Practical synthesis of a tetrasaccharide derivative corresponding to ristomycin A and ristocetin A

Article abstract of DOI:10.1016/S0008-6215(00)00303-7

A practical synthesis of fully benzoylated tetrasaccharide, whose free form is indispensable to the antibiotic ristomycin A for the process of dimerization and binding to the cell wall, was achieved via sequential assembly of the building blocks, allyl 3,4-di-O-benzoyl-α-D-glucopyranoside, 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate, 2-O-acetyl-3,4,6-tri-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate, and 2,3,5-tri-O-benzoyl-α-D-arabinofuranosyl trichloroacetimidate. A one-pot preparation of allyl 3,4-di-O-benzoyl-2-O-tert-butyldimethylsilyl-6-O-triphenylmethyl-α-D- glucopyranoside is described, and regioselective glycosylation is carried out using perbenzoylated sugar trichloroacetimidates as glycosyl donors in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf).

Full text of DOI:10.1016/S0008-6215(00)00303-7

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Carbohydrate Research 330 (2001) 319–324
Practical synthesis of a tetrasaccharide derivative
corresponding to ristomycin A and ristocetin A
Meimei Zhang, Yuguo Du, Fanzuo Kong*
Research Center for Eco-En6ironmental Sciences, Academia Sinica, PO Box 2871,
Beijing 100085, People’s Republic of China
Received 30 August 2000; accepted 16 November 2000
Abstract
A practical synthesis of fully benzoylated tetrasaccharide, whose free form is indispensable to the antibiotic
ristomycin A for the process of dimerization and binding to the cell wall, was achieved via sequential assembly of
the building blocks, allyl 3,4-di-O-benzoyl-a-
trichloroacetimidate, 2-O-acetyl-3,4,6-tri-O-benzoyl-a-
oyl-a- -arabinofuranosyl trichloroacetimidate.
butyldimethylsilyl-6-O-triphenylmethyl-a- -glucopyranoside is described, and regioselective glycosylation is carried
D
-glucopyranoside, 2,3,4-tri-O-benzoyl-a-
-mannopyranosyl trichloroacetimidate, and 2,3,5-tri-O-benz-
one-pot preparation of allyl 3,4-di-O-benzoyl-2-O-tert-
L-rhamnopyranosyl
D
D
A
D
out using perbenzoylated sugar trichloroacetimidates as glycosyl donors in the presence of a catalytic amount of
trimethylsilyl trifluoromethanesulfonate (TMSOTf). © 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Ristomycin; Ristocetin; Regioselective reaction; Oligosaccharide
also slightly adjusted by the formation of ho-
1. Introduction
modimers between two antibiotic monomers.1
Structural elucidation of ristomycin A and
The antibiotic, ristomycin A, which is a
ristocetin A via acetolysis yielded a fully
member of the vancomycin group of antibi-
acetylated tetrasaccharide that was determined
otics, is a glycopeptide containing a complex
to have the following sugar sequence: a- -ara-
D
peptide aglycone moiety and a branched
heterotetrasaccharide side chain. Ristomycin
A, together with its chemical and biological
analogue ristocetin A, have emerged as
promising antibiotics in the treatment of
Gram-positive bacterial infections.1 It has
been well established that the biological action
of vancomycin-type antibiotics involves re-
versible binding to nascent bacterial cell-wall
binopyranosyl-(1“2)-a-
(1“2)-[a- -rhamnopyranosyl-(1“6)]-b-
glucopyranose.3,4 Later, this structure was re-
vised to a- -arabinofuranosyl-(1“2)-a-
mannopyranosyl-(1“2)-[a- -rhamnopyran-
osyl-(1“6)]-b- -glucopyranose by more ex-
tensive spectroscopic studies, i.e., the a-fura-
D
-mannopyranosyl-
L
D
-
D
D-
L
D
nosyl structure for the
D
-arabinosyl unit was
assigned to the oligosaccharide moiety.5–7
The tetrasaccharide residue has proved to
be indispensable to the biological processing
of ristomycin A and ristocetin A, such as in
the process of dimerization and binding to the
cell wall.8 Herein, we report the synthesis of a
ristomycin-related heterotetrasaccharide by a
peptides terminating in
L
-Lys-
D
-Ala- -Ala
D
through hydrogen bonding.1,2 This action is
* Corresponding author. Tel.: +86-10-62936613; fax: +
86-10-62923563.
E-mail address: fzkong@mail.rcees.ac.cn (F. Kong).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00303-7

