α-selective sialylations at -78°C in nitrile solvents with a 1-adamantanyl thiosialoside

Article abstract of DOI:10.1021/jo7012912

(Chemical Equation Presented) Novel 1-adamantanylthio sialosides were synthesized and coupled to acceptors under NIS/TfOH promotion conditions. These donors showed higher reactivity than the phenylthio sialosides and could be activated by NIS/TfOH in nitr

Full text of DOI:10.1021/jo7012912

N-acetyl-5-N,4-O-oxazolidinone-protected 2-phenylthio sialoside
donor 1 gave excellent yields and R-selectivities in linking to
various primary alkyl and carbohydrate acceptors under the NIS/
TfOH in situ activation conditions at -40 °C in dichloromethane
(Scheme 1).3 Importantly, following glycosylation, the oxazo-
lidinone group was readily cleaved under mild conditions
leaving the acetamide intact.3 Similar investigations were also
reported by the Takahashi and De Meo groups with N-desacetyl
analogues of 1, but harsher conditions were required for cleavage
of the oxazolidinone moiety.4
r-Selective Sialylations at -78 °C in Nitrile
Solvents with a 1-Adamantanyl Thiosialoside
David Crich*,† and Wenju Li
Department of Chemistry, UniVersity of Illinois at Chicago,
845 West Taylor Street, Chicago, Illinois 60607-7061
dcrich@chem.wayne.edu
ReceiVed June 18, 2007
SCHEME 1. Sialylations with Phenylthioglycoside 1
Novel 1-adamantanylthio sialosides were synthesized and
coupled to acceptors under NIS/TfOH promotion conditions.
These donors showed higher reactivity than the phenylthio
sialosides and could be activated by NIS/TfOH in nitrile
solvents at -78 °C to afford improved R-sialylations. With
the N-acetyl-5-N,4-O-oxazolidinone-protected 1-adamanta-
nylthio sialyl donor high R-selectivities could be achieved
in the sialylations of both primary and sterically hindered
secondary acceptors, including the important galactose 3-OH
acceptors.
In an attempt to increase the R-selectivities of the sialylations
of 1 with secondary sugar acceptors by means of the nitrile
effect,5 glycosylations promoted by NIS/TfOH were attempted
in nitrile solvents at -40 °C. However, no reaction was
observed. Noting the work of Oscarson and Lahmann on the
reactivityorderofvariousthioglycosides(glucoseandgalactose),6-8
we turned our attention to the use of more reactive thiosialoside
donors, which could possibly be activated in nitrile solvents at
low temperature when improved R-selectivities could be
anticipated.
Here we describe an investigation into the sialylations of
1-adamantanyl thiosialoside donors 2 and 3. The 1-adamantanyl
group was chosen because of its greater electron donating
properties compared to Oscarson’s preferred cyclohexyl group,
and the solid (mp 99-106 °C) nonvolatile nature of 1-adaman-
tanethiol, the precursor for the installation of 1-adamantanylthio
leaving group, which reduces the odor problem common to most
thiols.9
Oligosaccharides and glycoconjugates incorporating sialic
acid residues are ubiquitous in high animals and human beings
and play important roles in a wide variety of biological
processes.1 Over the years, considerable efforts have been spent
on the development of sialoside donors bearing various leaving
groups for efficient installation of R-sialyl linkages, among
which 2-sulfide donors of Neu5Ac, including S-alkyl (methyl,
ethyl) and S-aryl (phenyl and substituted phenyl) sialosides, have
been widely applied.2 In a previous report, we noted that an
† Current address: Department of Chemistry, Wayne State University, 5101
Cass Ave, Detroit, MI 48202.
(1) (a) Dwek, R. A. Chem. ReV. 1996, 96, 683. (b) Lis, H.; Sharon, N.
Chem. ReV. 1998, 98, 637. (c) Mammen, M.; Choi, S.-K.; Whitesides, G.
