Preparation and diastereomeric separation of an (S)- and (R)-1-(methoxycarbonyl)tridec-10-yl glucoside derivative, a precursor for a monosaccharide constituent of resin glycosides.

Article abstract of DOI:10.1016/S0008-6215(02)00092-7

The 6-O-mesyl derivative of phenyl 1-thio-beta-D-glucopyranoside was prepared from D-glucose as a synthetic equivalent of a 6-deoxy-hexosyl donor. Racemic methyl 11-hydroxytetradecanoate (methyl convolvulinolate) was synthesized by Grignard reaction of propylmagnesium bromide with 10-undecenal followed by hydroboration. Both intermediates were coupled by NIS-TfOH-promoted glycosidation to give a mixture of two diasteromeric glucopyranosides, which were separated on a preparative scale by medium pressure chromatography. One of the products was identified as having the natural (S)-configuration by comparison of its 1H NMR spectrum with an authentic sample prepared from the corresponding chiral hydroxyfatty acid.

Full text of DOI:10.1016/S0008-6215(02)00092-7

Carbohydrate Research 337 (2002) 1047–1053
www.elsevier.com/locate/carres
Note
Preparation and diastereomeric separation of an (S)- and
(R)-1-(methoxycarbonyl)tridec-10-yl glucoside derivative, a
precursor for a monosaccharide constituent of resin glycosides
Shigeru Kobayashi, Jun-ichi Furukawa, Tomoko Sakai, Nobuo Sakairi*
Di6ision of Bioscience, Graduate School of En6ironmental Earth Science, Hokkaido Uni6ersity, Sapporo 060-0810, Japan
Received 18 June 2001; received in revised form 13 March 2002; accepted 25 March 2002
Abstract
The 6-O-mesyl derivative of phenyl 1-thio-b-
D
-glucopyranoside was prepared from D-glucose as a synthetic equivalent of a
6-deoxy-hexosyl donor. Racemic methyl 11-hydroxytetradecanoate (methyl convolvulinolate) was synthesized by Grignard
reaction of propylmagnesium bromide with 10-undecenal followed by hydroboration. Both intermediates were coupled by
NIS–TfOH-promoted glycosidation to give a mixture of two diasteromeric glucopyranosides, which were separated on a
preparative scale by medium pressure chromatography. One of the products was identified as having the natural (S)-configuration
by comparison of its 1H NMR spectrum with an authentic sample prepared from the corresponding chiral hydroxyfatty acid.
© 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Resin glycosides; Convolvulinolic acid; 6-Deoxyhexose; Diastereomeric separation
1. Introduction
These features of bioactivity and structure have stim-
ulated work on total synthesis of resin glycosides.7,8
Our previous work on the total synthesis of calonyctin
A28 (1) showed that a suitably protected (S)-1-
Resin glycosides are plant glycolipids, isolated mainly
from such Convolvulaceae plants as morning glory.
Numerous resin glycosides have been isolated and their
structures determined spectroscopically.1 Some of them
have bioactivities such as cytotoxic activity against
human breast cancer cell lines,2 antimicrobial activity,3
and controlling effects on plant growth.4,5
(methoxycarbonyl)tridec-10-yl
b-D-glucopyranoside
(2S) was one of the key intermediates. Although the
aglycon moiety of 2S has been prepared stereoselectivly
from
L
-glutamic acid, the process requires 16 steps.8
Schmidt and his co-workers used racemic jalapinonic
acid in their total synthesis of a tetasaccharidic resin
glycoside and they separated diasteromers at the final
Resin glycosides frequently contain such deoxy-
genated hexopyranoses as
D-quinovose, D-fucose, and
L
-rhamnose, and have optically active fatty acids such
stage of the synthesis.7a Since a 2-O-glycosylated b-
D-
as jalapinolic acid [(S)-11-hydroxyhexadecanoic acid]
and convolvulinolic acid6 [(S)-11-hydroxytetradecanoic
acid] as the aglycon. The most notable structural fea-
ture of resin glycosides is that one of the sugar hydroxyl
groups is intramolecularly acylated with the carboxyl
group in the aglycon moiety to form a macrolide
structure.
quinovose component appears at the reducing end of
most resin glycosides, a concise preparation of 2S
would be useful for synthesizing various resin gly-
cosides. We describe here the preparation of racemic
methyl convolvulinolate and the separation of the de-
sired (S)-isomer after coupling with a monosaccharide.
