Regioselective Acylation of Hexopyranosides with Pivaloyl Chloride

Full text of DOI:10.1021/jo980294v

J . Org. Chem. 1998, 63, 6035-6038
6035
Ta ble 1. Selective Acyla tion of Ca r boh yd r a tes w ith
Regioselective Acyla tion of
Hexop yr a n osid es w ith P iva loyl Ch lor id e
P iva loyl Ch lor id e in P yr id in e a t 0 °C
Lu J iang and Tak-Hang Chan*
Department of Chemistry, McGill University,
Montre´al, Que´bec H3A 2K6, Canada
Received February 18, 1998
Selective acylation of carbohydrates is one of the most
valuable reactions in carbohydrate synthesis.1 The most
widely studied is selective benzoylation. A number of
benzoylating reagents, such as benzoyl cyanide,2 benzoyl
imidazole,3 and 1-(benzoyloxy)benzotriazole4 in addition
to benzoyl chloride,5 have been examined. More recently,
activation through partial stannylation of carbohydrate
with (Bu3Sn)2O or Bu2SnO followed by electrophilic
attack with benzoyl chloride6 has been used. However,
the selectivity of benzoylation has not always been high,
and the separation of various regioisomers of benzoylated
carbohydrate derivatives, often by chromatography, can
be tedious. Selective acylation of carbohydrates with
pivaloyl chloride to give the corresponding pivaloyl ester
has been used, however, mainly as a selective method of
esterifying the primary hydroxy group in the presence
of secondary hydroxy groups.7 There have been few
systematic studies in the selective pivaloylation of sec-
ondary hydroxy groups in various mono- or oligosaccha-
rides. Treatment of methyl R-D-glucopyranoside (1) in
ether with pivaloyl chloride and pyridine at 4 °C gave
almost exclusively the 2,6-di-O-pivalate (2) (Table 1).8
Similarly, methyl 4,6-O-benzylidene-R-D-glucopyranoside
(3) gave the corresponding 2-O-pivalate 4 as the major
product. It thus appears that the 2-OH is the most
reactive among all the secondary hydroxy functions in
R-D-glucopyranosides. As far as we are aware, no inves-
tigation of pivaloylation of other monosaccharides has
been reported.9 Because the pivaloyl esters are usually
crystalline compounds and easily characterized by 1H
NMR spectroscopy, we became interested in the selective
esterification of other hexopyranosides.
Resu lts a n d Discu ssion
We found that the use of pivaloyl chloride in pyridine
is very effective in the selective acylation of carbohydrates
under mild conditions. As reported previously with ether
as the solvent, 1 was converted selectively to 2 in 83%
yield, and 3 to 4 in 79% yield. On the other hand,
treatment of methyl R-D-mannopyranoside (5) with piv-
aloyl chloride in pyridine gave selectively methyl 3,6-di-
O-pivaloyl-R-D-mannopyranoside (6) in 91% isolated yield
(1) Haines, A. H. Adv. Carbohydr. Chem. Biochem. 1981, 39, 11.
(2) Abbas, S. A.; Haines, A. H. Carbohydr. Res. 1975, 39, 358.
(3) Carey, F. A.; Hodgson, K. O. Carbohydr. Res. 1970, 12, 463.
(4) Kim, S.; Chang, H.; Kim, W. J . J . Org. Chem. 1985, 50, 1751.
(5) Williams, J . M.; Richardson, A. C. Tetrahedron 1967, 23, 1369.
(6) Ogawa, T.; Matsui, M. Tetrahedron 1981, 37, 2363.
(7) (a) Nucleosides: Robins, M. J .; Hawrelak, S. D.; Kanai, T.;
Siefert, J . M.; Mengel, R. J . Org. Chem. 1979, 44, 1317. (b) Lipoxins
B: Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 454. (c) Mannitol:
Angyal, S. J .; Evans, M. E. Aust. J . Chem. 1972, 25, 1495.
as a crystalline solid. Similarly, methyl 4,6-O-ben-
zylidene-R-D-mannopyranoside (7) was regioselectively
converted to methyl 3-O-pivaloyl-4,6-O-benzylidene-R-D-
mannopyranoside (8) in 89% yield. The higher reactivity
of the 3-OH group in mannopyranosides is not unex-
pected since the 2-OH is in the sterically hindered axial
(8) Tomic-Kulenovic, S.; Keglevic, D. Carbohydr. Res. 1980, 85, 302.
