chem, Vol. 68, No. 21, 2003 8055

Pasetto and Franck
m, H-5 and 2 OCH3 at 3.81 ppm), 3.74 (1H, td, J ) 10.3, 4.9
Hz, H-6), 3.47 (1H, ddd, J ) 11.6, 9.8, 5.5 Hz, SEM), 3.39 (1H,
t, J ) 10.3 Hz, H-7), 3.30 (1H, ddd, J ) 11.6, 9.8, 5.5 Hz, SEM),
0.73 (1H, ddd, J ) 13.4, 11.6, 5.5 Hz, SEM), 0.57 (1H, ddd, J
) 13.4, 11.6, 5.5 Hz, SEM), -0.11 (9H, s, SEM); 13C NMR (75
MHz, CDCl3) δ 159.30, 139.74, 137.65, 130.50, 130.22, 129.50,
129.43, 128.79, 128.25, 128.12, 127.97, 127.61, 126.09, 113.85,
100.97, 93.72, 82.19 (C-5), 78.46 (C-3), 77.81 (C-1), 77.68
(C-4), 75.82 (C-2), 72.58, 71.99, 69.84 (C-7), 65.79, 64.11
and H-7eq), 3.76 (1H, ddd, J ) 11.6, 9.2, 5.5 Hz, SEM), 3.74
(1H, m, H-3, partially overlapped with ddd at 3.76 ppm), 3.62
(1H, d, J ) 4.9 Hz, H-4), 3.52-3.43 (2H, m, H-7ax and SEM),
0.92 (1H, ddd, J ) 13.4, 11.6, 5.5 Hz), 0.78 (1H, ddd, J ) 13.4,
11.6, 5.5 Hz), -0.03 (9H, s); 13C NMR (75 MHz, CDCl3) δ
139.38, 137.40, 129.25, 128.42, 128.38, 128.16, 127.73, 126.41,
102.76, 93.06, 78.35, 75.79 (C-1), 74.08 (C-2), 69.21 (C-7), 65.67,
62.40, 54.15 (C-3), 51.90 (C-4), 18.13, -1.14; ESI MS (calcd
+
for C26H38O6Si, 470) m/z (relative intensity) 488 (M + NH4
,
(C-6), 55.34, 18.05, -1.25; ESI MS (calcd for C42H56O9Si, 728)
100), 489 (M + NH4+, 36), 958 (2M + NH4+, 13), 963 (2M +
m/z (relative intensity) 746 (M + NH4+, 100), 747 (M + NH4
,
Na+, 9).
+
51), 751 (M + Na+, 35), 752 (M + Na+, 19).
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
et h oxym et h yl]-4-O-m et h yl-5,7-O-b en zylid en e-r-D-a lt r o-
h ep titol (38). The epoxide 36 (1.0 g, 2.1 mmol) was dissolved
in a solution of sodium methoxide in methanol (ca. 2 M, 16
mL) in a pressure tube. The tube was sealed, and the mixture
was stirred at ca. 120 °C (oil bath) for 20 h. The solution was
allowed to cool to room temperature, and then acidic resin was
added until neutral pH was obtained (monitored by pH paper).
The resin was filtered off, and the solvent was removed under
reduced pressure to obtain a quantitative yield (1.0 g) of the
C-altroside 38: 1H NMR (500 MHz, CDCl3) δ 7.50-7.46 (2H,
m), 7.41-7.28 (8H, m), 5.51 (1H, s, H-8), 5.33 (1H, d, J ) 10.4
Hz, H-1), 4.65 (1H, d, J ) 6.1 Hz, SEM), 4.56 (1H, d, J ) 6.1
Hz, SEM), 4.47 (1H, t, J ) 4.0 Hz, H-3), 4.08 (1H, dt, J ) 9.8,
5.5 Hz, H-6), 4.03 (1H, dd, J ) 9.8, 4.0 Hz, H-7eq), 3.87-3.84
(2H, m, H-2 and H-4), 3.65 (3H, s, OCH3), 3.56 (1H, ddd, J )
11.6, 9.2, 6.0 Hz, SEM), 3.49 (1H, t, J ) 10.4 Hz, H-7ax), 3.38
(1H, ddd, J ) 11.6, 9.2, 6.0 Hz, SEM), 1.92 (1H, d, J ) 5.5 Hz,
OH), 0.80 (1H, ddd, J ) 13.4, 11.6, 5.5 Hz, SEM), 0.66 (1H,
ddd, J ) 13.4, 11.6, 5.5 Hz, SEM), -0.04 (9H, s, SEM); 13C
NMR (75 MHz, CDCl3) δ 139.98, 137.88, 129.11, 128.47,
128.38, 128.10, 127.71, 126.31, 102.47 (SEM, OCH2O), 93.59,
81.92, 78.84, 77.88 (C-5), 75.84 (C-1), 69.61 (C-7), 68.89 (C-3),
65.81, 61.85 (C-6), 60.57, 18.16, -1.11; ESI MS (calcd for
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
eth oxym eth yl]-5,7-O-ben zyliden e-r-D-glu co-h eptitol (35).26
To the C-glucoside 34 (1.13 g, 1.55 mmol) dissolved in
methylene chloride (15 mL) and water (7 mL) was added 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ, 1.0 g, 4.4 mmol).
The mixture was stirred vigorously for ca. 1.5 h at room
temperature. A saturated solution of sodium bicarbonate in
water (15 mL) was added dropwise, and the product was
extracted with methylene chloride (4 × 15 mL). The organic
layer was dried over sodium sulfate, and the solvent was
removed in vacuo. Column chromatography (SiO2, EtOAc 15%,
petroleum ether) yielded the product 35 (644 mg, 1.32 mmol,
85%): 1H NMR (500 MHz, CDCl3) δ 7.52-7.48 (2H, m), 7.40-
7.33 (8H, m), 5.50 (1H, s, H-8), 5.25 (1H, d, J ) 8.5 Hz, H-1),
4.64 (1H, d, J ) 6.7 Hz, SEM), 4.50 (1H, d, J ) 6.7 Hz, SEM),
4.29 (1H, d, J ) 6.1 Hz, OH), 4.26 (1H, dd, J ) 8.5, 4.9 Hz,
H-2), 4.11 (1H, t, J ) 9.2 Hz, H-4), 3.98 (1H, ddd, J ) 8.5, 6.1,
4.9 Hz, H-3), 3.94 (1H, dd, J ) 10.4, 4.9 Hz, H-7), 3.78-3.71
(2H, m, H-6 and SEM), 3.58 (1H, t, J ) 9.2 Hz, H-5), 3.54-
3.45 (2H, m, H-7 and SEM), 2.73 (1H, bs, OH), 0.94-0.83 (2H,
m, SEM), 0.01 (9H, s, SEM); 13C NMR (75 MHz, CDCl3) δ
137.64, 137.26, 129.22, 128.79, 128.37, 127.75, 126.40, 101.95
(C-8), 92.76, 82.08 (C-5), 77.54 (C-1), 76.25 (C-2), 74.18 (C-3),
72.99 (C-4), 69.41 (C-7), 66.78, 65.72 (C-6), 18.38, -1.11; ESI
MS (calcd for C26H40O7Si, 488) m/z (relative intensity) 506 (M
+ NH4+, 100), 507 (M + NH4+, 33), 994 (2M + NH4+, 28), 995
(2M + NH4+, 22).
C
27H42O7Si, 502) m/z (relative intensity) 520 (M + NH4+, 100),
521 (M + NH4+, 35).