2. Results and discussion
Synthesis of two glycosyl donors 6 and 7 as precur-
sors of a 6-deoxyhexoside unit is summarized in Scheme
* Corresponding author. Tel./fax: +81-11-706-2257.
E-mail address: nsaka@ees.hokudai.ac.jp (N. Sakairi).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00092-7

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S. Kobayashi et al. / Carbohydrate Research 337 (2002) 1047–1053
1. The known phenyl 3-O-benzyl-4,6-O-benzylidene-1-
thio-b-
-glucopyranoside9 (3) was benzoylated to give
used for the next reaction. The mesyloxy group in 6 was
reduced with sodium borohydride in DMF at 70 °C to
give the stable deoxy derivative 7 in 62% yield. Both the
mesylate 6 and the 6-deoxy derivative 7 were used as
glycosyl donors for the next glycosidation.
Synthesis of the racemic aglycon moiety, methyl 11-
hydroxydecanoate (12), was initiated by a Grignard
reaction of propylmagnesium bromide 8 with 10-unde-
cenal 9. In order to introduce a primary hydroxyl
group, the resulting tetradecen-4-ol 10 was subjected to
hydroboration with borane·tetrahydrofuran complex
with a subsequent oxidative workup (Scheme 2). Selec-
tive oxidation of the primary hydroxyl group of the
resulting tetradecan-1,11-diol 11 was next achieved by a
two-phase reaction in the presence of 2,2,6,6-tetra-
methylpiperidine 1-oxyl, free radical (TEMPO) as the
D
the 2-benzoate 4, from which the benzylidene acetal
was removed by reductive cleavage. After considering
many reagent systems for the reduction,10 we succeeded
in preparing the desired 6-hydroxyl derivative 5 by
using borane·dimethylamine complex–boron trifluoride
etherate as reported by Kusumoto.11 This reagent sys-
tem in dichloromethane at −20 °C allowed regioselec-
tive reduction of the O-benzylidene group without
affecting other protecting groups. The yield of the
4-O-benzyl derivative 5 was 77%, and the free hydroxyl
group was mesylated in pyridine to give the glycosyl
donor 6 in 89% yield. Because the mesylate 6 was
unstable, freshly prepared material whose purity was
1
confirmed by both H and 13C NMR spectroscopy was
Scheme 1.
Scheme 2.

S. Kobayashi et al. / Carbohydrate Research 337 (2002) 1047–1053
1049
Scheme 3.
1
Fig. 1. H NMR spectra of compounds 2R, 2S, and 2RS.
catalyst.12 Thus, 11 was treated with TEMPO and
N-chlorosuccinimide (NCS) in CH2Cl2–phosphate
buffer containing tetrabutylammonium chloride as the
phase-transfer catalyst to give an aldehyde intermedi-
ate, which was further oxidized by sodium chlorite to
the carboxylic acid. After treatment with diazomethane
in diethyl ether, the racemic methyl ester 12 was iso-
lated in 76% overall yield.
14RS (Scheme 3). Unexpectedly, neither spectroscopic
nor chromatographic differences were observed be-
tween both pairs of diastereomers, 13RS and 14RS.
Next, we examined the glycosidation using the more
labile 6-O-mesyl thioglycoside 6. On treatment of 12
and freshly prepared 6 in CH2Cl2 with N-iodosuccin-
imide (NIS)–TfOH,13 the reaction proceeded smoothly
to give the b-glycoside 2RS as
a mixture of
Having prepared both glycosyl donors 6 and 7, the
racemic acceptor 12, glycosidation and subsequent sep-
aration of the resulting diastereomers were examined
next. At first, the deoxy donor 7 and methyl tetra-
decanoate 12 were reacted in the presence of methyl
trifluoromethanesulfonate (4.5 equiv) as a promoter,
giving the 6-deoxygenated O-glycoside 13RS in 89%
yield as a mixture of diastereomers. Zemple´n deac-
ylation of 13RS gave the 2-unprotected derivatives
diastereomers in 83% yield. The stable O-glycosides
thus obtained were found to be separable by medium
pressure chromatography on a column of silica gel,
using hexane–acetone as the eluant. The isolated yields
of the faster- and slower-moving products were 29 and
32%, respectively, together with 20% of the recovered
mixture. In order to determine their absolute configura-
tion, we also synthesized the corresponding enantiomer-
ically pure S-isomer 2S by similar glycosylation of

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S. Kobayashi et al. / Carbohydrate Research 337 (2002) 1047–1053
methyl (S)-11-hydroxytetradecanoate.8 As shown in the
1H NMR spectrum of the products 2R and 2S (Fig. 1),
all peaks due to protons of the glucose residue and
H-11, the chiral center, are found to be superposable.