(9) For selective pivaloylation of sucrose, see: Hough, L.; Chowdhary,
M. S.; Richardson, A. C. J . Chem. Soc., Chem. Comm. 1978, 664.
S0022-3263(98)00294-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/31/1998

6036 J . Org. Chem., Vol. 63, No. 17, 1998
Notes
Sch em e 1a
position, and the 4-OH is generally known to be the least
reactive. On the other hand, treatment of phenyl 1-thio-
â-D-galactopyranoside (9) with pivalolyl chloride in py-
ridine at 0 °C gave the 3,6-di-O-pivalate 10 in 78% yield.
The selective acylation of 3-OH persisted in the reaction
of phenyl 4,6-O-benzylidene-1-thio-â-D-galactopyranoside
(11) under the same conditions. The 3-O-pivalate 12 was
obtained in 75% yield. The greater reactivity of the 3-OH
in the galactopyranosides is more difficult to explain. It
may be caused by the lower reactivity of the 2-OH which
is due to the presence of the â-substituent at the anomeric
position or the enhanced reactivity of the 3-OH due to
the presence of the adjacent axial function at the 4-posi-
tion. It is likely that the latter explanation is more
plausible.10 When the thiophenyl lactose pyranoside 13
was treated with pivaloyl chloride in pyridine, the 3′,6′,6-
tri-O-pivalate 14 was obtained in 73% yield. It is the
3′-OH with the adjacent axial function (at 4′-OH) rather
than the 3-OH that has been esterified selectively after
the primary hydroxyl groups. This is in agreement with
the observation that methyl R-D-galactopyranoside (15)
gave a 1:1 mixture of 3,6-di-O-pivalate 16 and 2,6-di-O-
pivalate 17 in 88% yield under the same pivaloylation
conditions. It may be due to the similar reactivities of
the 2- and 3-OH which are both adjacent to an axial
function at 1- and 4-positions. Finally, it should be noted
that it is not possible to selectively pivaloylate the
primary 6-OH over one of the secondary hydroxyl groups
in compouds 1, 5, 9, 13, and 15. This suggests that the
reactivity of a secondary hydroxyl group with an adjacent
axial function is as high as that of the primary 6-OH
group toward pivaloylation.10
a
Reagents and conditions: (i) 4.0 equiv of benzyl 2,2,2-trichlo-
roacetimidate, 0.05 equiv of CF3SO3H, 4:1 cyclohexane/CH2Cl2, rt,
4 h; (ii) KOH, CH3OH, reflux for 3 h; (iii) CH3COOH, (CH3CO)2O,
catalytic H2SO4, 4 h; (iv) 1.2 equiv of thiophenol, 0.8 equiv of
Me3SiOSO2CF3, 4 Å molecular sieves, CH2Cl2, 2 h.
acetic anhydride/acetic acid with sulfuric acid as a
catalyst to give the 1,3,6-tri-O-acetate 24.11b The ano-
meric acetate group in 24 can be exchanged with thiophe-
nol under acidic conditions to give the phenyl 3,6-di-O-
acetyl-2,4-di-O-benzyl-1-thio-R-D-mannopyranoside 25
which is an important glycosyl donor frequently used in
the synthesis of branched high mannans.
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR spectra were recorded at 500 and
125 MHz, respectively, and the chemical shifts are reported in
parts per million on the δ scale relative to internal TMS. The
site of pivaloylation is determined by 2D COSY 1H NMR
spectroscopy. Melting points are uncorrected. Solvents and
reagents were used as received from commercial sources.