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
eth oxym eth yl]-4-O-m eth yl-r-D-altr o-h eptitol (39) an d (1R)-
2,6-An h yd r o-1-p h en yl-4-O-m eth yl-r-D-a ltr o-h ep titol (40).
To the benzylidene-protected C-glycoside 38 (1.0 g, 2.0 mmol)
dissolved in methanol (50 mL) was added p-toluensulfonic acid
monohydrate (200 mg, 1.05 mmol), and the mixture was stirred
at room temperature. When the consumption of all of the
starting material was detected by TLC, the reaction was
quenched by addition of triethylamine (3 mL). The solvent was
removed under reduced pressure, and the two products 39
(white solid, 705 mg, 1.7 mmol, 85%) and 40 (oil, 85 mg, 0.3
mmol, 15%) were separated by column chromatography (SiO2,
methanol 3%, EtOAc). Longer reaction time afforded 40 in
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
eth oxym eth yl]-3,4-an h ydr o-5,7-O-ben zyliden e-r-D-m an n o-
h ep titol (36) a n d (1R)-2,6-An h yd r o-1-p h en yl-1-O-[2-(tr i-
m eth ylsilyl)eth oxym eth yl]-3,4-an h ydr o-5,7-O-ben zyliden e-
r-D-a llo-h ep titol (37).12 Sodium hydride (60% in mineral oil,
175 mg, 4.4 mmol) was washed free of oil with pentane. The
C-glucoside 35 (990 mg, 2.03 mmol), dissolved in dry DMF (30
mL), was added dropwise at 0 °C (ice bath), under nitrogen.
The mixture was stirred at 0 °C for 15 min under N2, then a
solution of N-tosylimidazole (511 mg, 2.30 mmol) in DMF (10
mL) was added dropwise, and the mixture was stirred for 15
min at 0 °C and then at room temperature for 1 h. Saturated
aqueous NH4Cl (40 mL) was added, and the product was
extracted with EtOAc (4 × 40 mL). The organic layer was dried
over sodium sulfate, the solvent was removed in vacuo, and
the products 36 (740 mg, 1.57 mmol, 77%) and 37 (190 mg,
0.40 mmol, 20%) were isolated by column chromatography
(SiO2, EtOAc 5 to 10%, petroleum ether). 36: Rf 0.4 (PE/EtOAc,
quantitative yield. 39: [R]25 ) -57.0 (c ) 2.85, CH2Cl2); mp
D
64-67 °C. Anal. Calcd for C20H34O7Si: C, 57.94; H, 8.27.
Found: C, 57.93; H, 8.25; 1H NMR (500 MHz, CDCl3) δ 7.40-
7.29 (5H, m), 4.91 (1H, d, J ) 8.5 Hz, H-1), 4.64 (1H, d, J )
6.7 Hz, SEM), 4.55 (1H, d, J ) 6.7 Hz, SEM), 4.10 (1H, dt, J
) 7.0, 2.4 Hz, H-3), 3.89-3.84 (2H, m, H-5 and H-6), 3.72-
3.65 (2H, m, H-2 and SEM), 3.63-3.57 (1H, m, H-7a), 3.56
(3H, s, OCH3), 3.50-3.41 (3H, m, H-4, H-7b, SEM), 3.35 (1H,
d, J ) 2.4 Hz, OH-3), 2.54 (1H, d, J ) 4.3 Hz, OH-5), 1.32
1
8/2); H NMR (500 MHz, CDCl3) δ 7.53-7.49 (2H, m), 7.42-
7.31 (8H, m), 5.55 (1H, s, H-8), 5.03 (1H, d, J ) 7.3 Hz, H-1),
4.69 (1H, d, J ) 6.7 Hz, SEM), 4.61 (1H, d, J ) 6.7 Hz, SEM),
4.22 (1H, d, J ) 7.3 Hz, H-2), 4.07-4.01 (1H, m, H-7), 3.74
(1H, td, J ) 9.8, 6.7 Hz, SEM), 3.63-3.49 (6H, m), 0.93-0.82
(1H, m), 0.01 (9H, s); 13C NMR (75 MHz, CDCl3) δ 138.18,
137.31, 129.25, 128.73, 128.41, 127.46, 126.25, 102.35 (C-8),
93.06, 77.92 (C-1), 76.06, 75.97, 69.79 (C-7), 66.25, 65.47, 54.68,
50.37, 18.36, -1.08; ESI MS (calcd for C26H38O6Si, 470) m/z
(relative intensity) 488 (M + NH4+, 100), 489 (M + NH4+, 34),
963 (2M + Na+, 8). 37: Rf 0.3 (PE/EtOAc, 8/2); 1H NMR (500
MHz, CDCl3) δ 7.52-7.49 (2H, m), 7.40-7.33 and 7.32-7.28
(8H, m), 5.53 (1H, s, H-8), 4.99 (1H, d, J ) 9.2 Hz, H-1), 4.72
(1H, d, J ) 6.7 Hz, SEM), 4.61 (1H, d, J ) 6.7 Hz, SEM), 4.11
(1H, dd, J ) 9.2, 3.1 Hz, H-2), 4.01-3.93 (3H, m, H-5, H-6
(1H, OH-7), 0.89-0.75 (2H, m, SEM), -0.01 (9H, s, SEM); 13
C
NMR (75 MHz, CDCl3) δ 138.81, 128.54, 128.02, 93.08 (SEM,
OCH2O), 81.62 (C-4), 79.42 (C-1), 76.93 (C-2), 75.95 (C-5 or
C-6), 69.34 (C-3), 66.27 (SEM, OCH2CH2SiMe3), 65.67 (C-5 or
C-6), 60.64 (C-7), 58.61 (OCH3), 18.32 (SEM, OCH2CH2SiMe3),
-1.09 (SEM, Si(CH3)3); ESI MS (calcd for C20H38O7Si, 414) m/z
(relative intensity) 432 (M + NH4+, 100), 433 (M + NH4+, 33),
851 (2M + Na+, 16). 40: 1H NMR (500 MHz, CDCl3) δ 7.44
(2H, d, J ) 7.6 Hz), 7.37 (2H, t, J ) 7.6 Hz), 7.32 (1H, t, J )
7.6 Hz), 4.96 (1H, d, J ) 7.6 Hz, H-1), 4.14 (1H, t, J ) 7.6 Hz),
3.98 (1H, ddd, J ) 8.9, 4.4, 3.2 Hz, H-6), 3.94 (1H, t, J ) 3.2
Hz, H-5), 3.69 (1H, dd, J ) 11.4, 8.9 Hz, H-7a), 3.64 (1H, t, J
) 7.6 Hz, H-2), 3.54 (3H, s, OCH3), 3.51 (1H, dd, J ) 11.4, 4.4
8056 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
Hz, H-7b), 3.40 (1H, dd, J ) 7.6, 3.2 Hz, H-4); 13C NMR (100
MHz, CDCl3) δ 141.30, 128.77, 128.61, 127.02, 81.67 (C-4),
76.81 (C-6), 76.34 (C-2), 75.99 (C-1), 69.55 (C-3), 65.39 (C-5),
59.99 (C-7), 58.10 (OCH3); ESI MS (calcd for C14H20O6, 284)
m/z (relative intensity) 307 (M + Na+, 100), 308 (M + Na+,
14), 591 (2M + Na+, 6).