However, protons of the terminal C-methyl groups of
the aglycon moieties of the faster- and slower-moving
products were observed at l 0.551 and 0.860 as triplets,
respectively. Comparing the spectra to that of an au-
thentic sample, we concluded that the latter, namely,
the slower-moving product, was the natural 2S type.
This upfield shift of the methyl group of the faster-mov-
ing product 2R is probably due to the shielding effect of
the benzene ring of the 2-O-benzoyl group.
(CHCl3–hexane); [h]D +37.5° (c 1.16, CHCl3); 1H
NMR (CDCl3) l 8.03–7.08 (m, 20 H, 4 C6H5), 5.60 (s,
1 H, PhCH), 5.29 (dd, 1 H, J1,2 10.05, J2,3 8.31 Hz,
H-2), 4.85 (d, 1 H, H-1), 4.81 (d, 1 H, J 11.9 Hz, 1/2
PhCH2), 4.66 (d, 1 H, 1/2 PhCH2), 4.42 (dd, 1 H, J 5.10
Hz, H-6), 3.89 (t, 1 H, J2,3 8.31 Hz, H-3), 3.88–3.77 (m,
2 H, H-4,6), 3.61–3.53 (m, 1 H, H-5); 13C NMR
(CDCl3) l 165.60 [C(O)Ph], 101.85 (PhCHO2), 87.56
(C-1), 81.99 (C-2), 74.82 (PhCH2), 71.16 (C-5), 69.16
(C-6); Anal. Calcd for C33H30O6S: C, 71.46; H, 5.45; S,
5.78. Found: C, 71.46; H, 5.53; S, 5.71.
Phenyl 2-O-benzoyl-3,4-di-O-benzyl-1-thio-i-D-glu-
copyranoside (5).—To a solution of 4 (3.013 g, 5.43
mmol) and borane·dimethylamine complex (2.9 g, 27
mmol) in dry CH2Cl2 (200 mL) was added dropwise
boron trifluoride etherate (3.4 mL, 27.1 mmol) with
stirring at 0 °C under nitrogen. The mixture was stirred
at the same temperature for 30 min, poured slowly into
ice-cold aq NaHCO3 with vigorous stirring, and ex-
tracted with CHCl3. The extract was successively
washed with 2 M HCl, aq satd NaHCO3, and brine,
dried (Na2SO4), and evaporated. The residue was chro-
matographed on a column of silica gel using 5:1 hex-
ane–EtOAc to give the 3,4-di-O-benzyl derivative 5
(2.324 g, 76.9%) as a white solid; mp 108.6–110.2 °C
(EtOH); [h]D +43.1° (c 0.64, CHCl3); 1H NMR
(CDCl3) l 8.05–7.09 (m, 20 H, 4 C6H5), 5.27 (dd, 1 H,
J1,2 9.72, J2,3 9.36 Hz, H-2), 4.85 (d, 1 H, J 10.98 Hz,
1/2 PhCH2), 4.83 (d, 1 H, H-1), 4.74 (d, 1 H, 1/2
PhCH2), 4.65 (d, 2 H, 1/2 PhCH2), 3.95–3.89 (m, 1 H,
H-6), 3.86 (t, 1 H, J 9.00 Hz, H-3), 3.77–3.70 (m, 1 H,
H-6), 3.69 (t, 1 H, J 9.00 Hz, H-4), 3.53–3.48 (m, 1 H,
H-5), 1.97 (t, 1 H, J 6.90 Hz, 6-OH); 13C NMR
In summary, we have developed a synthesis of the
b- -glycoside 2S with the S configuration by prepara-
D
tion of racemic methyl convolvulinolate, glycosidation
of the 6-O-mesyl donor, and separation of the
diastereomers. Compound 2S may be regarded as a key
and common intermediate for synthesis of various resin
glycosides.