Analytical thin-layer chromatography (TLC) was performed
using E. Merck silica gel 60 F-254 polyester-backed plates (250
µm thick). Benzylidene acetals were prepared according to the
known procedure.13
In the absence of the adjacent axial alkoxy group as
in the case of the phenyl 1-thio-â-D-glucopyranoside 20,
the compound can be selectively pivaloylated to afford
the 6-O-pivaloyl-â-D-glucopyranoside 21 in 77% yield
together with 10% of the 3,6-di-O-pivaloyl-â-D-glucopy-
ranoside 22. Furthermore, compound 22 can be obtained
in high yield (entry 11) from 21 under the same reaction
conditions. This tends to suggest that in the absence of
an adjacent axial function, the secondary 3-OH may be
more reactive than the secondary 2-OH toward pivaloy-
lation. Similarly, high selectivity was observed on the
pivaloylation of phenyl 4,6-O-benzylidene-1-thio-â-D-glu-
copyranoside (18) which gave the 3-O-pivalate 19 in 79%
yield.
Gen er a l P r oced u r e for th e P iva loyla tion . To a stirred
solution of the carbohydrate compound (10 mmol) in pyridine
(15 mL) at 0 °C was slowly added pivaloyl chloride (20-50
mmol). The reaction was monitored by TLC, and the addition
of pivaloyl chloride was stopped when the starting material or
the intermediate disappeared. The reaction mixture was then
diluted with ethyl acetate and washed with a dilute HCl solution,
a saturated NaHCO3 solution, and then brine. The organic
phase was dried over anhydrous MgSO4 and evaporated to
dryness. The crude product was subject to flash column chro-
matography (E. Merck silica gel 60, 230-400 mesh ASTM) using
hexanes and ethyl acetate (2:1, v/v) as an eluant to afford the
pure product. It can also be crystallized from the 10:1 (v/v)
mixture of hexanes and ethyl acetate with a slightly lower yield.
Meth yl 2,6-d i-O-p iva loyl-r-D-glu cop yr a n osid e (2):8 color-
These partially protected carbohydrates are very useful
intermediates for oligosaccharide synthesis. For ex-
ample, the mannose di-O-pivalate derivative 6 can be
used readily as a precursor for the synthesis of polyman-
nans (Scheme 1).11 Compound 6 was easily benzylated
with benzyl imidate under acidic conditions,12 and the
pivaloyl groups can be readily removed with KOH in CH3-
OH to give the 3,6-diol 23 which can serve as the glycosyl
acceptor in the synthesis of 3,6-branched polymannans.11a
Alternatively, compound 23 can undergo acetolysis with
less crystals; mp 84-85 °C (lit.8 mp 82-84 °C); [R]20 +87.7° (c
D
1.03, CHCl3); 1H NMR (500 MHz, CDCl3) δ 4.89 (1H, d, 3.7 Hz,
H-1), 4.60 (1H, dd, 3.7 and 10.0 Hz, H-2), 4.52 (1H, dd, 4.4 and
12.2 Hz, H-6a), 4.25 (1H, dd, 2.0 and 12.2 Hz, H-6b), 3.98 (1H,
dd, 9.5 and 9.5 Hz, H-3), 3.76 (1H, ddd, 2.2, 4.1, and 10.1 Hz,
H-5), 3.37 (3H, s, OCH3), 3.34 (1H, dd, 9.5 and 9.5 Hz, H-4),
3.06 [1H, s (br), OH], 2.41 [1H, s (br), OH], 1.24 [9H, s, COC-
(CH3)3]; 13C NMR (125 MHz, CDCl3) δ 179.4, 178.3, 96.9, 72.9,
71.2, 70.4, 69.4, 62.8, 55.3, 38.8, 38.7, 27.0, 26.9.
Met h yl 4,6-O-b en zylid en e-2-O-p iva loyl-r-D-glu cop yr a -
n osid e (4):8 colorless crystals; mp 150-152 °C (lit.8 mp 149-
151 °C); [R]20D +105° (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.50-7.37 (5H, m, Ar-H), 5.56 (1H, s, PhCH), 4.94 (1H, d, 3.7
Hz, H-1), 4.74 (1H, dd, 3.7 and 9.5 Hz, H-2), 4.30 (1H, dd, 4.6
and 10.3 Hz, H-6a), 4.20 (1H, dd, 9.5 and 9.5 Hz, H-3), 3.86 (1H,
ddd, 4.6, 9.9, and 10.0 Hz, H-5), 3.77 (1H, dd, 10.0 and 10.3 Hz,
(10) The origin of the selectivity is not clear. Since pivaloyl chloride
is relatively bulky, it is likely that the reagent would approach the
hydroxyl group from the side and not from the top or bottom of the
ring system. The reaction is therefore more subject to steric hindrance
of the adjacent equatorial substituents.