(1R)-2,6-An h yd r o-1-p h en yl-4-O-m eth yl-7-d eoxy-7-iod o-
r-D-a ltr o-h ep titol (44).28 Iodination of 40 (670 mg, 2.36 mmol)
was achieved by following the same procedure described in
the preparation of 42. The product 44 (ca. 780 mg, 85% yield)
was purified by column chromatography (SiO2, EtOAc 20 to
60%, petroleum ether), but the product remained contaminated
with triphenylphosphine oxide. Attempts at further purifica-
tion were unsuccessful: 1H NMR (500 MHz, CDCl3) δ aromatic
region contaminated by TPPO, 4.89 (1H, dd, J ) 7.0, 3.7 Hz,
H-1), 4.14 (1H, dt, J ) 7.0, 3.3 Hz, H-5), 4.09-3.95 (3H, m,
H-3, H-6, OH-1), 3.61 (1H, t, J ) 7.7 Hz, H-2), 3.56 (1H, broad
s, OH-3), 3.51 (3H, s, OCH3), 3.38 (1H, dd, J ) 7.7, 3.7 Hz,
H-4), 3.23 (1H, dd, J ) 10.6, 6.6 Hz, H-7a), 3.12 (1H, dd, J )
10.6, 8.1 Hz, H-7b), 2.67 (1H, d, J ) 3.3 Hz, OH-5); 13C
NMR (75 MHz, CDCl3) δ Aromatic region contaminated by
TPPO, 80.83 (C-4), 76.46 (C-6), 76.41 (C-2), 75.85 (C-1), 69.38
(C-3), 66.79 (C-5), 58.19 (OCH3), 2.68 (C-7); ESI MS (calcd for
(1R)-2,6-An h yd r o-1-p h en yl-1,3,5,7-tetr a k is-O-a cetyl-4-
O-m eth yl-r-D-a ltr o-h ep titol (41). The C-glycoside 40 (40 mg,
0.14 mmol) was acetylated following the same reaction condi-
tions described for the preparation of 9 (EtOAc, 5 mL, DMAP,
5 mg and Ac2O, 0.2 mL). The product 41 was isolated in
quantitative yield: 1H NMR (500 MHz, CDCl3) δ 7.40-7.28
(5H, m), 6.36 (1H, d, J ) 9.8 Hz, H-1), 5.35 (1H, dd, J ) 4.3,
2.4 Hz, H-3), 5.04 (1H, dd, J ) 9.2, 3.1 Hz, H-5), 4.21 (1H, dt,
J ) 9.2, 2.4 Hz, H-6), 4.17-4.12 (2H, m, H-2 and H-7a), 3.89
(1H, dd, J ) 11.6, 2.4 Hz, H-7b), 3.75 (1H, t, J ) 3.7 Hz, H-4),
3.49 (3H, s, OCH3), 2.11 (3H, s, OAc), 2.10 (3H, s, OAc), 2.09
(3H, s, OAc), 1.91 (3H, s, OAc); 13C NMR (75 MHz, CDCl3) δ
170.49, 169.88, 169.85, 169.31, 137.57, 128.46, 128.39, 127.71,
76.66 (C-2), 76.46 (C-4), 72.76 (C-1), 68.06 (C-6), 67.67 (C-3),
67.38 (C-5), 62.97 (C-7), 59.31 (OCH3), 21.25, 21.06, 20.82; ESI
MS (calcd for C22H28O10, 452) m/z (relative intensity) 470 (M
+ NH4+, 100), 471 (M + NH4+, 26).
C
14H19IO5, 394) m/z (relative intensity) 412 (M + NH4+, 100),
413 (M + NH4+, 17), 811 (2M + Na+, 81), 812 (2M + Na+, 25).
(1R)-2,6-An h yd r o-1-p h en yl-4-O-m eth yl-7-d eoxy-r-D-a l-
tr o-h ep titol (45).29 The C-glycoside 45 was obtained via
radical deiodination of 44 in 75% yield following the same
procedure described for the preparation of 43. Alternatively,
45 was prepared via deprotection of the SEM ether by treating
43 with a 2/1 solution of methylene chloride/trifluoroacetic acid
(1.5 mL per 50 mg of starting material). After complete
deprotection of SEM ether was detected by TLC, toluene (2
mL per mL of reaction solution) was added, and the solvent
was removed under reduced pressure. A second cycle of
addition/evaporation of toluene afforded a pure sample of the
product 45 in quantitative yield as a white solid, without
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
eth oxym eth yl]-4-O-m eth yl-7-d eoxy-7-iod o-r-D-a ltr o-h ep -
titol (42).28 A mixture of the C-glycoside 39 (860 mg, 2.07
mmol), imidazole (456 mg, 6.7 mmol), triphenylphosphine (840
mg, 3.2 mmol), and iodine (863 mg, 3.4 mmol) in dry THF (35
mL) was stirred under reflux for 2 h. The solvent was re-
moved under reduced pressure, and the product was puri-
fied by column chromatography (SiO2, EtOAc 10-40%, petro-
leum ether), to isolate the colorless oil 42 (887 mg, 1.69
necessity of further purification: [R]25 ) -10.8 (c ) 0.65,
D
mmol, 82%): [R]25 ) -52.2 (c ) 1.7, CHCl3). Anal. Calcd for
CHCl3); mp 94-96 °C. Anal. Calcd for C14H20O5: C, 62.67; H,
D
1
1
7.51. Found: C, 62.71; H, 7.34. H NMR (500 MHz, CDCl3) δ
C
20H33IO6Si: C, 45.80; H, 6.34. Found: C, 45.97; H, 6.21. H
7.42 (2H, d, J ) 7.3 Hz), 7.35 (2H, t, J ) 7.3 Hz), 7.29 (1H, t,
J ) 7.3 Hz), 4.88 (1H, d, J ) 6.7 Hz, H-1), 4.15 (1H, dt, J )
7.3, 1.8 Hz, H-6), 3.94 (1H, t, J ) 8.5 Hz, H-3), 3.86 (1H, dd,
J ) 3.1, 1.8 Hz, H-5), 3.70 (1H, dd, J ) 8.5, 6.7 Hz, H-2), 3.49
(3H, s, OCH3), 3.43 (1H, dd, J ) 8.5, 3.1 Hz, H-4), 1.16 (3H, d,
J ) 7.3 Hz, H-7); 13C NMR (75 MHz, CDCl3) δ 141.30, 128.29,
127.86, 127.07, 81.04 (C-4), 76.26 (C-1), 74.74 (C-2), 73.02
(C-6), 70.05 (C-3), 68.94 (C-5), 57.67 (OCH3), 15.29 (C-7).
NMR (500 MHz, CDCl3) δ 7.38 (2H, d, J ) 7.3 Hz), 7.34 (2H,
d, J ) 7.3 Hz), 7.30 (1H, d, J ) 7.3 Hz), 4.87 (1H, d, J ) 7.9
Hz, H-1), 4.63 (1H, J ) 6.7 Hz, SEM), 4.54 (1H, J ) 6.7 Hz,
SEM), 4.12 (1H, dd, J ) 7.9, 4.3 Hz, H-5), 4.06 (1H, dt, J )
7.3, 2.4 Hz, H-3), 3.88 (1H, dt, J ) 7.3, 4.3 Hz, H-6), 3.73-
3.66 (2H, m, H-2 and SEM), 3.57 (3H, s, OCH3), 3.48-3.41
(2H, m, H-4 and SEM), 3.39 (1H, d, J ) 2.4 Hz, OH-3), 3.20
(1H, dd, J ) 10.4, 6.7 Hz, H-7a), 3.07 (1H, dd, J ) 10.4,
7.3 Hz, H-7b), 2.46 (1H, d, J ) 4.3 Hz, OH-5), 0.90-0.77
(2H, m, SEM), -0.01 (9H, s, SEM); 13C NMR (75 MHz, CDCl3)
δ 138.50, 128.41, 128.38, 128.34, 92.94 (SEM, OCH2O),
80.69 (C-4), 79.86 (C-1), 76.60 (C-2), 75.68 (C-6), 69.55
(C-3), 67.09 (C-5), 66.22 (SEM, OCH2CH2SiMe3), 58.55
(OCH3), 18.30 (SEM, OCH2CH2SiMe3), 2.92 (C-7), -1.09 (SEM,
Si(CH3)3).