3. Experimental
General procedures.—Melting points were deter-
mined in a capillary with a Yamato melting-point ap-
paratus (model MP-21) and are uncorrected. Optical
rotations were determined with a Horiba Sepa-300 po-
1
larimeter. H NMR (300.13 MHz) and 13C NMR (75.5
MHz) spectra were recorded with a Bruker ASX-300
spectrometer for solutions in CDCl3. Chemical shifts
(l) are given in ppm relative to internal Me4Si. TLC
and HPTLC were performed using precoated glass
plates of Silica Gel 60 F254 (E. Merck, Darmstadt,
Germany) with layer thicknesses of 0.25 and 0.2 mm,
respectively. The spots were visualized under a UV
lamp at 254 nm and by spraying 5% aq H2SO4 followed
by heating on a hot plate for a few minutes. Column
chromatography and medium-pressure column chro-
matography were performed on Silica Gel 60 (230–400
mesh) and on LiChroprep Si-60 (E. Merck, Darmstadt,
(CDCl3)
l 165.17 [C(O)Ph], 83.99 (C-2), 75.31
(PhCH2), 75.15(PhCH2), 72.46 (C-5), 62.01 (C-6); Anal.
Calcd for C33H32O6S: C, 71.20; H, 5.79; S, 5.76. Found:
C, 71.23; H, 5.87; S, 5.71.
Phenyl
2-O-benzoyl-3,4-di-O-benzyl-6-O-mesyl-1-
thio-i- -glucopyranoside (6).—To a solution of 5 (2.07
D
g, 3.72 mmol) in pyridine (30 mL) mesyl chloride (0.87
mL, 11 mmol) was added dropwise with stirring at
0 °C. The mixture was stirred at 0 °C for 2 h, quenched
with crushed ice, and extracted with CHCl3. The extract
was successively washed with 2 M HCl, aq satd
NaHCO3, and brine, dried (Na2SO4), and evaporated.
The residue was chromatographed on a column of silica
gel using 15:1 toluene–EtOAc to give the unstable
6-mesylate 6 (2.10 g, 88.9%); 1H NMR (CDCl3) l
8.05–7.12 (m, 20 H, 4 C6H5), 5.27 (t, 1 H, J1,2=J2,3
9.56 Hz, H-2), 4.87 (d, 1 H, J 10.89 Hz, 1/2 PhCH2),
4.83 (d, 1 H, H-1), 4.74 (d, 1 H, 1/2 PhCH2), 4.66 (d, 1
H, 1/2 PhCH2), 4.64 (d, 1 H, 1/2 PhCH2), 4.50 (dd, 1
H, J5,6 1.46, J6,6 11.44 Hz, H-6), 4.32 (dd, 1 H, H-6),
3.88 (t, 1 H, J2,3=J3,4 8.71 Hz, H-3), 3.70–3.63 (m, 1
H, H-5), 3.63 (t, 1 H, J4,5 8.69 Hz, H-4), 3.00 (s, 3 H,
OSO2CH3); 13C NMR (CDCl3) l 165.12 [C(O)Ph],
,
Germany), respectively. Molecular sieves 4 A were acti-
vated at 160–180 °C under diminished pressure prior to
use.
Phenyl 2-O-benzoyl-3-O-benzyl-4,6-O-benzylidene-1-
thio-i-
D
-glucopyranoside (4).—To a solution of phenyl
- glucopyrano-
3-O-benzyl-4,6-O-benzylidene-1-thio-b-
D
side9 (3, 9.20 g, 20.43 mmol) in pyridine (100 mL),
benzoyl chloride (7.1 mL, 61.0 mmol) was added drop-
wise. The mixture was stirred at rt for 12 h, quenched
with ice–water, and extracted with CHCl3. The extract
was successively washed with 2 M HCl, aq satd
NaHCO3, and brine, dried (Na2SO4), and evaporated.
The residue was chromatographed on a column of silica
gel using 30:1 toluene–EtOAc to give the 2-benzoate 4
(10.84 g, 94%) as a white solid; mp 178.0–179.6 °C

S. Kobayashi et al. / Carbohydrate Research 337 (2002) 1047–1053
1051
86.29 (C-1), 84.01 (C-2), 75.45 (PhCH2), 75.24
(PhCH2), 72.21 (C-5), 68.29 (C-6), 37.84 (OSO2CH3).