(11) (a) Ogawa, T.; Katano, K.; Sasajima, K.; Matsui, M. Tetrahedron
1981, 37, 2779. (b) Ogawa, T.; Sasajima, K. Tetrahedron 1981, 37, 2787.
(c) Merritt, J . R.; Naiseng, E.; Fraser-Reid, B. J . Org. Chem. 1994, 59,
4443.
(12) Iversen, T.; Bundle, K. R. J . Chem. Soc., Chem. Commun. 1981,
1240.
(13) Ferro, V.; Mocerino, M.; Stick, R. V.; Tilbrook, M. G. Aust. J .
Chem. 1988, 41, 813.

Notes
J . Org. Chem., Vol. 63, No. 17, 1998 6037
H-6b), 3.57 (1H, dd, 9.4 and 9.4 Hz, H-4), 3.39 (3H, s, OCH3),
2.31 [1H, s (br), C3-OH], 1.24 [9H, s, COC(CH3)3]; 13C NMR (125
MHz, CDCl3) δ 178.2, 137.0, 129.3, 128.3, 126.3, 102.0, 97.6, 81.3,
73.4, 68.9, 68.8, 62.0, 55.6, 38.9, 27.0.
sid e (17): colorless foam; Rf ) 0.30 (2:1 hexanes/EtOAc); 1H
NMR (500 MHz, CDCl3) δ 5.05 (1H, dd, 3.2 and 10.3 Hz), 4.93
(1H, dd, 3.7 and 10.0 Hz), 4.89 (1H, d, 3.7 Hz), 4.84 (1H, d, 3.9
Hz), 4.43 (1H, dd, 6.3 and 11.5 Hz), 4.33 (1H, dd, 5.4 and 11.5
Hz), 4.24 (1H, dd, 7.1 and 11.5 Hz), 4.20 (1H, dd, 6.6 and 11.5
Hz), 4.04-3.95 (5H, m), 3.92 [1H, dd (br), 3.2 and 3.4 Hz], 3.45
(3H, s, OCH3), 3.37 (3H, s, OCH3), 2.70 (1H, d, 3.7 Hz, OH), 2.56
(1H, d, 6.8 Hz, OH), 2.06 (1H, d, 1.9 Hz, OH), 1.88 (1H, d, 11.2
Hz, OH), 1.26 [9H, s, COC(CH3)3], 1.24 [9H, s, COC(CH3)3], 1.22
[9H, s, COC(CH3)3], 1.21 [9H, s, COC(CH3)3]; 13C NMR (125
MHz, CDCl3) δ 179.0, 178.7, 178.4, 178.3, 99.6, 97.4, 72.7, 71.4,
69.4, 68.3, 68.2, 68.0, 67.6, 67.3, 63.1, 63.0, 55.4 (2C), 39.0, 38.9,
38.8 (2C), 27.1 (2C), 27.0 (2C).
P h en yl 4,6-O-b en zylid en e-3-O-p iva loyl-1-t h io-â-D-glu -
cop yr a n osid e (19): colorless cryatals; Rf ) 0.51 (2:1 hexanes/
EtOAc); mp 131-132 °C; [R]20D -71.2° (c 0.68, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.56-7.33 (10H, m, Ar-H), 5.52 (1H, s,
PhCH), 5.19 (1H, dd, 9.1 and 9.5 Hz, H-3), 4.71 (1H, d, 9.8 Hz,
H-1), 4.40 (1H, dd, 5.0 and 10.6 Hz, H-6a), 3.79 (1H, dd, 10.3
and 10.3 Hz, H-6b), 3.66 (1H, dd, 9.5 and 9.5 Hz, H-4), 3.59-
3.54 (2H, m, H-2, H-5), 2.88 (1H, d, 2.9 Hz, C2-OH), 1.22 [9H, s,
COC(CH3)3]; 13C NMR (125 MHz, CDCl3) δ 178.9, 136.9, 133.0,
131.6, 129.1, 128.9, 128.4, 128.2, 125.9, 101.1, 89.6, 78.2, 75.0,
71.9, 70.7, 68.5, 39.0, 27.1; FAB HRMS calcd for C24H29O6S (M
+ H+) 445.1685, found 445.1686. Anal. Calcd for C24H28O6S:
C, 64.84; H, 6.35. Found: C, 64.83; H, 6.60.