(1R)-2,6-An h ydr o-1-ph en yl-1,3-O-ben zyliden e-4-O-m eth -
yl-7-d eoxy-r-D-a ltr o-h ep titol (46). A solution of C-glycoside
45 (14 mg, 0.05 mmol), benzaldehyde dimethyl acetal (0.08
mL, 0.05 mmol), and p-toluenesulfonic acid (1 crystal), dis-
solved in acetonitrile (2.5 mL), was stirred at room tempera-
ture for 2 h. Triethylamine (0.2 mL) was added, and the solvent
was removed under reduced pressure. The product 46 was
purified by column chromatography (SiO2, petroleum ether,
EtOAc 30%): 1H NMR (500 MHz, CDCl3) δ 7.57 (2H, d, J )
7.3 Hz), 7.48 (2H, d, J ) 7.3 Hz), 7.39-7.28 (6H, m), 5.85 (1H,
s, H-8), 4.79 (1H, d, J ) 8.5 Hz, H-1), 4.26-4.21 (2H, m, H-3
and H-6), 3.96 (1H, bd, J ) 3.1 Hz, H-5), 3.68 (1H, dd, J )
9.3, 3.1 Hz, H-4), 3.63-3.58 (4H, m, H-2 and OCH3), 2.75 (1H,
s, OH), 1.15 (2H, d, J ) 7.3 Hz, H-7); 13C NMR (75 MHz,
CDCl3) δ 138.36, 137.81, 128.99, 128.30, 127.42, 126.43, 101.62
(C-8), 81.34 (C-1), 79.38 (C-3 or C-6), 77.75 (C-4), 74.14 (C-3
or C-6), 71.36 (C-5), 70.08 (C-2), 59.04 (OCH3), 15.41 (C-7); ESI
MS (calcd for C22H28O5, 356) m/z (relative intensity) 379 (M +
Na+, 100), 380 (M + Na+, 21), 735 (2M + Na+, 62), 726 (2M +
Na+, 29).
2,6-An h yd r o-1-p h en yl-1-k eto-4-O-m eth yl-7-d eoxy-r-D-
a ltr o-h ep titol (47). DDQ was added (250 mg, 1.1 mmol) to
the C-glycoside 45 (250 mg, 0.93 mmol) dissolved in methylene
chloride (16 mL), and the mixture was stirred for 8 h under
gentle reflux. Additional DDQ (200 mg 0.88 mmol) was added,
and the mixture was stirred at room temperature overnight.
The solvent was removed under reduced pressure, and the
product was purified by column chromatography (alumina,
activated basic, Brockmann I; solvent, methanol 0-10%,
EtOAc). The ketone 47 (190 mg, 0.71 mmol) was isolated in
(1R )-2,6-An h yd r o-1-p h e n yl-1-O-[2-(t r im e t h ylsilyl)-
eth oxym eth yl]-4-O-m eth yl-7-deoxy-r-D-altr o-h eptitol (43).29
A mixture of 42 (100 mg, 0.19 mmol), tributyltin hydride (120
mg, 0.41 mmol) and AIBN (5 mg), in toluene (8 mL) was
refluxed for 2 h. The solvent was removed under reduced
pressure, and the product 43 (60 mg, 79% yield) was isolated
by column chromatography (SiO2, petroleum ether, EtOAc 10
to 40%) as a colorless oil: [R]25 ) -86.0 (c ) 1.5, CHCl3); 1H
D
NMR (500 MHz, CDCl3) δ 7.38 (2H, d, J ) 7.3 Hz), 7.32 (2H,
t, J ) 7.3 Hz), 7.28 (1H, t, J ) 7.3 Hz), 4.84 (1H, d, J ) 7.3
Hz, H-1), 4.63 (1H, d, J ) 6.7 Hz, SEM), 4.51 (1H, d, J ) 6.7
Hz, SEM), 4.08 (1H, dq, J ) 7.3, 1.8 Hz, H-6), 3.88 (1H, t, J )
8.5 Hz, H-3), 3.82 (1H, bq, J ) ∼3.1 Hz, H-5), 3.76-3.69 (2H,
m, H-2 and SEM), 3.53 (3H, s, OCH3), 3.48-3.42 (2H, m, H-4
and SEM), 2.43 (1H, d, J ) 3.1 Hz, OH-5), 1.10 (3H, d, J )
7.3 Hz, H-7), 0.95-0.77 (2H, m, SEM), -0.01 (9H, s, SEM);
13C NMR (75 MHz, CDCl3) δ 138.92, 128.34, 128.25, 128.13,
93.01 (SEM, OCH2O), 81.13 (C-4), 80.43 (C-1), 75.23 (C-2),
72.69 (C-6), 70.47 (C-3), 69.49 (C-5), 66.20 (SEM, OCH2CH2-
SiMe3), 58.14 (OCH3), 18.42(SEM, OCH2CH2SiMe3), 15.48
(C-7), -1.075 (SEM, Si(CH3)3); ESI MS (calcd for C20H38O6Si,
398) m/z (relative intensity) 416 (M + NH4+, 100), 417 (M +
NH4+, 31), 819 (2M + Na+, 15).
J . Org. Chem, Vol. 68, No. 21, 2003 8057

Pasetto and Franck
77% yield as an oil: 1H NMR (500 MHz, CDCl3) δ 7.97 (2H, d,
J ) 7.3 Hz), 7.57 (2H, t, J ) 7.3 Hz), 7.46 (1H, t, J ) 7.3 Hz),
4.71 (1H, d, J ) 6.7 Hz, H-2), 4.56 (1H, bq, J ) 5-7 Hz, H-3),
4.15 (1H, q, J ) 6.7 Hz, H-6), 3.81 (1H, bq, J ) 5.0-3.6 Hz,
H-5), 3.56 (1H, dd, J ) 7.3, 3.7 Hz, H-4), 3.45(3H, s, OCH3),
2.72 (1H, d, J ) 4.9 Hz, OH-3), 2.44 (1H, d, J ) 5.5 Hz, OH-
5), 1.40 (3H, d, J ) 6.7 Hz, H-7); 13C NMR (75 MHz, CDCl3) δ
197.90 (C-1), 136.04, 133.36, 129.13, 128.55, 79.96 (C-4), 77.17
(C-2), 72.68 (C-6), 69.34 (C-5), 68.03 (C-3), 58.32, 16.15 (C-7).