M. Angew. Chem., Int. Ed. 1998, 37, 2754. (d) Simanek, E. E.; McGarvey,
G. J.; Jablonowski, J. A.; Wong, C.-H. Chem. ReV. 1998, 98, 833. (e)
Ørntoft, T. F.; Vestergaard, E. M. Electrophoresis 1999, 20, 362.
(2) (a) Boons, G.-J.; Demchenko, A. V. Chem. ReV. 2000, 100, 4539.
(b) Ress, D. K.; Linhardt, R. J. Curr. Org. Synth. 2004, 1, 31. (c) Boons,
G. J.; Demchenko, A. V. In Carbohydrate-based Drug DiscoVery; Wong,
C. H., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Vol. 1, pp 55. (d)
Kiso, M.; Ishida, H.; Ito, H. In Carbohydrates in Chemistry and Biology;
Ernst, B., Hart, G. W., Sinay¨, P., Eds.; Wiley-VCH: Weinheim, Germany,
2000; Vol. 1, pp 345. (e) Halcomb, R. L.; Chappell, M. D. In Glycochem-
istry: Principles, Synthesis, and Applications; Wang, P. G., Bertozzi, C.
R., Eds.; Dekker: New York, 2001; pp 177. (f) Toshima, K.; Tatsuta, K.
Chem. ReV. 1993, 93, 1503. (g) Hanashima, S.; Castagner, B.; Esposito,
D.; Nokami, T.; Seeberger, P. H. Org. Lett. 2007, 9, 1777. (h) Roy, R.
Top. Curr. Chem. 1997, 187, 241. (i) Hasegawa, A. In Modern Methods in
Carbohydrate Synthesis; Khan, S. H., O’Niell, R. A., Eds.; Harwood:
Amsterdam, The Netherlands, 1996; pp 277. (j) Hasegawa, A.; Kiso, M. In
PreparatiVe Carbohydrate Chemistry; Hanessian, S., Ed.; Dekker: New
York, 1997; pp 357.
(3) Crich, D.; Li, W. J. Org. Chem. 2007, 72, 2387.
(4) (a) Tanaka, H.; Nishiura, Y.; Takahashi, T. J. Am. Chem. Soc. 2006,
128, 7124. (b) Farris, M. D.; De Meo, C. Tetrahedron Lett. 2007, 48, 1225.
(5) (a) Hasegawa, A.; Ohki, H.; Nagahama, T.; Ishida, H. Carbohydr.
Res. 1991, 212, 277. (b) Schmidt, R. R.; Ru¨cker, E. Tetrahedron Lett. 1980,
21, 1421. (c) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694.
(6) Lahmann, M.; Oscarson, S. Can. J. Chem. 2002, 80, 889.
(7) It was found that the cyclohexylthio group was about three times as
reactive as the ethylthio group, which in turn was twice as reactive as the
methylthio group. The phenylthio donors were found to be even less reactive
than the methylthio donors, whereas p-halophenylthio donors were inert
under the DMTST promotion conditions, but could be activated by NIS/
TfOH.6
(8) Roy, R.; Andersson, F. O.; Letellier, M. Use of electron-rich aryl
thiosialosides. Tetrahedron Lett. 1992, 33, 6053.
(9) Li, Z.; Gildersleeve, J. C. Use of adamantanyl thioglycosides to
suppress thioglycoside transfer. J. Am. Chem. Soc. 2006, 128, 11612.
10.1021/jo7012912 CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/07/2007
7794
J. Org. Chem. 2007, 72, 7794-7797

The penta-acetate derivative 410 of neuraminic acid was
reacted with 1-adamantanethiol in the presence of BF3‚Et2O in
CH2Cl2 at room temperature to afford 81% of the 1-adamantanyl
thiosialoside 5 (Scheme 2).11 Donor 2 then was derived from 5
in quantitative yield by treatment with isopropenyl acetate
catalyzed by CSA at 65 °C (Scheme 2).