P h en yl 6-O-p iva loyl-1-th io-â-D-glu cop yr a n osid e (21): col-
orless foam; Rf ) 0.20 (1:3 hexanes/EtOAc); [R]20D -32.5° (c 0.75,
CH3OH); 1H NMR (500 MHz, CDCl3) δ 7.50-7.18 (5H, m, Ar-
H), 4.58 (1H, d, 9.8 Hz, H-1), 4.48 [s (br), H2O], 4.43 (1H, dd, 1.8
and 12.1 Hz, H-6a), 4.14 (1H, dd, 6.9 and 12.1 Hz, H-6b), 3.56
(1H, dd, 8.8 and 9.0 Hz, H-3), 3.51 (1H, ddd, 1.8, 7.2, and 9.7
Hz, H-5), 3.37 (1H, dd, 9.3 and 9.3 Hz, H-2), 3.33 (1H, dd, 9.5
and 9.5 Hz, H-4), 1.16 [9H, s, COC(CH3)3]; 13C NMR (125 MHz,
CDCl3) δ 179.1, 132.8, 131.8, 128.9, 127.6, 87.6, 77.7, 77.6, 71.9,
70.1, 64.0, 38.8, 27.1; FAB HRMS calcd for C17H25O6S (M + H+)
357.1372, found 357.1370. Anal. Calcd for C17H24O6S‚H2O: C,
54.53; H, 7.00. Found: C, 54.89; H, 6.70.
Meth yl 3,6-d i-O-p iva loyl-r-D-m a n n op yr a n osid e (6): color-
less crystals; Rf ) 0.28 (2:1 hexanes/EtOAc); mp 93-94 °C; [R]20
D
+56.3° (c 0.71, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.04-5.01
(1H, m, H-3), 4.70 (1H, d, 1.7 Hz, H-1), 4.41-4.35 (2H, m, H-6a,
H-6b), 3.98 [1H, s (br), H-2], 3.81-3.75 (2H, m, H-4, H-5), 3.38
(3H, s, OCH3), 2.62 (1H, d, 2.2 Hz, C4-OH), 1.86 (1H, d, 2.9 Hz,
C2-OH), 1.23 [9H, s, COC(CH3)3], 1.22 [9H, s, COC(CH3)3]; 13C
NMR (125 MHz, CDCl3) δ 178.9, 178.8, 100.4, 74.2, 70.9, 69.4,
66.3, 63.2, 54.9, 39.0, 38.7, 27.2, 27.1; FAB HRMS calcd for
C17H31O8 (M + H+) 363.2019, found 363.2018. Anal. Calcd for
C17H30O8: C, 56.34; H, 8.34. Found: C, 56.72; H, 8.34.
Meth yl 4,6-O-ben zylid en e-3-O-p iva loyl-r-D-m a n n op yr a -
n osid e (8): colorless crystals; Rf ) 0.27 (2:1 hexanes/EtOAc);
mp 98-100 °C; [R]20D +28.9° (c 0.58, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.44-7.32 (5H, m, Ar-H), 5.57 (1H, s, PhCH), 5.33 (1H,
dd, 3.4 and 10.3 Hz, H-3), 4.76 (1H, d, 1.7 Hz, H-1), 4.30 (1H,
dd, 4.2 and 9.8 Hz, H-6a), 4.13 (1H, dd, 1.5 and 3.2 Hz, H-2),
4.10 (1H, dd, 9.3 and 10.3 Hz, H-4), 3.92 (1H, ddd, 4.4, 9.3, and
10.3 Hz, H-5), 3.85 (1H, dd, 10.0 and 10.3 Hz, H-6b), 3.41 (3H,
s, OCH3), 2.04 [1H, s (br), C2-OH], 1.23 [9H, s, COC(CH3)3]; 13
C
NMR (125 MHz, CDCl3) δ 177.2, 137.3, 128.8, 128.2, 125.9, 101.4,
101.3, 76.3, 70.4, 70.0, 68.9, 63.6, 55.1, 39.0, 27.2; FAB HRMS
calcd for C19H27O7 (M + H+) 367.1757, found 367.1755. Anal.