8 mL) was performed. The organic layer was dried, and the
solvent was removed under reduced pressure. The product
consisted of a mixture of starting material 48, the glycal 50,
and the two inseparable anomers R- and â-49 in a ratio
1/1/1/1. The glycal 50 was isolated by column chromatography
(SiO2, petroleum ether, EtOAc 5%): 1H NMR (500 MHz,
CDCl3) δ 7.85 (2H, d, J ) 7.3 Hz), 7.55 (1H, t, J ) 7.3 Hz),
7.44 (2H, t, J ) 7.3 Hz), 5.84 (1H, d, J ) 5.5 Hz, H-3), 4.29
(1H, dq, J ) 9.2, 6.7 Hz, H-6), 3.77 (1H, dd, J ) 5.5, 3.7 Hz,
H-4), 3.73 (1H, dd, J ) 9.2, 4.3 Hz, H-5), 3.48 (3H, s, OCH3),
1.41 (3H, d, J ) 6.7 Hz, H-7), 0.95 (9H, s), 0.142 (3H, s), 0.138
(3H, s); 13C NMR (75 MHz, CDCl3) δ 204.47, 152.11, 136.68,
132.79, 129.89, 128.25, 107.79, 72.98, 72.49, 57.70, 26.14,
18.53, 18.03, -3.79, -4.37, -3.79, -4.37.
2,6-An h yd r o-1-p h e n yl-1-k e t o-3,5-b is-O-t er t -b u t yld i-
m eth ylsilyl-4-O-m eth yl-7-d eoxy-r-D-a ltr o-h ep titol (48). A
mixture of the C-glycoside 47 (54 mg, 0.21 mmol), imidazole
(48 mg, 0.7 mmol), and TBDMSCl (105 mg, 0.7 mmol) in dry
DMF (2.5 mL) was stirred at room temperature under nitrogen
overnight (12 h). Water (8 mL) was added, and the mixture
was extracted with EtOAc (3 × 8 mL). The organic layer was
dried over sodium sulfate, and the solvent was removed under
reduced pressure. Column chromatography (SiO2, petroleum
ether, EtOAc 5%) afforded the product 48 (oil, 97 mg, 93%
(2S)-3,7-An h yd r o-2-p h en yl-4,6-bis-O-ter t-bu tyld im eth -
ylsilyl-5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitol (52) a n d (2R)-
3,7-An h yd r o-2-p h en yl-4,6-bis-O-ter t-bu tyld im eth ylsilyl-
5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitol (53).35 To a solution
of 49 (105 mg, 0.21 mmol) in acetone (8 mL) at 0 °C (ice bath)
were added 4-methylmorpholine-N-oxide (50 wt % in H2O, 0.15
mL, 0.72 mmol) and osmium tetroxide (2.5 wt % in t-BuOH,
0.2 mL, 0.016 mmol). The mixture was stirred at 0 °C for 6 h
and then at room temperature overnight (14 h). Sodium sulfite
(ca. 10 mg) was added, and the mixture was stirred for 1 h.
Ethyl acetate was added (20 mL), and the mixture was dried
over sodium sulfate. The mixture was filtered, and the filtrate
was concentrated under reduced pressure. The two diastere-
omers 52 (white solid, 72 mg, 0.14 mmol, 66%) and 53
(colorless oil, 18 mg, 0.034 mmol, 16%) were isolated by column
chromatography (SiO2, EtOAc 10%, petroleum ether). 52: Rf
yield): [R]25 ) +48.9 (c ) 0.9, CHCl3). Anal. Calcd for
D
1
C
26H48O5Si2: C, 63.11; H, 9.37. Found: C, 63.11; H, 9.39. H
NMR (500 MHz, CDCl3) δ 7.93 (2H, d, J ) 7.3 Hz), 7.51 (1H,
t, J ) 7.3 Hz), 7.42 (2H, t, J ) 7.3 Hz), 4.74 (1H, dd, J ) 4.9,
3.0 Hz, H-3), 4.61 (1H, d, J ) 2.4 Hz, H-2), 3.91 (1H, quintet,
J ) 6.1 Hz, H-6), 3.82 (1H, dd, J ) 7.9, 2.4 Hz, H-5), 3.28 (4H,
s, OCH3 and H-4), 1.17 (3H, d, J ) 6.1 Hz, H-7), 0.92 (9H, s),
0.82 (9H, s), 0.11 (3H, s), 0.10 (3H, s), 0.09 (3H, s), 0.07 (3H,
s); 13C NMR (75 MHz, CDCl3) δ 199.33, 137.21, 132.42, 128.67,
128.24, 82.02 (C-2), 81.88 (C-4), 71.10 (C-5), 70.10 (C-6), 69.59
(C-3), 58.29(OCH3), 26.10, 25.96, 18.43, 18.34, 17.87, -3.22,
0.24 (PE/EtOAc, 8/2); [R]25 ) +27.0 (c ) 0.8, CHCl3); mp
-3.99, -4.34, -4.39, -4.50; ESI MS (calcd for C26H46O5Si2,
D
494) m/z (relative intensity) 495 (M + H+, 20), 512 (M + NH4
,
+
69-71 °C. Anal. Calcd for C27H50O6Si2: C, 61.55; H, 9.57.
100), 513 (M + NH4+, 40).
1
Found: C, 61.30; H, 9.52. H NMR (500 MHz, CDCl3) δ 7.46
(2H, d, J ) 7.3 Hz), 7.37 (2H, t, J ) 7.3 Hz), 7.26 (1H, t, J )
7.3 Hz), 5.76 (1H, s, OH-2), 4.42 (1H, dq, J ) 9.2, 6.1 Hz, H-7),
4.09 (1H, dd, partially covered by s at 4.08 ppm, J ) 4.3 Hz,
H-1a), 4.08 (1H, s, H-3), 3.87 (1H, dd, J ) 11.0, 8.5 Hz, H-1b),
3.75 (1H, dd, J ) 9.2, 3.1 Hz, H-6), 3.67 (1H, d, J ) 3.7 Hz,
H-4), 3.56 (3H, s, OCH3), 3.26 (1H, t, J ) 3.1 Hz, H-5), 2.39
(1H, dd, J ) 8.5, 4.9 Hz, OH-1), 1.23 (3H, d, J ) 6.1 Hz, H-8),
0.91 (9H, s), 0.80 (9H, s), 0.10 (3H, s), 0.08 (3H, s), -0.25 (3H,
s), -0.28 (3H, s); 13C NMR (100 MHz, CDCl3) δ 143.67, 128.73,
127.38, 125.79, 83.69 (C-3), 81.93 (C-5), 79.02 (C-2), 71.53
(C-6), 70.13 (C-1), 68.96 (C-7), 68.54 (C-4), 60.20 (OCH3), 25.99,
25.81, 19.10, 18.19, 17.91, -3.84, -4.57, -4.91, -5.10; ESI MS
(calcd for C27H50O6Si2, 526) m/z (relative intensity) 527 (M +
3,7-An h yd r o-1,2,8-tr id eoxy-2-p h en yl-4,6-bis-O-ter t-bu -
tyldim eth ylsilyl-5-O-m eth yl-r-D-altr o-oct-1-en itol (r-49).34
To a slurry of Nysted reagent (20 wt % suspension in THF,
320 mg, 0.7 mmol) and ketone 48 (74 mg, 0.15 mmol) in dry
THF (2 mL) at -78 °C under N2 was added dropwise a solution
of TiCl4 (1 M in CH2Cl2, 0.6 mL). The mixture turned yellow
and was warmed to room temperature and stirred overnight
(14 h). The resulting dark slurry was then cooled in an ice
bath, and triethylamine (0.5 mL) was added, followed by silica
gel. The mixture was warmed to room temperature and was
filtered through a plug of silica gel using ethyl acetate as a
wash. The filtrate was concentrated and the product R-49 (oil,
54 mg, 0.11 mmol, 73%) was isolated by column chromatog-
H+, 100), 528 (M + H+, 42). 53: Rf 0.3 (PE/EtOAc, 8/2); [R]25
raphy (SiO2, EtOAc 5%, petroleum ether): [R]25 ) +3.6 (c )
D
D
1
) -37.9 (c ) 0.8, CHCl3); H NMR (500 MHz, CDCl3) δ 7.76
0.83, CHCl3). Anal. Calcd for C27H48O4Si2: C, 65.80; H, 9.82.
