Asymmetric synthesis of methyl 6-deoxy-3-O-methyl-α-l-mannopyranoside from a non-carbohydrate precursor

Article abstract of DOI:10.1016/j.carres.2006.01.019

A novel method is reported for preparing methyl 6-deoxy-3-O-methyl-α- l-mannopyranoside (1) by asymmetric synthesis, using 2-acetylfuran (2), a non-chiral simple molecule, as the starting material and achieving high yields via (S)-1-(2-furyl)ethanol and (

Full text of DOI:10.1016/j.carres.2006.01.019

Carbohydrate Research 341 (2006) 725–729
Asymmetric synthesis of methyl 6-deoxy-3-O-methyl-
a-L-mannopyranoside from a non-carbohydrate precursor
Wenting Du and Yongzhou Hu*
ZJU-ENS Joint Laboratory of Medicinal Chemistry, School of Pharmaceutical Sciences, Zhejiang University,
Hubin campus, Hangzhou 310031, China
Received 17 May 2005; accepted 5 January 2006
Available online 3 February 2006
Abstract—A novel method is reported for preparing methyl 6-deoxy-3-O-methyl-a-L-mannopyranoside (1) by asymmetric synthesis,
using 2-acetylfuran (2), a non-chiral simple molecule, as the starting material and achieving high yields via (S)-1-(2-furyl)ethanol and
(S)-1-(2,5-dihydro-2,5-dimethoxy-2-furyl)ethanol.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Methyl 6-deoxy-3-O-methyl-a-L-mannopyranoside; 6-Deoxy-L-mannose; L-Rhamnose; (S)-1-(2-Furyl)ethanol; 2-Acetylfuran
1. Introduction
3-O-methyl-a-L-mannopyranose from
a
preformed
sugar, 3,4-di-O-acetyl-6-deoxy-L-glucal.7 Herein we report
a method for preparing methyl 6-deoxy-3-O-methyl-a-L-
mannopyranoside (1) by asymmetric synthesis, using
2-acetylfuran (2), a nonchiral simple molecule, as the
starting material, and most of the steps achieved high
yields.
6-Deoxy-L-mannose (L-rhamnose) derivatives occur natu-
rally in complex carbohydrates from many organisms:
in polysaccharides of the cell wall of prokaryotes,1 and
as building blocks of many natural products. Steroidal
glycoalkaloids isolated from many Solanum species have
6-deoxy-L-mannose as the sugar subunit.2 6-Deoxy-L-
mannose is found in lepidimoide, isolated from the exu-
date of germinated cress (Lepidium sativum L.) seeds and
serves as a potent novel allelopathic substance that pro-
motes the shoot growth of different plant species.3,4
Neuroprotective phenylpropanoid esters of 6-deoxy-L-
mannoses isolated from roots of Scrophularia buergeri-
ana may exert significant protective effects against gluta-
mate-induced neurode generation in primary cultures of
cortical neurons.5 Methyl 6-deoxy-3-O-methyl-a-L-
mannopyranoside (1), is a subunit of the antitumor anti-
biotic calicheamicin c1I .6,7 Various methods for synthesis
of 6-deoxy-L-mannose have been developed,7–9 but all
have started with preformed sugars. For example,
Halcomb et al. reported the synthesis of dimethylsilyl-
2. Results and discussion
The synthetic route for 6-deoxy-3-O-methyl-a-L-manno-
pyranoside (1) is depicted in Scheme 1. Asymmetric-
transfer hydrogenation of 2-acetylfuran (2) under
previously described conditions10 gave (S)-1-(2-furyl)-
ethanol (3). The (S)-furan alcohol 3 was oxidized to
(S)-1-(2,5-dihydro-2,5-dimethoxy-2-furyl)ethanol (4) by
use of bromine in methanol. Treatment of 4 with formic
acid under strictly anhydrous conditions gave a mixture
of the desired pyranosidulose 5 (61%) and its b anomer 6
(20%), which could be separated by flash chromato-
graphy. Both could be used in the synthesis of target
compound 1.