Because this compound was unstable, satisfactory ele-
mental analysis data were not obtained, and freshly
prepared material was used for the next step.
the residue on silica gel using (5:1“3:1) toluene–
EtOAc gave 1,11-tetradecanediol 11 (8.7 g, 78%); H
1
NMR (CDCl3) l 3.64 (t, 2 H, J3,4 6.60 Hz, CH2-1), 3.61
(m, 1 H, CH-11), 1.64–1.28 (m, 22 H), 0.929 (t, 3 H, J
6.75 Hz, CH3-14); 13C NMR (CDCl3) l 72.34 (C-11),
63.69 (C-1), 14.72 (C-14). MS (FD): C14H30O2 (M) for
230.22; Found: m/e 229 [M−H]+, 213 [M−OH]+,
194 [M−H2O]+; HRMS (FAB) m/z for C14H29O
[M−OH]+, Calcd: 213.2218; Found: 213.2206.
Phenyl 2-O-benzoyl-3,4-di-O-benzyl-6-deoxy-1-thio-
i- -glucopyranoside (7).—To a solution of 6 (408 mg,
D
0.64 mmol) in DMF (20 mL) was added NaBH4 (242
mg, 6.4 mmol). The mixture was heated at 70 °C and
stirred at for 6 h, quenched with crushed ice, and
extracted with CHCl3. The extract was successively
washed with aq 10% NH4Cl, aq satd NaHCO3, and
brine, dried (MgSO4), and evaporated. The residue was
chromatographed on a column of silica gel using 15:1
toluene–EtOAc to give the 6-deoxy derivative 7 (216
mg, 62.1%) as an amorphous solid; [h]D +53.1° (c
Methyl 11-hydroxytetradecanoate (12).—A solution
of the diol 11 (4.34 g, 18.8 mmol) in CH2Cl2 (40 mL)
and 0.5 M carbonate buffer (pH 8.6, 40 mL) was
vigorously stirred at rt. To the mixture was added
tetra-n-butylammonium chloride (522 mg, 18.8 mmol),
2,2,6,6,-tetramethylpiperidin-1-yloxy radical (TEMPO,
294 mg, 18.8 mmol), and N-chlorosuccinimide (3.77 g,
28.2 mmol). The mixture was stirred for 1.5 h, and
partitioned between CH2Cl2 and water. The organic
layer was washed with brine twice, and evaporated
below 30 °C under diminished pressure. To a solution
of the residue in t-butyl alcohol (80 mL) was added
2-methyl-2-butene (30 mL), water (80 mL), and
Na2HPO4·12 H2O (3.5 g, 9.8 mmol). To the resulting
mixture, stirred vigorously at rt, was added NaClO2
(80%, 3.5 g, 31 mmol), and the mixture was stirred for
1 h, extracted with CHCl3. The extract was washed
with 1 M HCl three times and with water twice, and
evaporated. The residue was dissolved in Et2O (50 mL),
and an ethered solution of CH2N2, generated from
methyl nitrosomethylguanidine, was added to the solu-
tion. The solution was allowed to stand for 2 h,
quenched with AcOH, washed successively with aq
NaHCO3 and brine, dried (MgSO4), and evaporated.
The residue was chromatographed on a column of silica
gel with 20:1 toluene–EtOAc to give methyl 11-
hydroxytetradecanoate (12, 3.7 g, 76%) as a white solid;
1
1.00, CHCl3); H NMR (CDCl3) l 8.05–7.11 (m, 20 H,
4 C6H5), 5.26 (t, 1 H, J1,2=J2,3 9.5 Hz, H-2), 4.86, 4.66
(d, 1 H, J 11.2 Hz, PhCH2), 4.76 (d, 1 H, H-1), 4.72,
4.61 (d, 1 H, PhCH2), 3.80 (t, 1 H, J3,4 9.1 Hz, H-3),
3.56–3.50 (m, 1 H, H-5), 3.34 (t, 1 H, J4,5 9.3 Hz, H-4),
1.39 (d, J5,6 6.0 Hz, 3 H, H-6); 13C NMR (CDCl3) l
165.7 [C(O)Ph], 86.6 (C-1), 84.6 (C-2), 76.4 (PhCH2),
75.9 (PhCH2), 73.2 (C-5), 18.6 (C-6); HRMS (FAB)
m/z for C33H33O5S [M+H]+, Calcd: 541.2049; Found:
541.2026.