1
(2H, d, J ) 7.3 Hz), 7.28 (2H, t, J ) 7.3 Hz), 7.23 (1H, t, J )
7.3 Hz), 4.68 (1H, s, OH-2), 4.17 (1H, t, J ) 9.2 Hz, H-4), 4.13
(1H, dq, J ) 7.3, 2.4 Hz, H-7), 3.97 (1H, d, J ) 9.2 Hz, H-3),
3.94 (1H, t, J ) 2.4 Hz, H-6), 3.85 (1H, broad t, J ) 11 Hz,
H-1a), 3.48 (1H, dd, J ) 11.0, 3.7 Hz, H-1b), 3.26 (1H, dd,
partially covered by s at 3.25 ppm, J ) 2.4 Hz, H-5), 3.25 (3H,
s, OCH3), 2.30 (1H, dd, J ) 9.8, 3.7 Hz, OH-1), 1.29 (3H, d, J
) 7.3 Hz, H-8), 0.90 (9H, s), 0.82 (9H, s), 0.09 (3H, s), 0.04
(3H, s), -0.02 (3H, s), -0.21 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 141.99, 127.83, 127.33, 127.28, 81.83 (C-5), 78.76
(C-2), 75.16 (C-3), 74.69 (C-7), 70.96 (C-4), 69.78 (C-6), 69.47
(C-1), 56.00 (OCH3), 26.54, 25.86, 18.70, 18.25, 15.05, -3.38,
-4.46, -4.57, -4.64; ESI MS (calcd for C27H50O6Si2, 526) m/z
(relative intensity) 527 (M + H+, 100), 528 (M + H+, 42).
Found: C, 65.52; H, 9.79. H NMR (500 MHz, CDCl3) δ 7.58
(2H, d, J ) 7.3 Hz), 7.29 (2H, t, J ) 7.3 Hz), 7.24 (1H, t, J )
7.3 Hz), 5.48 (1H, s, H-1a), 5.37 (1H, s, H-1b), 4.40 (1H, d, J )
7.0 Hz, H-3), 4.17 (1H, dq, J ) 6.7, 4.3 Hz, H-7), 4.10 (1H, t,
J ) 7.0 Hz, H-4), 3.92 (1H, dd, J ) 4.3, 3.0 Hz, H-6), 3.25 (3H,
s, OCH3), 3.19 (1H, dd, J ) 7.0, 3.0 Hz, H-5), 1.30 (3H, d, J )
6.7 Hz, H-8), 0.94 (9H, s), 0.81 (9H, s), 0.10 (3H, s), 0.09 (3H,
s), -0.08 (3H, s), -0.24 (3H, s); 13C NMR (100 MHz, CDCl3) δ
146.11, 139.63, 128.16, 127.61, 127.51, 116.80 (C-1), 82.68
(C-5), 79.29 (C-3), 72.40 (C-7), 70.83 (C-6), 69.84 (C-4), 57.62-
(OCH3), 26.17, 26.01, 18.40, 18.36, 16.17, -4.18, -4.31, -4.63,
-4.86; ESI MS (calcd for C27H48O4Si2, 492) m/z (relative
intensity) 493 (M + H+, 55), 494 (M + H+, 23), 510 (M + NH4
,
+
100), 511 (M + NH4+, 44).
(2R)-3,7-An h yd r o-2-p h en yl-4,6-bis-O-ter t-bu tyld im eth -
ylsilyl-5-O-m eth yl-8-d eoxy-r-D-a ltr o-octita l (54) a n d (2S)-
3,7-An h yd r o-2-p h en yl-4,6-bis-O-ter t-bu tyld im eth ylsilyl-
5-O-m eth yl-8-d eoxy-r-D-a ltr o-octita l (55).39 A mixture of
the alcohol 52 or 53 (1 equiv), freshly prepared polymer-bound
bromite(I) (6 equiv), and a catalytic amount of TEMPO (2,2,6,6-
tetramethyl-1-piperidinyloxy, free radical) in dry methylene
chloride (60 mL/mmol of alcohol) was stirred at room temper-
ature until completion of the reaction (monitored by TLC,
normally less than 2 h). The mixture was filtered, the resin
2,6-An h yd r o-1-p h en yl-1-k eto-3,7-d id eoxy-4-O-m eth yl-
5-O-ter t-bu tyld im eth ylsilyl-D-a ltr o-h ep t-2-en itol (50). To
a solution of methyltriphenylphosphonium bromide (50 mg,
0.14 mmol) in dry THF (2.5 mL) was added n-BuLi (1.6 M in
hexanes, 0.08 mL) at -10 °C under nitrogen. The yellow
mixture was stirred at -10 °C for ca. 1 h, and then the
C-glucoside 48 (20 mg, 0.41 mmol, in 2.5 mL dry THF) was
added dropwise. The mixture was stirred at -10 °C for 1 h
and at room temperature for 2 h. A saturated solution of
NH4Cl (8 mL) was added, and an extraction with EtOAc (3 ×
8058 J . Org. Chem., Vol. 68, No. 21, 2003

Northwest Quadrant of Altromycin B
was washed with methylene chloride, and the combined filtrate
and organic washings were concentrated under reduced pres-
sure to yield the diastereomeric aldehydes (quantitative yield)
as oils. Further purification was unnecessary, and the products
equiv) was added tetrabutylammonium fluoride (1 M in THF,
ca. 3 equiv), and the mixture was stirred at room temperature
until TLC indicated completion of the reaction. The solvent
was removed under reduced pressure, and the product 2 or 3
was purified by column chromatography (SiO2, petroleum
ether, EtOAc 50%). The yield was typically >93%. 2: 1H NMR
(500 MHz, CDCl3) δ 7.81 (2H, d, J ) 7.0 Hz), 7.39 (2H, t,
J ) 7.0 Hz), 7.32 (1H, t, J ) 7.0 Hz), 4.37 (1H, d, J ) 9.2 Hz,
H-3), 4.27 (1H, dq, J ) 7.0, 1.3 Hz, H-7), 4.13 (1H, t, J )
9.1 Hz, H-4), 3.89 (1H, dd, J ) 3.2, 1.9 Hz, H-6), 3.80 (3H, s,
CO2CH3), 3.44 (3H, OCH3), 3.38 (1H, dd, J ) 8.9, 3.2 Hz, H-5),
1.32 (3H, d, J ) 7.0 Hz, H-8); 13C NMR (100 MHz, CDCl3) δ
173.68 (C-1), 137.51, 128.71, 128.62, 126.11, 80.84 (C-5), 79.96
(C-2), 77.05 (C-3), 73.48 (C-7), 69.16 (C-6), 67.39 (C-4), 58.12
(OCH3), 53.40 (CO2CH3), 15.14 (C-8); ESI MS (calcd for
were directly subjected to the next step. 54: [R]25 ) +14.6 (c
D
) 0.7, CHCl3); 1H NMR (500 MHz, CDCl3) δ 9.69 (1H, s, H-1),
7.54 (2H, t, J ) 7.5 Hz), 7.38 (2H, t, J ) 7.5 Hz), 7.29 (1H, t,
J ) 7.5 Hz), 6.03 (1H, s, OH), 4.50 (1H, s, H-3), 4.37 (1H, dq,
J ) 9.6, 6.2 Hz, H-7), 3.74 (1H, dd, J ) 9.6, 2.7 Hz, H-6), 3.66
(1H, d, J ) 3.4 Hz, H-4), 3.57 (3H, s, OCH3), 3.27 (1H, t, J )
3.4 Hz, H-5), 1.19 (3H, d, J ) 6.2 Hz, H-8), 0.91 (9H, s), 0.81
(9H, s), 0.09 (3H, s), 0.08 (3H, s), -0.22 (3H, s), -0.26 (3H, s);
13C NMR (100 MHz, CDCl3) δ 201.29 (C-1), 138.29, 128.87,
128.10, 126.04, 84.59 (C-2), 82.62 (C-3), 81.84 (C-5), 71.52
(C-6), 69.49 (C-7), 67.93 (C-4), 60.23 (OCH3), 25.97, 25.79,
19.00, 18.17, 17.90, -3.87, -4.61, -4.93, -5.04; ESI MS (calcd
C
16H22O7, 326) m/z (relative intensity) 349 (M + Na+, 100),
350 (M + Na+, 19), 675 (2M + Na+, 38), 676 (2M + Na+, 15).