Reduction of ketone 5 with lithium aluminium
hydride or sodium borohydride proceeded with the
desired stereochemical result, giving 7 in high yield
*
Corresponding author. Fax: +86 571 87217412; e-mail: huyz@
zjuem.zju.edu.cn
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.01.019

726
W. Du, Y. Hu / Carbohydrate Research 341 (2006) 725–729
OMe
OMe
O
O
O
MeO
O
O
O
OH
OH
5
3
4
2
6β anomer
OMe
OMe
OMe
O
O
RO
RO
O
t-BuCOO
MeO
OH
HO
OH
7 R=H
8 R=COBu-t
10 R=COBu-t
R=H
9
1
Scheme 1.
(94%). The stereochemistry at OH-4 was determined to
be the desired orientation on the basis of the H-4, H-5
coupling constant (J4,5 8.6 Hz). At this point, the optical
purity of compound 7 was confirmed by 19F NMR com-
parison of its Mosher ester with the corresponding
material made from racemic 3. The 4-OH group of
allylic alcohol 7 was protected by t-BuCOCl to give
the pivaloyl ester 8 in 93% yield, and dihydroxylation
of 8 with OsO4, according to Halcomb’s method, pro-
duced diol 9 as the sole product,7 which could be selec-
tively and efficiently methylated (Bu2SnO, MeI) at OH-3
(9!10, 95%).11 Finally, mild basic hydrolysis of 10 gave
the target compound 1. The properties of compound 1
have been described.12
3. Experimental
3.1. General methods
Melting points were determined on a Kofler block appa-
ratus. Optical rotations were measured at 25 ꢁC with a
Perkin–Elmer 241/MS polarimeter at the sodium D line.
FTIR spectra were obtained for casts made by deposit-
ing the compound from solution on a KBr plate. 1H and
13C NMR spectra were recorded on a Bruker Avance
DMX spectrometer at 400 or 300 MHz using Me4Si as
the internal standard. Chemical shifts are expressed in
d (ppm). Mass spectra were recorded with an AEI
Model MS-50 mass spectrometer.
The ring-closure step from 4 afforded the b anomer 6
as a byproduct, but its stereochemistry could be
adjusted (Scheme 2). Reduction of ketone 6 with sodium
borohydride in THF afforded 11, and then pivaloyla-
tion of 11 gave 12 as the major product. This was
subjected without purification, to conditions for acetal
exchange with methanol in the presence of camphorsulf-
onic acid (CSA), so as to form mainly the a-glycal.
Finally, dihydroxylation with N-methylmorpholine
oxide (NMO) and OsO4 gave pure 9 in 75% overall yield
from 12.
3.2. (S)-1-(2-Furyl) ethanol (3)
A
mixture of [RuCl2 (g6-mesitylene)]2 (23 mg,
0.04 mmol), (1S,2S)-N-(p-tolylsulfonyl)-1,2-diphenyl-
ethylenediamine (29 mg, 0.08 mmol) and Et3N (22 lL,
0.16 mmol) in 2-propanol (0.8 mL) was stirred and
heated at 80 ꢁC for 1 h. The mixture was cooled to room
temperature, and evaporation of the solvent gave the
crude Ru(II) complex, which could be used in the next
step without further purification.
In summary, we have developed a novel method
to prepare methyl 6-deoxy-3-O-methyl-a-L-manno-
pyranoside, an important building block of caliche-
amicin cI1; starting not from a preformed sugar but
from a nonchiral simple compound. This method also
offers additional possibilities for incorporating isotopic
labels.
2-Acetylfuran (1.15 g, 10.44 mmol) was added to a
stirred mixture of the foregoing Ru(II) complex in an
anhydrous mixture of formic acid (3.8 mL) and Et3N
(1.5 mL), and stirring was continued at room tempera-
ture for 42 h. The mixture was cooled to 0 ꢁC, made
neutralized with saturated aq NaHCO3, extracted with
ether (2 · 20 mL), and the extract washed with brine
(10 mL). The combined organic layer was dried
(Na2SO4), and evaporated. The residue was purified by
flash chromatography (silica gel, 1:3 EtOAc–hexane)
to afford 3 (1.00 g, 85%, ee = 99%) as an analytically
O
O
OMe
OMe
RO
9
O
25
pure oil; ½aꢀD ꢁ23.42 (c 1.08, EtOH); FTIR (CH2Cl2
cast): 3355, 2980, 1149, 1068, 1009, 737 cmꢁ1 1H
;
6
11 R=H
12 R=COBu-t
NMR (CDCl3): d 1.54 (d, 3H, J 6.5 Hz), 1.98 (br, 1H),
4.88 (q, 1H, J 6.5 Hz), 6.23 (d, 1H, J 3.2 Hz), 6.33 (dd,
Scheme 2.