1-Tetradecen-11-ol (10).—A solution of 1-brompro-
pane (22.9 g, 0.186 mol) in dry Et2O (50 mL) was added
dropwise to a stirred mixture of dry Et2O (50 mL) and
magnesium ribbon (4.14 g, 0.169 mol) under nitrogen.
After cooling at −20 °C, a solution of 10-undecenal 9
(20.3 g, 0.124 mol) in Et2O was added dropwise to the
resulting mixture and stirred for 1 h. The mixture was
quenched with 2 M HCl and extracted with Et2O. The
extract was successively washed with satd NaHCO3 and
brine, dried (Na2SO4), and evaporated. Column chro-
matography of the residue on silica gel using 15:1
1
mp 41.4–42.0 °C (EtOAc–hexane); H NMR (CDCl3),
1
toluene–EtOAc gave the alcohol 10 (17.0 g, 64.6%); H
l 3.67 (s, 3 H, CO2CH3), 3.60 (m, 1 H, CH-11), 2.30 (t,
2 H, J 7.54 Hz, CH2-2), 1.28–1.64 (m, 20 H), 0.93 (t, 3
H, J 6.84 Hz, CH3-14); 13C NMR (CDCl3) l 174.25
[C(O)OCH3], 71.52 (C-11), 17.42 [C(O)OCH3], 14.02
(C-14); Anal. Calcd for C15H30O3: C, 69.72; H, 11.70.
Found: C, 69.60; H, 11.61.
NMR (CDCl3) l 5.81 (m, 1 H, ꢀCH), 4.95 (m, 2 H,
ꢀCH2), 3.61 (m, 1 H, CH-11), 2.04 (q, 2 H, J 7.00 Hz,
CH2-3), 1.68–1.20 (m, 18 H,), 0.929 (t, 3 H, J 6.90 Hz,
CH3-14); 13C NMR (CDCl3) l 139.82 (CHꢀCH2),
114.69 (CH2ꢀCH), 72.31 (C-11), 14.71 (C-14); MS
(FD): C14H28O (M) for 212.21; Found: m/z 211 [M−
H]+.
1-(Methoxycarbonyl)tridec-10-yl 2-O-benzoyl-3,4-di-
O-benzyl-6-deoxy-i-
D
-glucopyranoside
(13RS).—A
1,11-Tetradecanediol (11).—To a solution of alcohol
10 (10.2 g, 0.0480 mol) in dry tetrahydrofuran (150 mL)
was added a 1 M solution of borane in tetrahydrofuran
(44 mL, 0.044 mol) at 0 °C under nitrogen. The solu-
tion was stirred at 0 °C for 2 h, and quenched by
careful addition of aq tetrahydrofuran. Aqueous NaOH
(2 M, 16 mL) and 30% aq H2O2 (10.5 mL) was succes-
sively added to the mixture. The mixture was stirred at
45 °C for 30 min and, extracted twice with Et2O. The
combined extracts were washed with brine, dried
(Na2SO4), and evaporated. Column chromatography of
suspension of methyl 11-hydroxytetradecanoate 12 (126
mg, 0.49 mmol), phenyl 2-O-benzoyl-3,4-di-O-benzyl-6-
deoxy-1-thio-b- -glucopyranoside (7, 222 mg, 0.41
D
,
mmol), and molecular sieves 4 A (100 mg) in CH2Cl2
(5.2 mL) was stirred under nitrogen for 30 min at rt.