3: 1H NMR (500 MHz, CDCl3) δ 7.61 (2H, d, J ) 7.6 Hz), 7.31
(2H, t, J ) 7.6 Hz), 7.24 (1H, t, J ) 7.6 Hz), 4.47 (1H, d, J )
9.5 Hz, H-3), 4.27 (1H, t, J ) 9.5 Hz, H-4), 3.85 (2H, broad s,
H-6 and H-7), 3.69 (3H, s, CO2CH3), 3.59 (3H, s, OCH3), 3.48
(1H, dd, J ) 9.5, 3.1 Hz, H-5), 1.12 (3H, d, J ) 5.7 Hz, H-8);
13C NMR (100 MHz, CDCl3) δ 173.27 (C-1), 140.68, 128.04,
127.61, 126.35, 81.61 (C-5), 78.56 (C-2), 75.59 (C-3), 73.43
(C-7), 69.85 (C-6), 67.09 (C-4), 58.10 (OCH3), 53.16 (CO2CH3),
14.54 (C-8); ESI MS (calcd for C16H22O7, 326) m/z (relative
intensity) 349 (M + Na+, 100), 350 (M + Na+, 19), 675 (2M +
Na+, 38), 676 (2M + Na+, 14).
for C27H48O6Si2, 524) m/z (relative intensity) 525 (M + H+, 92),
526 (M + H+, 36), 542 (2M + NH4+, 100), 543 (2M + NH4
,
+
34). 55: [R]25 ) +37.6 (c ) 0.85, CHCl3); 1H NMR (500 MHz,
D
CDCl3) δ 9.53 (1H, s, H-1), 7.57 (2H, d, J ) 7.5 Hz), 7.37 (2H,
t, J ) 7.5 Hz), 7.29 (1H, t, J ) 7.5 Hz), 4.34 (1H, d, J ) 2.7
Hz, H-3), 4.14 (1H, quintet, J ) 6.8 Hz, H-7), 4.08 (1H, t, J )
3.8 Hz, H-4), 3.79 (1H, dd, J ) 7.5, 2.7 Hz, H-6), 3.56 (3H, s,
OCH3), 3.38 (1H, dd, J ) 4.8, 2.7 Hz, H-5), 1.00 (3H, d, J )
6.8 Hz, H-8), 0.91 (9H, s), 0.90 (9H, s), 0.13 (3H, s), 0.10 (3H,
s), 0.09 (3H, s), 0.07 (3H, s); 13C NMR (100 MHz, CDCl3) δ
201.05 (C-1), 137.07, 128.57, 127.91, 126.58, 83.92 (C-2), 82.22
(C-5), 80.99 (C-3), 71.42 (C-6), 70.31 (C-7), 70.17 (C-4), 59.50
(OCH3), 26.09, 25.99, 18.23, 18.21, 17.69, -4.00, -4.30, -4.54,
-4.60.
(2R)-Meth yl-3,7-a n h yd r o-2-p h en yl-2,4-O-ben zylid en e-
5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitola te (58). A solution of
C-glycoside 2 (5 mg, 0.015 mmol), benzaldehyde dimethyl
acetal (0.07 mL), and p-toluenesulfonic acid (1 crystal), dis-
solved in acetonitrile (1.5 mL), was stirred at room tempera-
ture for 3 h. Acidic resin was added, and the mixture was
filtered. The solvent was removed under reduced pressure: 1H
NMR (500 MHz, CDCl3) δ 7.66 (2H, d, J ) 8.3 Hz), 7.60 (2H,
d, J ) 8.3 Hz), 7.43-7.29 (6H, m), 6.13 (1H, s, H-9), 4.57 (1H,
t, J ) 9.5 Hz, H-4), 4.39 (1H, q, J ) 8.3 Hz, H-7), 3.94 (1H,
broad s, H-6), 3.78-3.75 (4H, m, H-3 and CO2CH3), 3.58-3.55
(4H, m, H-5 and OCH3), 1.17 (3H, d, J ) 7 Hz, H-8).
(2S)-Meth yl-3,7-a n h yd r o-2-p h en yl-2,4-O-ben zylid en e-
5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitol (59). To a solution of
58 (5 mg, 0.012 mmol), in CH2Cl2 (1.5 mL) was added
DIBAL-H (1 M in hexanes, 28 µL) at -78 °C under nitrogen.
The mixture was stirred at -78 °C for 1.5 h and then at room
temperature for 1.5 h. EtOAc (0.2 mL) was added, and the
mixture was stirred for 30 min. The solvent was removed
under reduced pressure, and the product was purified by
column chromatography (SiO2, petroleum ether, EtOAc 50%):
1H NMR (500 MHz, CDCl3) δ 7.74 (2H, d, J ) 7.6 Hz), 7.62
(2H, d, J ) 7 Hz), 7.44-7.34 (5H, m), 7.29 (1H, t, J ) 7 Hz),
6.22 (1H, s, H-9), 4.56 (1H, dd, J ) 12.7, 5.7 Hz, H-1a), 4.48
(1H, t, J ) 10 Hz, H-4), 4.35 (1H, t, J ) 7.6 Hz, H-7), 4.31
(1H, dd, J ) 12.7, 7.0 Hz, H-1b), 3.93 (1H, d, J ) 3.2 Hz, H-6),
3.76 (1H, d, J ) 10 Hz, H-3), 3.56 (1H, s, OCH3), 3.52 (1H, dd,
J ) 9.5, 3.2 Hz, H-5), 1.69 (1H, t, J ) 7 Hz, OH-1), 1.16 (3H,
d, J ) 7.6 Hz, H-8).