W. Du, Y. Hu / Carbohydrate Research 341 (2006) 725–729
727
1H, J 3.0, 1.9 Hz), 7.37 (d, 1H, J 1.3 Hz); 13C NMR
(CDCl3): d 21.13 (q0), 63.36 (d0), 104.96 (d0), 110.00
(d0), 141.67 (d0), 157.65 (s0).
of 5 (180 mg, 1.26 mmol) in THF (0.4 mL) was added
dropwise over 5 min, and stirring was continued for an
additional 5 min. The mixture was quenched with satu-
rated aq NH4Cl (2.0 mL), extracted with ether
(3 · 10 mL) and washed with brine (5.0 mL). The com-
bined organic layer was dried (Na2SO4), and evaporated.
The residue was purified by flash chromatography (silica
gel, 1:6 EtOAc–hexane) to afford 7 (163 mg, 90%) as an
3.3. (S)-1-(2,5-Dihydro-2,5-dimethoxy-2-furyl)ethanol (4)
A solution of 3 (1.52 g, 13.56 mmol) in a mixture of
MeOH (5.4 mL) and ether (3.8 mL) was stirred and
cooled to ꢁ40 ꢁC. Br2 (0.718 mL, 13.98 mmol) in
dry MeOH (5.4 mL) was added dropwise over 20 min.
After addition, stirring was continued for an additional
10 min. The mixture was saturated with NH3 to pH 8,
allowed to warm to room temperature, diluted with
ether and evaporated. The residue was purified by flash
chromatography (neutral alumina, 1:4 EtOAc–hexane)
to afford 4 (2.11 g, 89%) as a pure mixture of isomers;
1H NMR (CDCl3): d 1.13 (m, 3H), 2.24 (br, 1H),
3.16–3.53 (m, 6H), 3.85 (m, 1H), 5.45 (dt 1H, J 20.0,
1.2 Hz), 5.95 (m, 1H), 6.13 (m, 1H); Exact mass m/z calcd
for C8H13O3 (M+ꢁOH): 157.08647; found: 157.08680.
25
analytically pure oil; ½aꢀD ꢁ105.1 (c 1.1, CHCl3); FTIR
(CH2Cl2 cast): 3419, 2893, 1399, 1189, 1146, 1103,
1
1055, 963 cmꢁ1; H NMR (CDCl3): d 1.33 (d, 3H, J
5.7 Hz), 1.60 (br, 1H), 3.43 (s, 3H), 3.69 (m, 1H), 3.84
(t, 1H, J 8.6 Hz, H-4), 4.83 (d, 1H, J 1.5 Hz, H-1), 5.75
(dq, 1H, J 10.2, 2.5 Hz), 5.93 (dd, 1H, J 10.2, 0.7 Hz);
13C NMR (CDCl3): d 17.97 (q0), 55.62 (q0), 68.00 (d0),
69.64 (d0), 95.35 (d0), 126.43 (d0), 133.67 (d0); Exact mass
m/z calcd for C7H11O2 (M+ꢁOH): 127.075895; found:
127.07577.
Method B. A mixture of 5 (153 mg, 1.08 mmol) in
ether (6.0 mL) was stirred and cooled to ꢁ50 ꢁC. Lith-
ium aluminium hydride (41 mg, 1.08 mmol) was added
and stirring was continued for 45 min at this tempera-
ture. Potassium fluoride (100 mg) and water (0.1 mL)
were then added and the mixture was allowed to warm
to room temperature. The mixture was filtered over Cel-
ite (0.5 · 2 cm), and the pad was washed with ether. The
filtrate was concentrated under reduced pressure and
purified by flash chromatography (silica gel, 1:6
EtOAc–hexane) to afford 7 (147 mg, 94%) as an analy-
tically pure oil.