Calcd for C19H26O7: C, 62.27; H, 7.16. Found: C, 62.24; H, 7.25.
P h en yl 3,6-d i-O-p iva loyl-1-t h io-â-D-ga la ct op yr a n osid e
(10): colorless cryatals; Rf ) 0.38 (2:1 hexanes/EtOAc); mp 107-
108 °C; [R]20D +11.5° (c 0.75, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.57-7.31 (5H, m, Ar-H), 4.88 (1H, dd, 3.2 and 9.5 Hz, H-3),
4.61 (1H, d, 9.8 Hz, H-1), 4.35 (1H, dd, 5.5 and 11.6 Hz, H-6a),
4.28 (1H, dd, 6.8 and 11.6 Hz, H-6b), 4.01 [1H, s (br), H-4], 3.88
[1H, dd (br), 9.5 and 9.8 Hz, H-2], 3.80 [1H, dd (br), 6.1 and 6.1
Hz, H-5], 2.37 [1H, s (br), C2-OH], 2.06 [1H, s (br), C4-OH], 1.25
[9H, s, COC(CH3)3], 1.20 [9H, s, COC(CH3)3]; 13C NMR (125
MHz, CDCl3) δ 178.4, 178.0, 132.4, 132.3, 129.1, 128.1, 89.6, 76.2,
75.6, 67.6 (2C), 62.8, 39.1, 38.8, 27.2, 27.1; FAB HRMS calcd
for C22H33O7S (M + H+) 441.1947, found 441.1949. Anal. Calcd
for C22H32O7S: C, 59.97; H, 7.33. Found: C, 59.77; H, 7.54.
P h en yl 4,6-O-ben zylid en e-3-O-p iva loyl-1-th io-â-D-ga la c-
top yr a n osid e (12): colorless cryatals; Rf ) 0.36 (2:1 hexanes/
EtOAc); mp 178-179 °C; [R]20D +46.7° (c 0.61, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.67-7.20 (10H, m, Ar-H), 5.50 (1H, s,
PhCH), 4.86 (1H, dd, 3.5 and 9.6 Hz, H-3), 4.60 (1H, d, 9.5 Hz,
H-1), 4.40-4.37 (2H, m, H-4, H-6a), 4.05-4.01 (2H, m, H-6b,
H-2), 3.61 [1H, s (br), H-5], 2.29 (1H, d, 2.7 Hz, C2-OH), 1.19
[9H, s, COC(CH3)3]; 13C NMR (125 MHz, CDCl3) δ 178.4, 137.8,
133.0, 131.1, 129.0, 128.9, 128.1, 128.0, 126.1, 100.5, 88.0, 74.6,
73.4, 69.9, 69.2, 65.9, 39.0, 27.0; FAB HRMS calcd for C24H29O6S
P h en yl 3,6-di-O-pivaloyl-1-th io-â-D-glu copyr an oside (22):
colorless cryatals; Rf ) 0.36 (2:1 hexanes/EtOAc); mp 70-71 °C;
[R]20 -34.8° (c 0.56, CH3OH); 1H NMR (500 MHz, CDCl3) δ
D
7.59-7.29 (5H, m, Ar-H), 4.89 (1H, dd, 9.2 and 9.2 Hz, H-3),
4.58 (1H, d, 9.8 Hz, H-1), 4.43 (1H, dd, 2.3 and 12.1 Hz, H-6a),
4.34 (1H, dd, 5.5 and 12.1 Hz, H-6b), 3.59 (1H, ddd, 2.3, 5.5,
and 9.8 Hz, H-5), 3.46 (1H, dd, 9.4 and 9.4 Hz, H-2), 3.44 (1H,
dd, 9.5 and 9.5 Hz, H-4), 3.02 [1H, s (br), OH], 2.58 [1H, s (br),
OH], 1.24 [9H, s, COC(CH3)3], 1.22 [9H, s, COC(CH3)3]; 13C NMR
(125 MHz, CDCl3) δ 180.3, 178.8, 132.8, 131.7, 129.0, 128.2, 88.4,
79.0, 78.5, 70.4, 69.2, 63.4, 39.1, 38.9, 27.2, 27.1; FAB HRMS
calcd for C22H33O7S (M + H+) 441.1947, found 441.1949. Anal.