Methyl triflate (207 mL, 1.8 mmol) was added to the
mixture. After 24 h, the suspension was neutralized
with pyridine and filtered through a Celite pad. The
filtrate was diluted with CHCl3, washed successively
with aq Na2S2O3, aq NaHCO3, and brine, dried
(Na2SO4), and evaporated. The residue was subjected

1052
S. Kobayashi et al. / Carbohydrate Research 337 (2002) 1047–1053
to chromatography on a column of silica gel with 5:1
hexane–EtOAc, giving the b-glycoside 13RS (251 mg,
89%) as an amorphous solid; 1H NMR (CDCl3), l
8.02–7.12 (m, 15 H, 3 C6H5), 5.23 (dd, 1 H J1,2 8.02,
J2,3 8.69 Hz, H-2), 4.87 (d, 1 H, J 10.88 Hz, 1/2
PhCH2), 4.73 (d, 1 H, 1/2 PhCH2), 4.64 (d, 1 H, 1/2
PhCH2), 4.61 (d, 1 H, 1/2 PhCH2), 4.49 (d, 1 H, H-1),
3.76 (t, 1 H, J2,3=J3,4 8.73 Hz, H-3), 3.67, 3.66 (s×2,
3 H, COOCH3), 3.47 (m, 1 H, H-5), 3.34 (t, 1 H,
raphy using (10:1“6:1) hexane–acetone to give the
syrupy (R)-isomer 2R (73 mg, 29%) as the first fraction;
[h]D +17.4° (c 0.34, CHCl3); 1H NMR (CDCl3) l
8.02–7.14 (m, 15 H, 3 C6H5), 5.23 (t, 1 H, J 8.10, J 9.24
Hz, H-2), 4.90 (d, 1 H, J 10.86 Hz, 1/2 PhCH2), 4.75 (d,
1 H, 1/2 PhCH2), 4.68 (d, 1 H, 1/2 PhCH2), 4.67 (d, 1
H, 1/2 PhCH2), 4.57 (d, 1 H, J1,2 8.04 Hz, H-1), 4.51
(dd, 1 H, J5,6a 1.52, J6a,6b 11.33 Hz, H-6a), 4.33 (dd, 1
H, J5,6b 4.32 Hz, H-6b), 3.85 (t, 1 H, J2,3=J3,4 8.99 Hz,
H-3), 3.71–3.56 (m, 1 H, H-5), 3.67 (t, 1 H, J3,4=J4,5
9.75 Hz, H-4), 3.65 (s, 3 H, COOCH3), 3.52 (m, 1 H,
OCH), 3.05 (s, 3 H, OSO2CH3), 2.29 (t, 2 H, J 7.52 Hz,
OCOCH2), 1.63–0.85 (m, 20 H, 10×CH2), 0.551 (t, 3
H, J 7.12 Hz, CH3); 13C NMR (CDCl3) l 174.83
[C(O)OCH3], 165.56 [C(O)Ph], 101.38 (C-1), 83.13 (C-
2), 75.69 (CH2Ph), 75.64 (CH2Ph), 73.52 (C-5), 69.01
(C-6), 18.36 [C(O)OCH3], 14.41 (C-14); Anal. Calcd for
C43H58O11S: C, 65.96; H, 7.47; S, 4.10. Found: C, 65.83;
H, 7.40; S, 4.18.
J3,4=J4,5 9.27 Hz, H-4), 2.29 (t, 2 H, J 7.52 Hz,
OCOCH2), 1.63–0.85 (m, 23 H, 10 CH2, H-6), 0.88,
0.57 (t×2, 3 H, J 7.12 Hz, CH3); 13C NMR (CDCl3) l
174.83 [C(O)OCH3], 165.56 [C(O)Ph], 101.14 (C-1),
75.71 (CH2Ph), 75.36 (CH2Ph); HRMS (FAB) m/z for
C42H56O8Na [M+Na]+, Calcd: 711.3872; Found:
711.3881.
(S)-1-(Methoxycarbonyl)tridec-10-yl 3,4-di-O-benzyl-
6-deoxy-i- -glucopyranoside (14).—To a solution of
D
monosaccharide derivative 13 (786 mg, 1.1 mmol) in
MeOH (20 mL) was added 3 M NaOMe (0.5 mL). The
solution was heated at 40 °C, stirred for 2 days, and
neutralized by Amberlite IR-120B (H+ form). The resin
was filtered and washed with MeOH and the filtrate
and the washings were combined and concentrated.