3.4. Methyl 2,3,6-trideoxy-a-L-glycero-hex-2-enopyano-
sid-4-ulose (5) and methyl 2,3,6-trideoxy-b-L-glycero-hex-
2-enopyranosid-4-ulose (6)
A solution of 4 (810 mg, 4.65 mmol) in MeOH (0.35 mL)
was added dropwise over 10 min to a stirred mixture of
anhydrous formic acid (3.5 mL) and MeOH (0.2 mL)
at room temperature. Stirring was continued for an addi-
tional 5 min. Water (8.0 mL) was added, and the mixture
was extracted with CHCl3 (3 · 15 mL), and washed with
saturated aq NaHCO3 (10.0 mL) and brine (10.0 mL).
The combined organic layer was dried (Na2SO4) and
evaporated. The residue was purified by flash chroma-
tography (silica gel, EtOAc–hexane, 2:98 to 1:20) to
afford the a anomer 5 (403 mg, 61%) as an analytically
3.6. Methyl 4-O-pivaloyl-2,3,6-trideoxy-a-L-erythro-hex-
2-enopyranoside (8)
A solution of 7 (130 mg, 0.90 mmol), pyridine (0.29 mL,
3.61 mmol) and DMAP (33.0 mg, 0.27 mmol) in CH2Cl2
(2.5 mL) was stirred and cooled to 0 ꢁC. t-BuCOCl
(0.22 mL, 1.80 mmol) was added dropwise. After the
addition, the mixture was allowed to warm to room tem-
perature and stirring was continued overnight (ꢂ12 h).
The mixture was quenched with saturated aq NaHCO3
(1.0 mL), extracted with ether (15 mL · 2) and washed
with brine (5.0 mL). The combined organic layer was
dried (Na2SO4), filtered and evaporated. The residue
was purified by flash chromatography (silica gel, 2:98
EtOAc–hexane) to afford 8 (192 mg, 93%) as an analy-
25
pure white solid; mp 55–56 ꢁC; ½aꢀD ꢁ14.5 (c 1.04,
CHCl3); FTIR (CH2Cl2 cast): 2939, 1700, 1374, 1231,
1
1104, 1088, 1048 cmꢁ1; H NMR (CDCl3): d 1.39 (d,
3H, J 6.7 Hz), 3.52 (s, 3H), 4.54 (q, 1H, J 6.8 HZ), 5.08
(d, 1H, J 3.5 Hz, H-1), 6.07 (d, 1H, J 10.2 Hz), 6.83
(dd, 1H, J 10.2, 3.4 Hz); 13C NMR (CDCl3): d 15.28
(q0), 56.54 (q0), 70.30 (d0), 94.22 (d0), 127.36 (d0), 143.30
(d0), 196.95 (s0).
The b anomer 6 (129 mg, 20%) was also obtained by
25
chromatography as an analytically pure oil; ½aꢀD +41.4
25
(c 1.3, CHCl3); 1H NMR (CDCl3): d 1.48 (d, 3H, J
6.8 Hz), 3.55 (s, 3H), 4.22 (q, 1H, J 6.8 Hz), 5.24 (dd,
1H, J 2.5, 1.7 Hz, H-1), 6.13 (dd, 1H, J 10.3, 1.5 Hz),
6.88 (dd, 1H, J 10.3, 1.9 Hz).
tically pure oil; ½aꢀD ꢁ167.4 (c 1.1, CHCl3); FTIR
(CH2Cl2 cast): 2978, 2934, 1733, 1398, 1275, 1156,
1
1082, 1057, 1037 cmꢁ1; H NMR (CDCl3): d 1.19 (s,
9H), 1.21 (d, 3H, J 6.3 Hz), 3.44 (s, 3H), 3.57 (dq, 1H,
J 9.2, 6.3 Hz), 4.86 (d, 1H, J 1.5 Hz, H-1), 5.04 (ddd,
1H, J 9.2, 1.1, 1.1 Hz, H-4), 5.76–5.84 (m, 2H); 13C
NMR (CDCl3): d 17.87 (q0), 26.98 (q0), 38.74 (s0),
55.67 (q0), 64.79 (d0), 70.46 (d0), 95.42 (d0), 127.42 (d0),
129.97 (d0), 177.83 (s0); Exact mass m/z calcd
C11H17O3 (M+ꢁOMe): 197.117755; found: 197.117795.