TABLE 1. Sialylation of 1-Octanol with 1 and 2
SCHEME 2. Synthesis of Donor 2
entry
donor
solvent
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
MeCN
CH2Cl2/MeCN(1/1)
EtCN
T (°C)
yielda (%)
R/âb
1
2
3
4
5c
6
7
2
10
2
2
10
2
-40
-40
-78
-40
-40
-78
-78
89
73
92
89
1/8
1/4
1/2.5
1.6/1
88
81
2/1
2.2/1
2
a Isolated yields. b Determined by 1H NMR analysis of the crude reaction
mixture. c No activation observed.
The preparation of donor 3 started with 5 (Scheme 3), to
which a N-Boc group was introduced with Boc2O in the
presence of DMAP to give 6. Deacetylation of 6 with NaOMe
in MeOH at room temperature then gave 7. The N-Boc group
in 7 was cleanly cleaved by TFA to afford the intermediate
8,12 which was then transformed into the 5-N,4-O-carbonyl-
protected derivative 9 by treatment with 4-nitrophenyl chloro-
formate and NaHCO3 in H2O/MeCN. The hydroxyl groups in
9 were acetylated with Ac2O and pyridine at room temperature,
and then the nitrogen in the oxazolidinone was acetylated with
AcCl and EtN(i-Pr)2 in a one pot procedure to afford the donor
3 in 90% yield.
with NIS/TfOH, when it gave improved R-selectivity (Table 1,
entry 3). When the solvent was changed to acetonitrile, the
coupling reaction of 2 was achieved at -40 °C with the ratio
being changed in favor of the R-anomeric product by the nitrile
effect (Table 1, entry 4). Under the same conditions, activation
of the phenyl thiosialoside 10 could not be achieved (Table 1,
entry 5). The R-selectivity of the sialylation with 2 could be
further improved when the reaction was performed at -78 °C
using CH2Cl2/MeCN (1/1) or propionitrile as solvents (Table
1, entries 6 and 7). These results showed the 1-adamantanyl
thiosialoside 2 to be a more reactive sialyl donor than the
phenylthio derivative 10 in both CH2Cl2 and nitrile solvents at
low temperatures. Moreover, use of the “nitrile effect” improved
the R-selectivity, albeit to a limited extent.
SCHEME 3. Synthesis of Donor 3
Next, the N-acetyl-5-N,4-O-oxazolidinone-protected adaman-
tanyl thiosialoside 3 was tested in couplings to a series of
primary acceptors in CH2Cl2/MeCN (1/1) at -78 °C under NIS/
TfOH promotion conditions (Table 2, entries 1-4).13 The yields
and selectivities of these reactions were excellent and compa-
rable to those from the corresponding sialylations with N-acetyl-
5-N,4-O-oxazolidinone-protected phenyl thiosialoside donor 1
promoted with NIS/TfOH in CH2Cl2 at -40 °C.3
Most importantly, donor 3 was found to be superior to 1 in
couplings to sterically hindered acceptors. Thus, coupling of 3
and 1-adamantanol under NIS/TfOH promotion conditions in
CH2Cl2/MeCN (1/1) at -78 °C gave the R-anomeric product
in excellent yield, with only a trace amount of the â-anomer
1
detected by H NMR analysis of the crude reaction mixture
(Table 2, entry 5). In the regioselective 3-OH sialylation of 16,
a much improved R-selectivity was obtained (Table 2, entry
6).14,15 In the sialylation of a more sterically hindered 3-OH
acceptor 17, the R-Neu5Ac(2f3)Gal disaccharide was obtained
as the major product (Table 2, entry 7). Presumably, the
enhanced R-selectivities observed can be attributed to the nitrile
effect as well as to the use of the reactive 1-adamantanylthio
The N,N-diacetyl protected adamantanyl thiosialoside donor
2 was first coupled to 1-octanol under NIS/TfOH promotion
conditions in CH2Cl2 at -40 °C (Table 1, entry 1). In this
glycosylation, donor 2 gave a higher glycosylation yield than
its phenylthio counterpart 10 but still afforded the â-coupling
product predominantly (Table 1, entries 1 and 2). It was then
found that donor 2 could be activated at -78 °C in CH2Cl2
(10) Marra, A.; Sinay¨, P. Carbohydr. Res. 1989, 190, 317.