Calcd for C22H32O7S‚0.75H2O: C, 58.19; H, 7.44. Found: C,
58.31; H, 7.27.
(M + H+) 445.1685, found 445.1686. Anal. Calcd for C24H28
O6S: C, 64.84; H, 6.35. Found: C, 64.90; H, 6.29.
-
Meth yl 2,4-d i-O-ben zyl-r-D-m a n n op yr a n osid e (23):11a col-
1
P h en yl 4-(3′,6′-d i-O-p iva loyl-â-D-ga la ctop yr a n osyl)-6-O-
p iva loyl-1-th io-â-D-glu cop yr a n osid e (14): colorless crystals;
Rf ) 0.40 (1:2 hexanes/EtOAc); mp 101-103 °C; [R]20D +10.8° (c
0.58, CH3OH); 1H NMR (500 MHz, CDCl3) δ 7.57-7.27 (5H, m,
Ar-H), 4.83 (1H, dd, 3.3 and 10.1 Hz, H-3 Gal), 4.67 (1H, dd, 1.5
and 12.0 Hz, H-6a Glc), 4.58 (1H, d, 9.8 Hz, H-1 Glc), 4.38 (1H,
dd, 4.9 and 11.9 Hz, H-6a Gal), 4.35 (1H, d, 7.6 Hz, H-1 Gal),
4.23 (1H, dd, 7.3 and 11.7 Hz, H-6b Gal), 4.21 (1H, d, 1.5 Hz,
C3-OH Glc), 4.12 (1H, dd, 5.9 and 12.3 Hz, H-6b Glc), 3.99 [1H,
dd (br), 4.2 and 4.4 Hz, H-4 Gal], 3.92 (1H, ddd, 3.9, 7.8, and
10.3 Hz, H-2 Gal), 3.82 [1H, dd (br), 4.9 and 7.6 Hz, H-5 Gal],
3.64 (1H, ddd, 1.2, 8.6, and 8.8 Hz, H-3 Glc), 3.55 (1H, ddd, 1.5,
6.1, and 10.0 Hz, H-5 Glc), 3.39 (1H, ddd, 1.7, 8.8, and 9.8 Hz,
H-2 Glc), 3.32 [1H, s (br), C2-OH Gal], 3.31 (1H, dd, 8.4 and 9.8
Hz, H-4 Glc), 2.79 [1H, s (br), C2-OH Glc], 2.42 [1H, s (br), C4-
OH Gal], 1.25 [9H, s, COC(CH3)3], 1.20 [9H, s, COC(CH3)3], 1.19
[9H, s, COC(CH3)3]; 13C NMR (125 MHz, CDCl3) δ 178.8, 178.5,
178.0, 132.5, 132.2, 128.9, 128.0, 104.3, 87.2, 80.9, 77.3, 76.1,
74.2, 73.1, 71.6, 69.0, 67.2, 63.4, 62.8, 39.0, 38.9, 38.8, 27.2, 27.1,
27.0; FAB HRMS calcd for C33H50O13SNa (M + Na+) 709.2870,
found 709.2868. Anal. Calcd for C33H50O13S‚2H2O: C, 54.82;
H, 7.53. Found: C, 55.16; H, 7.68.