3.5. Methyl 2,3,6-trideoxy-a-L-erythro-hex-2-eno-
pyranoside (7)
Method A. A mixture of NaBH4 (24 mg, 0.63 mmol) in
water (1.8 mL) was stirred and cooled to 0 ꢁC. A solution

728
W. Du, Y. Hu / Carbohydrate Research 341 (2006) 725–729
3.7. Methyl 6-deoxy-4-O-pivaloyl-a-L-mannopyranoside
(9)
3.9. Methyl 6-deoxy-3-O-methyl-a-L-mannopyranoside
(1)
Osmium tetraoxide (2.5% w/v in t-BuOH, 150 lL,
0.015 mmol) was added to a stirred mixture of 8
(171 mg, 0.75 mmol) and NMO (97 mg, 0.83 mmol) in
9:1 acetone–water (1.7 mL) at room temperature. Stir-
ring was continued for 22 h, and the mixture was
quenched with 10% aq NaHSO3 (1.0 mL), extracted
with EtOAc (3 · 10 mL), and washed with 10% aq NaH-
SO3 (2.0 mL) and brine (5.0 mL). The combined organic
layer was dried (Na2SO4), and evaporated. The residue
was purified by flash chromatography (silica gel, 2:3
EtOAc–hexane) to afford 9 (191 mg, 97%) as an analy-
Lithium hydroxide monohydrate (102 mg, 2.43 mmol)
was added to a stirred solution of 10 (103 mg,
0.37 mmol) in a mixture of MeOH (13.6 mL) and water
(3.4 mL). The mixture was stirred at room temperature
for 5 days, then acidified with 10:1 MeOH–AcOH to
pH ꢂ 5–6, and concentrated under reduced pressure.
The residue was purified by flash chromatography (silica
gel, 2:1 EtOAc–hexane) to afford recovered 10 (11 mg)
and 1 (62 mg, 85%, not corrected for recovered 10) as
25
an analytically pure oil; ½aꢀD ꢁ65.5 (c 1.0, CHCl3);
lit.13–15 ꢁ51.1ꢁ, ꢁ61ꢁ (CHCl3), ꢁ60ꢁ (CHCl3); FTIR
25
tically pure white solid; mp 81–83 ꢁC; ½aꢀD ꢁ90.2 (c 1.07,
(CH2Cl2 cast): 3442, 2934, 2908, 113, 1118, 1078, 1057,
1
CHCl3); FTIR (CH2Cl2 cast): 3449, 2978, 2936, 1734,
982 cmꢁ1; H NMR (CDCl3): d 1.32 (d, 3H, J 6.2 Hz),
1187, 1158, 1101, 1067, 1039, 1013, 973 cmꢁ1
;
1H
2.31 (br s, 2H), 3.37 (dd, 1H, J 9.1, 3.3 Hz), 3.37 (s,
3H), 3.46 (s, 3H), 3.50 (t, 1H, J 9.3 Hz), 3.56 (dq, 1H,
J 10.2, 6.2 Hz), 4.05 (dd, 1H, J 3.1, 1.6 Hz), 4.72 (d,
NMR (CDCl3): d 1.18 (d, 3H, J 6.3 Hz), 1.2 (s, 9H),
3.15 (br, 2H), 3.36 (s, 3H), 3.76 (dq, 1H, J 9.2,
6.2 Hz), 3.81 (dd, 1H, J 9.6, 3.5 Hz), 3.91 (dd, 1H, J
3.5, 1.6 Hz), 4.69 (d, 1H, J 1.5 Hz, H-1), 4.77 (t, 1H, J
13
1H J 1.5 Hz, H-1); C (CDCl3) d 17.64 (q0), 54.93
(q0), 56.97 (q0), 66.77 (d0), 67.97 (d0), 71.59 (d0), 81.35
(d0), 100.47 (d0); Exact mass m/z calcd for C8H15O4
(M+ꢁOH): 175.097015; found: 175.097019.
13
9.6 Hz); C NMR (CDCl3): d 17.43 (q0), 27.08 (q0),
39.00 (s0), 55.07 (q0), 65.46 (d0), 70.44 (d0), 70.87 (d0),
75.32 (d0), 100.53 (d0), 179.74 (s0); Exact mass m/z calcd
C11H19O5 (M+ꢁOMe): 231.12325; found: 231.12353.