(13) Although the results from Table 1 indicated that the use of pure
priopionitrile gave better results than the 1/1 mixture of acetonitrile and
dichloromethane, the latter system was selected for further investigation
because of its generally better solubilizing properties, especially at
(11) The â/R ratio of adamantanyl thioglycosides in the crude reaction
mixture was 6.6:1. As it had been previously demonstrated with 1 that
stereoselectivity was independent of anomeric configuration in the donor,3
no attempt was made to isolate the R-anomer of 5.
o
-78 C.
(12) The direct method for the removal of the N-acetyl group, heating
with MeSO3H in MeOH, gave lower yields of 8 and was attended by the
formation of the glycal resulting from elimination of the adamantanylthio
group. For application of the MeSO3H method see ref 4a and: (a) Sugata,
T.; Higuchi, R. Tetrahedron Lett. 1996, 37, 2613. (b) De Meo, C.;
Demchenko, A. V.; Boons, G. J. J. Org. Chem. 2001, 66, 5490.
(14) The formation of the regioisomeric products arising from glycosy-
lation at the 4-OH of acceptor 16 was not observed.
(15) The increased selectivity observed with 16 as compared to its 4-O-
benzyl analogue 17 (see Table 2, entries 6 and 7 and Table 3, entry 4 and
Table 4, entry 2) is noteworthy and presumably reflects the increased steric
bulk of 17.
J. Org. Chem, Vol. 72, No. 20, 2007 7795

TABLE 2. Sialylation of Primary and Sterically Hindered
Acceptors with 3
TABLE 4. Sialylation of 15 and 16 with 3 under Optimized
Conditions
a Isolated yields. b Determined by 1H NMR analysis of the crude reaction
mixture. c Coupled to the 3-OH.
further increase of the proportion of MeCN in the solvent to
1/1 led to a dropoff in R-selectivity, probably due to the
increased solvent polarity and the associated increased ionic
reaction character of the reaction (Table 3, entry 5).
When the MeCN/CH2Cl2 (1/2) solvent system was applied
to the sialylations of 1-adamantanol and 16 with donor 3,
improved R-selectivities were observed (Table 4, entries 1 and
2) compared to those obtained from the corresponding sialyla-
tions performed in MeCN/CH2Cl2 (1/1) (Table 3, entries 1 and
2).15
In conclusion, the 1-adamantanyl thiosialosides are shown
to have high reactivity under NIS/TfOH promotion conditions
in nitrile solvents at -78 °C. With the N-acetyl-5-N,4-O-
oxazolidinone-protected 1-adamantanylthio sialyl donor, both
Neu5Ac R-(2f6) Gal and Neu5Ac R-(2f3) Gal glycosidic
linkages can be installed efficiently with high yields and
R-selectivities.
a Isolated yields. b Determined by 1H NMR analysis of the crude reaction
mixture. c Coupled to the 3-OH.