Column chromatography of the residual syrup with
25:1 toluene–EtOAc as eluant gave the 2-OH derivative
Further elution of the column with 6:1 hexane–ace-
tone gave a mixture of 2R and 2S (53 mg, 20%) and the
pure (S)-isomer 2S (78 mg, 32%) as a syrup; [h]D
1
+26.6° (c 0.344 CHCl3); H NMR (CDCl3) l 8.02–
7.14 (m, 15 H, 3 C6H5), 5.22 (t, J1,2 8.15, J2,3 9.44 Hz,
1 H, H-2), 4.89 (d, 1 H, J 10.86 Hz, 1/2 PhCH2), 4.74
(d, 1 H, 1/2 PhCH2), 4.67 (d, 1 H, 1/2 PhCH2), 4.66 (d,
1 H, 1/2 PhCH2), 4.56 (d, 1 H, H-1), 4.51 (dd, 1 H, J5,6a
1.79, J6a,6b 11.36 Hz, H-6), 4.31 (dd, 1 H, J5,6b 4.40 Hz,
H-6), 3.85 (t, 1 H, J2,3=J3,4 9.45 Hz, H-3), 3.67 (s, 3 H,
COOCH3), 3.69–3.56 (m, 2 H, H-4, H-5), 3.52 (m, 1 H,
OCH), 3.05 (s, 3 H, OSO2CH3), 2.29 (t, 2 H, J 7.53 Hz,
OCOCH2), 1.61–0.84 (m, 20 H, 10×CH2), 0.860 (t, 3
H, J 7.10 Hz, CH3); 13C NMR (CDCl3) l 174.81
[C(O)OCH3], 165.49 [C(O)Ph], 101.43 (C-1), 83.15 (C-
2), 75.67 (CH2Ph), 73.48 (C-5), 69.04 (C-6), 18.99
[C(O)OCH3], 14.63 (C-14); Anal. Calcd for
C43H58O11S: C, 65.96; H, 7.47; S, 4.10. Found: C, 65.83;
H, 7.40; S, 4.18.
1
14RS (516 mg, 77%) as an amorphous solid; H NMR
(CDCl3) l 7.40–7.16 (m, 10 H, 2 C6H5), 4.95 (d, 1 H,
J 11.3 Hz, 1/2CH2Ph), 4.88 (d, 1 H, 1/2CH2Ph), 4.82
(d, 1 H, 1/2 CH2Ph), 4.63 (d, 1 H, 1/2 CH2Ph), 4.25 (d,
1 H, J 7.2 Hz, H-1), 3.66 (s, 3 H, CO2Me), 3.63–3.47
(m, 3 H, CHO, H-2, H-3), 3.43–3.39 (m, 1 H, H-5),
3.20 (t, 1 H, J 8.8 Hz, H-4), 2.30 (t, 2 H, J 7.3 Hz,
CH2CO2), 1.63–1.27 (m, 23 H, 10 CH2, H-6), 0.90 (t, 3
H, J 7.1 Hz, CH3); Anal. Calcd for C35H52O7: C, 71.89;
H, 8.96. Found: C, 71.67; H, 8.79.
(S)-1-(Methoxycarbonyl)tridec-10-yl (2S) and (R)-1-
(methoxycarbonyl)tridec-10-yl
2-O-benzoyl-3,4-di-O-
benzyl-6-O-mesyl-i- -glucopyranoside (2R).—A sus-
pension of methyl 11-hydroxytetradecanoate (12, 70
mg, 0.27 mmol), phenyl 2-O-benzoyl-3,4-di-O-benzyl-6-
D
The (S)-isomer 2S was also synthesized by coupling
optically active methyl (S)-11-hydroxytetradecanoate8
(11 mg, 0.042 mmol) with thioglycoside 6 (43 mg, 0.067
mmol) using NIS (18 mg, 0.081 mmol) and TfOH (3
O-mesyl-1-thio-b-
D
-glucopyranoside (6, 201 mg, 0.317
1
mmol), N-iodosuccinimide (106 mg, 0.471 mmol), and
mL) under the same conditions, in 46% yield, and its H
molecular sieves 4 A (100 mg) in CH2Cl2 (3 mL) was
and 13C NMR spectra were identical with those already
described.
,
stirred under nitrogen for 30 min and cooled to
−20 °C. Trifluoromethanesulfonic acid (3 mL) was
added to the mixture. After 20 min, the wine-red col-
ored suspension was made neutral with pyridine and
filtered through a Celite pad. The filtrate was diluted
with CHCl3, washed successively with aq Na2S2O3, aq
NaHCO3, and brine, dried (Na2SO4), and evaporated.
The residue was subjected to chromatography on a
column of silica gel with 5:1 hexane–EtOAc, giving a
1:1 diastereomeric mixture of the b-glycoside 2RS (204
Acknowledgements
This work was supported by Grant-in-Aid for Scien-
tific Research on Priority Areas from the Ministry of
Education, Science, Sports, and Culture of Japan (No.
0924010) and by Research Fellowship to J.F. of the
Japan Society for the Promotion of Science (JSPS). We
would like to thank Ms A. Maeda and Ms S. Oka
(Center for Instrumental Analysis, Hokkaido Univer-
1
mg, 83%), estimated by H NMR analysis. The mixture
was subjected to medium-pressure column chromatog-

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