3.10. Methyl 4-O-pivaloyl-2,3,6-trideoxy-b-L-erythro-
hex-2-enopyranoside (12)
3.8. Methyl 6-deoxy-3-O-methyl-4-O-pivaloyl-a-L-
mannopyranoside (10)
A solution of sodium borohydride (19 mg, 0.50 mmol)
in water (1.4 mL) was stirred and cooled to 0 ꢁC. A solu-
tion of 6 (143 mg, 1.00 mmol) in THF (0.3 mL) was
added dropwise, and stirring was continued for 5 min.
The mixture was quenched with saturated aq NH4Cl
(1.0 mL), extracted with ether (3 · 10 mL) and washed
with brine (2.0 mL). The combined organic layer was
dried (Na2SO4), and evaporated. The resulting crude
alcohol was used directly in the next step.
A mixture of 9 (181 mg, 0.69 mmol) and Bu2SnO
(206 mg, 0.83 mmol) in a mixture of MeOH (3.0 mL)
and benzene (0.3 mL) was refluxed until all of the
Bu2SnO had dissolved and the solution became clear.
The mixture was diluted with benzene (2.5 mL) and con-
centrated under reduced pressure. Methyl iodide
(1.5 mL) was added to the residue, and the mixture
was stirred for 17 h at 45 ꢁC. The mixture was concen-
trated and the residue was diluted with saturated aq
NH4Cl (3.0 mL). The mixture was stirred at room tem-
perature for 30 min, extracted with EtOAc (3 · 10 mL)
and the extract washed with brine (10.0 mL). The com-
bined organic layer was dried (Na2SO4) and evaporated.
The residue was purified by flash chromatography (silica
gel, 1:4 EtOAc–hexane) to afford 10 (181 mg, 95%) as an
A solution of the foregoing crude alcohol 11, pyridine
(0.3 mL, 3.61 mmol) and DMAP (30 mg, 0.26 mmol)
in CH2Cl2 (2.5 mL) was stirred and cooled to 0 ꢁC and
t-BuCOCl (0.22 mL, 1.80 mmol) was added dropwise.
After the addition, the mixture was allowed to warm
to room temperature and stirring was continued over-
night (ꢂ12 h). The mixture was quenched with saturated
aq NaHCO3 (2.0 mL), extracted with ether (2 · 15 mL)
and washed with brine (5.0 mL). The combined organic
layer was dried (Na2SO4) and evaporated. The residue
was purified by flash chromatography (silica gel, 2:98
EtOAc–hexane) to afford 12 (152 mg, 66%) as an analyt-
ically pure oil and the C-4 epimer (50.7 mg, 22%), also
25
analytically pure white solid; mp 80–81 ꢁC; ½aꢀD ꢁ66.6 (c
1.1, CHCl3); FTIR (CH2Cl2 cast): 3467, 2979, 2935,
1736, 1280, 1155, 1135, 1117, 1087, 1059 cmꢁ1 1H
;
NMR (CDCl3): d 1.17 (d, 3H, J 6.3 Hz), 1.22 (s, 9H),
2.46 (br, 1H), 3.38 (s, 3H), 3.39 (s, 3H), 3.48 (dd, 1H,
J 9.5, 3.4 Hz), 3.76 (dq, 1H, J 9.2, 6.3 Hz), 4.06 (dd,
1H, J 2.5, 1.7 Hz), 4.76 (d, 1H, J 1.5 Hz, H-1), 4.98 (t,
25
as an analytically pure oil; Compound 12 had: ½aꢀD
ꢁ117.9 (c 1.05, CHCl3); FTIR (CH2Cl2 cast): 2977,
13
1H, J 9.7 Hz); C NMR (CDCl3): d 17.20 (q0), 27.00
2935, 1728, 1396, 1281, 1152, 1112, 1098, 1062,
1
(q0), 38.74 (s0), 54.93 (q0), 57.44 (q0), 65.88 (d0), 67.37
(d0), 71.86 (d0), 79.12 (d0), 100.70 (d0), 177.49 (s0); Exact
mass m/z calcd C12H21O5 (M+ꢁMe): 245.138875;
found: 245.138847.