TABLE 3. Effect of Nitrile Concentration on Sialylation of 17 with
3
Experimental Section
Methyl (1-Adamantanyl 5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-2-thio-D-glycero-â-D-galacto-non-2-ulopyranoside)-
onate (5). A mixture of 410 (2.23 g, 4.2 mmol), anhydrous CH2Cl2
(25 mL), 1-adamantanethiol (0.819 g, 4.6 mmol), and BF3‚OEt2
(1.3 mL, 10 mmol) was stirred overnight at room temperature under
N2 and then diluted with CH2Cl2 (500 mL), washed with saturated
aqueous NaHCO3, dried over Na2SO4, and concentrated under
reduced pressure. The residue was eluted from silica gel with
EtOAc/hexanes/2-propanol (10/10/1) to give 5 (2.20 g, 3.4 mmol,
81%): [R]20D ) -82 (c 1.0, CHCl3); 1H NMR (500 MHZ, CDCl3)
δ 5.46 (dd, J ) 2.0, 3.0 Hz, 1H), 5.42 (d, J ) 10.5 Hz, 1H), 5.30-
5.24 (m, 1H), 5.15 (td, J ) 1.5, 9.5 Hz, 1H), 5.01 (dd, J ) 2.0,
12.5 Hz, 1H), 4.54 (dd, J ) 3.0, 11.0 Hz, 1H), 4.20 (dd, J ) 9.0,
13.0 Hz, 1H), 4.06 (q, J ) 10.0 Hz, 1H), 3.82 (s, 3H), 2.53 (dd, J
) 5.0, 14.0 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.00-1.99 (m,
broad, 9H), 1.97-1.93 (m, broad, 4H), 1.85-1.84 (m, broad, 6H),
1.68-1.62 (m, broad, 6H); 13C NMR (125 MHz, CDCl3) δ 171.4,
170.9, 170.4, 170.2, 169.9 (C-1, 3JC-1, H-3ax ) 2.5 Hz), 86.2, 74.0,
72.8, 69.4, 69.0, 63.4, 52.9, 50.6, 49.6, 43.5, 40.0, 35.9, 29.8, 23.2,
21.2, 20.9, 20.8, 20.7; ESIHRMS calcd for C30H43N1O12S1Na ([M
+ Na]+) 664.23985, found 664.23858.
entry
solvent
CH2Cl2
MeCN/CH2Cl2
MeCN/CH2Cl2
MeCN/CH2Cl2
MeCN/CH2Cl2
solvent ratio
yielda (%) (R/â)b
1
2
3
4
5
83 (1/1.3)
85 (2.6/1)
87 (3.3/1)
89 (4/1)
1/10
1/5
1/2
1/1
85 (3/1)
a Isolated yields. b Determined by 1H NMR analysis of the crude reaction
mixture.
leaving group which permits activation at -78 °C. It is important
to note that all the sialylation reactions of 3 with both primary
and secondary acceptors were complete within 1 h and that the
coupling products could be easily isolated from the clean
reaction mixtures through simple chromatography on silica gel.
To probe the solvent effect further, a series of coupling
reactions of donor 3 with the secondary acceptor 17 were
conducted varying the proportions of MeCN and CH2Cl2 under
NIS/TfOH promotion conditions at -78 °C (Table 3). It was
found that a solvent mixture of 1/10 (V/V) MeCN and CH2Cl2,
containing approximately 80 equiv of MeCN was sufficient to
influence the selectivity (Table 3, entries 1 and 2). The best
R-selectivity was achieved when the proportion of MeCN in
the mixture was increased to 1/2 (v/v) (Table 3, entry 4). A
Methyl (1-Adamantanyl 5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-5-N-(1,1-dimethylethoxy)carbonyl-2-thio-D-glycero-
â-D-galacto-non-2-ulopyranoside)onate (6). To a solution of 5
(2.36 g, 3.7 mmol) in anhydrous THF (15 mL) were added di-tert-
butyl dicarbonate (8.04 g, 37 mmol) and DMAP (180 mg, 1.5
mmol) at room temperature. The mixture was stirred overnight at
60 °C under N2 before it was cooled to room temperature and
concentrated under reduced pressure. The residue was applied to
7796 J. Org. Chem., Vol. 72, No. 20, 2007

silica gel and eluted with hexanes/EtOAc (2/1) to give 6 (2.65 g,
temperature overnight, and concentrated under reduced pressure.