(2R)-Meth yl-3,7-a n h yd r o-2-p h en yl-2,4-O-(4-br om oben -
zyliden e)-5-O-m eth yl-8-deoxy-r-D-altr o-octitolate (60) an d
(2S)-Met h yl-3,7-a n h yd r o-2-p h en yl-2,4-O-(4-b r om ob en -
zylid en e)-5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitola te (61). A
solution of C-glycoside 2 or 3 (5 mg, 0.015 mmol), p-bromoben-
zaldehyde dimethyl acetal (8 µL, 0.039 mmol), and p-toluene-
sulfonic acid (1 crystal), dissolved in acetonitrile (1.5 mL), was
stirred at room temperature for 2 h. Triethylamine (0.2 mL)
was added, and the solvent was removed under reduced
pressure. The product 60 or 61 (quantitative yield) was
purified by column chromatography (SiO2, petroleum ether,
EtOAc 40%). 60: 1H NMR (500 MHz, CDCl3) δ 7.63 (2H, dd,
J ) 8.3, 1.9 Hz), 7.53 (2H, d, J ) 8.3 Hz), 7.47 (2H, d, J ) 8.3
Hz), 7.37-7.31 (3H, m), 6.12 (1H, s, H-9), 4.53 (1H, t, J ) 9.5
Hz, H-4), 4.40 (1H, q, J ) 7.0 Hz, H-7), 3.94 (1H, broad s, H-6),
(2R)-Met h yl-3,7-a n h yd r o-2-p h en yl-4,6-b is-O-ter t-b u -
t yld im e t h ylsilyl-5-O-m e t h yl-8-d e oxy-r-D-a lt r o-oct it o-
la te (56) a n d (2S)-Meth yl-3,7-a n h yd r o-2-p h en yl-4,6-bis-
O-ter t-bu tyld im eth ylsilyl-5-O-m eth yl-8-d eoxy-r-D-a ltr o-
octitola te (57).40 The aldehyde 54 or 55 was dissolved in
MeOH (35 mL/mmol of aldehyde) and cooled at 0 °C (ice bath).
Iodine (3 equiv) was added, followed by dropwise addition of
a KOH solution in methanol (1.2 M, 8 equiv). The mixture was
stirred at low temperature for 15 min and then from 0 °C to
room temperature for 30 min. The reaction was quenched by
addition of solid ammonium chloride, and the solvent was
removed under reduced pressure. An extraction with EtOAc/
saturated NH4Cl yielded the product 56 or 57, which can be
directly employed in the next step. Otherwise, analytically
pure sample could be obtained via column chromatography
(SiO2, EtOAc 5%, petroleum ether). 56: 1H NMR (500
MHz, CDCl3) δ 7.71 (2H, d, J ) 7.6 Hz), 7.36 (2H, t, J )
7.6 Hz), 7.29 (1H, t, J ) 7.6 Hz), 5.80 (1H, s, OH), 4.60 (1H,
broad s, H-3), 4.37 (1H, dq, J ) 8.9, 6.3 Hz, H-7), 3.77 (3H, s,
CO2CH3), 3.76 (1H, dd, partially covered by s at 3.77 ppm, J
) 2.6 Hz, H-6), 3.69 (1H, dd, J ) 3.2, 1.3 Hz, H-4), 3.55 (3H,
s, OCH3), 3.26 (1H, t, J ) 3.2 Hz, H-5), 1.21 (3H, d, J ) 6.3
Hz, H-8), 0.90 (9H, s), 0.80 (9H, s), 0.09 (3H, s), 0.07 (3H, s),
-0.22 (3H, s), -0.34 (3H, s); 13C NMR (100 MHz, CDCl3) δ
173.09 (C-1), 139.83, 128.62, 128.12, 126.26, 83.21 (C-3), 82.55
(C-2), 82.09 (C-5), 71.85 (C-6), 69.82 (C-7), 67.93 (C-4), 60.20
(OCH3), 53.02 (CO2CH3), 25.97, 25.86, 18.84, 18.16, 17.91,
-3.81, -4.64, -4.89, -5.07; ESI MS (calcd for C28H50O7Si2,
554) m/z (relative intensity) 555 (M + H+, 100), 556 (M + H+,
43). 57: 1H NMR (500 MHz, CDCl3) δ 7.68 (2H, d, J ) 7.6
Hz), 7.34 (2H, t, J ) 7.6 Hz), 7.26 (1H, covered by CHCl3 at
7.26 ppm), 6.05 (1H, broad s, OH), 4.49 (1H, s, H-3), 4.32 (1H,
dq, J ) 8.9, 6.3 Hz, H-7), 4.07 (1H, d, J ) 3.2 Hz, H-4), 3.76
(1H, dd, J ) 8.9, 3.2 Hz, H-6), 3.73 (3H, s, CO2CH3), 3.62 (3H,
s, OCH3), 3.41 (1H, t, J ) 3.2 Hz, H-5), 0.99, (3H, d, J ) 6.3
Hz, H-8), 0.92 (9H, s), 0.91 (9H, s), 0.16 (3H, s), 0.12 (3H, s),
0.09 (3H, s), 0.07 (3H, s).
(2R)-Meth yl-3,7-an h ydr o-2-ph en yl-5-O-m eth yl-8-deoxy-
r-D-a ltr o-octitola te (2) a n d (2S)-Meth yl-3,7-a n h yd r o-2-
p h en yl-5-O-m eth yl-8-d eoxy-r-D-a ltr o-octitola te (3). To a
solution of C-glycoside 56 or 57 dissolved in THF (1 mL per
0.01 mmol of starting material) in the presence of AcOH (0.5
J . Org. Chem, Vol. 68, No. 21, 2003 8059

Pasetto and Franck
3.78 (3H, s, CO2CH3), 3.77 (1H, d, H-3, partially overlapped
with s at 3.78 ppm), 3.56 (3H, s, OCH3), 3.55 (1H, dd, J ) 3.2
Hz, H-5, partially overlapped with s at 3.56 ppm), 2.62 (1H,
d, J ) 2.5 Hz, OH), 1.19 (3H, d, J ) 7.0 Hz, H-8); 13C NMR
(100 MHz, CDCl3) δ 170.28 (C-1), 139.19, 136.72, 131.63,
128.46, 128.34, 128.22, 125.95, 97.86 (C-9), 81.38 (C-2), 78.12
(C-5), 75.55 (C-4), 74.43 (C-7), 72.17 (C-3), 70.76 (C-6), 58.79
(OCH3), 52.84 (CO2CH3), 14.74 (C-8). 61: 1H NMR (500 MHz,
CDCl3) δ 7.96 (2H, d, J ) 8.9 Hz), 7.49 (2H, d, J ) 8.3 Hz),
7.43-7.33 (5H, m), 5.57 (1H, s, H-9), 4.47 (1H, q, J ) 7.0 Hz,
H-7), 4.44-4.38 (2H, m, H-3 and H-4), 3.99 (1H, d, J ) 1.9
Hz, H-6), 3.72 (3H, s, CO2CH3), 3.62 (1H, dd, J ) 8.3, 3.2 Hz,
H-5), 3.53 (3H, s, OCH3), 2.60 (1H, s, OH), 1.38 (3H, d, J )
7.0 Hz, H-8); 13C NMR (100 MHz, CDCl3) δ 170.53 (C-1),
136.41, 135.67, 131.62, 129.11, 128.87, 128.78, 128.27, 123.35,
95.86 (C-9), 81.89 (C-2), 78.21 (C-5), 74.26 (C-3 or C-7),
74.06 (C-3 or C-7), 71.36 (C-4), 70.72 (C-6), 58.90 (OCH3), 53.26
(CO2CH3), 14.56 (C-8).
Ack n ow led gm en t. This research was supported by
grant NIH GM 60271. The infrastructure of the Hunter
College Chemistry Department is supported by an
RCMI grant NIH RR03037. We are indebted to Dr.
Michael Blumenstein for assistance with some NMR
experiments and to Dr. Clifford E. Soll for the mass
spectra. We thank Abbott Laboratories for a sample of
Altromycin B.
Su p p or tin g In for m a tion Ava ila ble: Table outlining
reaction conditions employed in the hydroboration of exo-glycal,
variable temperature 13C NMR spectra of the compound 39,
NOESY spectrum of 59, 1H and 13C NMR spectra, and CD
spectra of 60, 61, and 62. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O034607K
8060 J . Org. Chem., Vol. 68, No. 21, 2003