orless syrup; H NMR (500 MHz, CDCl3) δ 7.38-7.25 (10H, m,
Ar-H), 4.91 (1H, d, 11.2 Hz, PhCH2), 4.75 (1H, d, 1.7 Hz, H-1),
4.72 (1H, d, 11.7 Hz, PhCH2), 4.66 (1H, d, 11.2 Hz, PhCH2), 4.60
(1H, d, 11.7 Hz, PhCH2), 3.98 (1H, dd, 3.9 and 9.0 Hz, H-3), 3.86
(1H, dd, 2.9 and 11.7 Hz, H-6a), 3.79 (1H, dd, 4.4 and 11.7 Hz,
H-6b), 3.73 (1H, dd, 1.7 and 3.7 Hz, H-2), 3.67 (1H, dd, 9.5 and
9.5 Hz, H-4), 3.59 (1H, ddd, 2.9, 4.4, and 9.8 Hz, H-5), 3.31 (3H,
s, OCH3), 2.27 [1H, s (br), C2-OH], 1.93 [1H, s (br), C6-OH]; 13
C
NMR (125 MHz, CDCl3) δ 138.3, 137.6, 128.6, 128.5, 128.1, 128.0,
127.8, 127.7, 98.1, 78.3, 76.5, 74.9, 73.1, 71.7, 71.1, 62.3, 54.8.
1,3,6-Tr i-O-a cet yl-2,4-d i-O-b en zyl-r-D-m a n n op yr a n ose
(24):11a colorless syrup; 1H NMR (500 MHz, CDCl3) δ 7.36-7.25
(10H, m, Ar-H), 6.15 (1H, d, 2.2 Hz, H-1), 5.19 (1H, dd, 3.4 and
9.3 Hz, H-3), 4.71 (1H, d, 12.2 Hz, PhCH2), 4.69 (1H, d, 11.2 Hz,
PhCH2), 4.57 (1H, d, 11.2 Hz, PhCH2), 4.53 (1H, d, 12.2 Hz,
PhCH2), 4.31 (1H, dd, 2.2 and 12.2 Hz, H-6a), 4.27 (1H, dd, 4.4
and 12.2 Hz, H-6b), 3.99 (1H, dd, 9.5 and 9.8 Hz, H-4), 3.93 (1H,
ddd, 2.2, 4.4, and 9.8 Hz, H-5), 3.84 (1H, dd, 2.2 and 3.4 Hz,
H-2), 2.08 (3H, s, COCH3), 2.05 (3H, s, COCH3), 1.96 (3H, s,
COCH3).
P h en yl 3,6-d i-O-a cetyl-2,4-d i-O-ben zyl-1-th io-r-D-m a n -
n op yr a n osid e (25): colorless foam; Rf ) 0.42 (2:1 hexanes/
EtOAc); [R]20D +64.9° (c 0.50, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.47-7.25 (15H, m, Ar-H), 5.54 (1H, d, 2.0 Hz, H-1), 5.20 (1H,
Mixtu r e of m eth yl 3,6-d i-O-p iva loyl-r-D-ga la ctop yr a n o-
sid e (16) a n d m eth yl 2,6-d i-O-p iva loyl-r-D-ga la ctop yr a n o-

6038 J . Org. Chem., Vol. 63, No. 17, 1998
Notes
dd, 3.3 and 9.4 Hz, H-3), 4.71 (1H, d, 11.0 Hz, CH2Ph), 4.67 (1H,
d, 12.2 Hz, CH2Ph), 4.58 (1H, d, 11.2 Hz, CH2Ph), 4.48 (1H, d,
12.2 Hz, CH2Ph), 4.38 (1H, ddd, 3.2, 4.7, and 9.8 Hz, H-5), 4.34-
4.28 (2H, m, H-6a, H-6b), 4.11 (1H, dd, 2.0 and 3.2 Hz, H-2),
3.98 (1H, dd, 9.5 and 9.5 Hz, H-4), 2.02 (3H, s, COCH3), 1.98
(3H, s, COCH3); 13C NMR (125 MHz, CDCl3) δ 170.6, 170.0,
137.7, 137.4, 133.7, 131.8, 129.0, 128.5, 128.4, 127.9 (2C), 127.8,
127.7, 127.6, 85.1, 76.9, 74.7, 73.8, 73.5, 72.2, 70.6, 63.3, 20.9,
20.8; FAB HRMS calcd for C24H27O7 (MH+ - C6H6S) 427.1757,
found 427.1756. Anal. Calcd for C30H32O7S: C, 67.14; H, 6.01.
Found: C, 66.93; H, 5.91.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada and FCAR
of Quebec for financial support.
J O980294V