The residue was dissolved in anhydrous CH2Cl2, treated with EtN-
(i-Pr)2 (4.0 mL, 23 mmol, 10 equiv), and then cooled to 0 °C before
acetyl chloride (1.34 mL, 18.6 mmol, 8 equiv) was added. After
warming to room temperature, the resulting solution was poured
into saturated aqueous NaHCO3 solution, the organic layer was
separated, the aqueous layer was extracted twice with CH2Cl2, and
the combined organic phase was washed with brine, dried over Na2-
SO4, and concentrated under reduced pressure. The residue was
purified by chromatography on silica gel eluting with EtOAc/
1
3.6 mmol, 97%): [R]20 ) -50 (c 6.7, CHCl3); H NMR (500
D
MHZ, CDCl3) δ 5.59 (dt, J ) 4.5, 11.0 Hz, 1H), 5.31 (dd, J ) 2.0,
10.5 Hz, 1H), 5.28 (s, broad, 1H), 5.08 (d, J ) 9.0 Hz, 1H), 4.92
(d, J ) 12.5 Hz, 1H), 4.70 (t, J ) 10.5 Hz, 1H), 4.17 (dd, J ) 9.0,
12.5 Hz, 1H), 3.78 (s, 3H), 2.57 (dd, J ) 5.0, 13.5 Hz, 1H), 2.29
(s, 3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.94 (s, 3H), 1.93 (s, broad,
6H), 1.87 (s, 3H), 1.83-1.80 (m, broad, 3H), 1.64 (s, broad, 9H),
1.60 (s, broad, 6H); 13C NMR (125 MHz, CDCl3) δ 173.8, 170.8,
170.4, 170.3, 170.0, 169.7, 152.0, 86.2, 85.1, 74.0, 71.9, 69.3, 66.2,
63.2, 53.1, 52.7, 50.5, 43.5, 41.5, 35.9, 29.7, 28.2, 26.6, 21.0, 20.8,
20.65, 20.63; ESIHRMS calcd for C35H51N1O14S1Na ([M + Na]+)
764.29228, found 764.29451.
hexanes (1/1) to give donor 3 (1.31 g, 90%): mp 144-145 °C
1
(EtOAc/hexanes); [R]20 ) -78 (c 0.4, CHCl3); H NMR (500
D
MHz, CDCl3) δ 5.69 (t, J ) 2.5 Hz, 1H), 5.29 (td, J ) 2.0, 8.5 Hz,
1H), 4.77-4.66 (m, 3H), 4.14 (dd, J ) 8.0, 12.0 Hz, 1H), 3.83 (s,
3H), 3.66 (dd, J ) 9.5, 11.5 Hz, 1H), 2.79 (dd, J ) 3.5, 13.0 Hz,
1H), 2.47 (s, 3H), 2.17 (t, J ) 13.0 Hz, 1H), 2.12 (s, 3H), 2.10 (s,
3H), 2.01 (s, 3H), 2.03-1.97 (m, broad, 6H), 1.88-1.86 (m, broad,
3H), 1.65 (m, broad, 6H); 13C NMR (125 MHz, CDCl3) δ 172.3,
171.0, 170.6, 169.7, 169.4, 153.7, 85.6, 75.1, 74.1, 73.4, 72.4, 63.3,
60.2, 53.0, 51.3, 43.6, 38.7, 35.9, 29.8, 24.8, 21.2. 20.8, 20.7;
ESIHRMS calcd for C29H39N1O12S1Na ([M + Na]+) 648.20855,
found 648.20983.