1038 cmꢁ1; H NMR (CDCl3): d 1.20 (s, 9H), 1.29 (d,
3H, J 6.4 Hz), 3.46 (s, 3H), 3.81 (q, 1H, J 6.6 Hz),
5.04 (dq, 1H, J 6.9, 2.1 Hz, H-4), 5.08 (d, 1H, J
1.5 Hz, H-1), 5.82–5.87 (m, 2H); 13C NMR (CDCl3.):

W. Du, Y. Hu / Carbohydrate Research 341 (2006) 725–729
729
d 18.42 (q0), 38.77 (s0), 54.90 (q0), 69.57 (d0), 71.40 (d0),
References
97.28 (d0), 128.78 (d0), 129.96 (d0), 177.93 (s0); Exact
mass m/z calcd C11H17O3 (M+ꢁOMe): 197.117755;
found: 197.117795.
1. Tonetti, M.; Sturla, L.; Bisso, A.; Zanardi, D.; Benatti, U.;
Flora, A. D. Biochimie 1998, 80, 923–931.
2. Morillo, M.; Lequart, V.; Grand, E.; Goethals, G.;
Usubillaga, A.; Villa, P.; Martin, P. Carbohydr. Res.
2001, 334, 281–287.
3.11. Methyl 6-deoxy-4-O-pivaloyl-a-L-mannopyranoside
(9)
3. Hirose, K.; Endo, K.; Hasegawa, K. Carbohydr. Res.
2004, 339, 9–19.
4. Hirose, K.; Kosuge, Y.; Otomatsu, T.; Endo, K.; Hase-
gawa, K. Tetrahedron Lett. 2003, 44, 2171–2173.
5. Kim, S. R.; Kim, Y. C. Phytochemistry 2000, 54, 503–509.
6. Smith, A. L.; Pitsinos, E. N.; Hwang, C. K.; Mizuno, Y.;
Saimoto, H.; Scarlato, G. R.; Suzuki, T.; Nicolaou, K. C.
J. Am. Chem. Soc. 1993, 115, 7612–7624.
7. Halcomb, R. L.; Boyer, S. H.; Wittman, M. D.; Olson, S.
H.; Denhart, D. J.; Liu, K. K. C.; Danishefsky, S. J.
J. Am. Chem. Soc. 1995, 117, 5720–5749.
8. Johann, M.; Rapp, K. M.; Kelkheim, V. M. Biotechnol.
Adv. 1997, 15, 545.
9. Sammes, P. G.; Thetford, D. J. Chem. Soc., Perkin Trans.
1 1988, 111–123.
Camphorsulfonic acid (15 mg, 0.06 mmol) was added to
a stirred solution of 12 (110 mg, 0.48 mmol) in MeOH
(4.0 mL), and stirring was continued at room tempera-
ture for 4 h. The solution was concentrated, and satu-
rated aq NaHSO3 (1.0 mL) was added. The mixture
was extracted with ether (2 · 15 mL), and the extract
washed with water (4.0 mL) and brine (4.0 mL). The
combined organic layer was dried (Na2SO4) and evapo-
rated. The crude material was used immediately in the
next step.
N-Methylmorpholine oxide (57 mg, 0.48 mmol) and
OsO4 (2.5% w/v in t-BuOH, 97 lL, 0.0097 mmol) were
added to a stirred solution of the foregoing crude
material in a mixture of acetone (0.9 mL) and water
(0.1 mL), and stirring was continued for 20 h. The mix-
ture was quenched with 10% aq NaHSO3 (2.0 mL) and
washed with brine (5.0 mL). The combined organic
layer was dried (Na2SO4) and evaporated. The residue
was purified by flash chromatography (silica gel, 2:3
EtOAc–hexane) to afford 9 as a white solid (95 mg,
75%).
10. Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521–2522.
11. Marino-Albernas, J.; Verez-Bencomo, V.; Gonzalez-
˜
Rodriguez, L.; Perez-Martinez, C. S.; Gonzalez-Abreu
Castell, E.; Gonzalez-Segredo, A. Carbohydr. Res. 1988,
183, 175.
12. Bhattacharyya, T.; Basu, S. Indian J. Chem. 1991, 30B,
889–890.
13. Hirst, E. L.; Dunstan, S. J. Chem. Soc. 1953, 2332.
14. Rudolf, T.; Stefan, K.; Radoslav, P. Carbohydr. Res. 1977,
53, 276.
15. Vince, P.; Pal, N. Carbohydr. Res. 1980, 81, 184.