Methyl (1-Adamantanyl 5-N,4-O-carbonyl-3,5-dideoxy-2-thio-
D-glycero-â-D-galacto-non-2-ulopyranoside)onate (9). To a solu-
tion of 6 (2.65 g, 3.6 mmol) in methanol (10 mL) was added a
catalytic amount of sodium methoxide. The solution was stirred
for 1 h at room temperature and then quenched with Amberlyst 15
ion-exchange resin. The mixture was filtered through Celite and
concentrated under reduced pressure to give 7. The crude 7 was
treated with trifluoroacetic acid (8.0 mL) for 1 h at room
temperature, and then the mixture was concentrated under reduced
pressure. The concentrate and NaHCO3 (1.50 g, 17.8 mmol) were
dissolved in MeCN (15 mL) and H2O (30 mL) and cooled to 0 °C.
To the vigorously stirred mixture was slowly added 4-nitrophenyl
chloroformate (1.80 g, 8.9 mmol) in MeCN (15 mL) through a
dropping funnel, after which stirring was continued for 3 h at
0 °C. The resulting mixture was extracted with EtOAc (100 mL ×
3), and the combined extracts were washed with brine and then
dried over Na2SO4 and concentrated. The residue was purified by
silica gel column chromatography, eluting with EtOAc then EtOAc/
MeOH from 10/1 to 5/1 to give the title compound 9 as white foam
General Coupling Protocol. A solution of donor (0.11 mmol,
1.0 equiv), acceptor (0.16 mmol, 1.5 equiv), and activated 4 Å
powdered molecular sieves (216 mg, 2.0 g/mmol) in anhydrous
CH2Cl2/MeCN (1/1, 2 mL) was stirred for 1 h under Ar, and then
cooled to -40 °C (or -78 °C) followed by addition of NIS (58.3
mg, 0.26 mmol, 2.4 equiv) and TfOH (9.5 µL, 0.11 mmol, 1.0
equiv). The reaction mixture was stirred at -40 °C (or -78 °C)
for 1 h and then quenched with triethylamine (22.6 µL, 0.16 mmol,
1.5 equiv). The mixture was diluted with CH2Cl2, filtered through
Celite, washed with 20% aqueous Na2S2O3 solution, dried over Na2-
SO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel eluting with THF/
Hexanes system to afford coupling products, the spectra of which
were identical to those of authentic samples.3
(1.06 g, 2.3 mmol, 65% after three steps): [R]20 ) -162 (c 2.2,
D
MeOH); 1H NMR (500 MHz, MeOD) δ 4.59-4.54 (m, 1H), 4.50
(dd, J ) 2.0, 10.0 Hz, 1H), 3.84 (s, 3H), 3.83 (dd, J ) 2.5, 7.0 Hz,
1H), 3.75-3.68 (m, 2H), 3.57-3.51 (m, 2H), 2.68 (dd, J ) 4.0,
12.5 Hz, 1H), 2.26 (t, J ) 12.5 Hz, 1H), 2.04-1.96 (m, broad,
9H), 1.70 (s, broad, 6H); 13C NMR (125 MHz, MeOD) δ 172.0,
161.0, 86.1, 77.8, 73.8, 70.9, 70.2, 63.5, 58.4, 52.4, 50.2, 43.2, 39.1,
35.8, 30.0; ESIHRMS calcd for C21H31N1O8S1Na ([M + Na]+)
480.16629, found 480.16637.
Acknowledgment. We thank the NIH (GM 62160) for
financial support of this work.
Supporting Information Available: Full experimental details
for the preparation of 2 and copies of NMR spectra for all new
compounds and coupling products. This material is available free
of charge via the Internet at http://pubs.acs.org.
Methyl (1-Adamantanyl 5-acetamido-7,8,9-tri-O-acetyl-5-N,4-
O-carbonyl-3,5-dideoxy-2-thio-D-glycero-â-D-galacto-non-2-ul-
opyranoside)onate (3). A solution of 9 (1.06 g, 2.3 mmol) in
pyridine (20 mL) was treated with Ac2O (24 mL), stirred at room
JO7012912
J. Org. Chem, Vol. 72, No. 20, 2007 7797