320
M. Zhang et al. / Carbohydrate Research 330 (2001) 319–324
simple method in which a one-pot synthesis of
Treatment of 2 with 90% trifluoroacetic
acid (TFA) at room temperature gave diol 4
in 91% yield. Attempted detritylation of 2
with \2 equiv of ferric chloride hexahydrate
the 2,6-differentiated a- -glucopyranoside and
D
a regioselective glycosylation were employed.
11
in CH2Cl2 was not satisfactory, and mono-
silylated compounds 3 and diol 4 were ob-
tained in a ratio of 1:1. Elongation of the
reaction time generated 4 as a final product,
while adding 1.5 equiv of FeCl3·6H2O gave 3
and 4 in a 4:1 ratio for 1.5 h at 0 °C.
Regioselective debenzoylation of fully ben-
zoylated
L-rhamnopyranose (5) on C-1 with
NH3 in 3:7 CH3OH–THF (“6), followed by
anomeric activation with CCl3CN and 1,8-di-
azabicyclo[5.4.0]undec-7-ene (DBU) gave the
2. Results and discussion
We have previously shown9 that the use of
benzoylated imidates as glycosyl donors gave
good yields and regioselectivities in glycosyla-
tions. Besides, the common acyl protection
group used in the synthesis greatly simplified
both the preparation of building blocks and
the final deprotection of the product. Accord-
ingly, we designed a practical strategy for the
synthesis of the ristomycin A (or ristocetin A)
related sugar residue using the building blocks
4, 7, 10 and 13.
Synthon 4 was synthesized via a one-pot,
three-step sequential reaction10 as follows. All-
yl a- -glucopyranoside (1) was treated with
D
1.25 equiv of chlorotriphenylmethane (Tr) and
a catalytic amount of 4-dimethylaminopy-
ridine (DMAP) in pyridine at 80 °C. Without
working up, the mixture was regioselectively
silylated with 1.1 equiv of tert-butylchloro-
dimethylsilane (TBDMSCl) and 2 equiv of
imidazole, then benzoylated with benzoyl
chloride to give allyl 3,4-di-O-benzoyl-2-O-
tert-butyldimethylsilyl-6-O-triphenylmethyl-a-
D
-glucopyranoside (2) in a total yield of 79%.
1
The H NMR spectrum of 2 gave H-2 (4.0
ppm) and H-6 (3.21, 3.25 ppm) as upfield
doublets of doublets, while H-3 (5.80 ppm)
and H-4 (5.32 ppm) appeared as downfield
triplets, which clearly indicates the correct
structure of 2 (see Scheme 1).
Scheme 1. (a) TrCl, Py, DMAP; Im, TBDMSCl in DMF;
BzCl, Py; (b) FeCl3·6H2O, DCM; (c) NH3, 3:7 CH3OH–
THF; (d) DBU, CCl3CN; (e) TMSOTf, B −15 °C, CH2Cl2
(anhyd); (f) Ac2O, Py; (g) TMSOTf, 0 °C, CH2Cl2 (anhyd);
(h) 3% CH3COCl, 1:1 CH3OH–CH2Cl2; (i) TMSOTf, 0 °C,
CH2Cl2 (anhyd).

M. Zhang et al. / Carbohydrate Research 330 (2001) 319–324
321
3. Experimental
2,3,4 - tri - O - benzoyl - a - - rhamnopyranosyl-
L
trichloroacetimidate (7) in a total yield of
76%. Regioselective coupling of 7 with diol 4
in anhydrous CH2Cl2 in the presence of TM-
SOTf (0.1 equiv) at −15 °C furnished 1“6
linked disaccharide 8 in 72.5% yield after
column chromatography. To prove the cou-
pling reaction actually occurred at C-6 of
acceptor 4, disaccharide 8 (20 mg) was treated
with Ac2O in pyridine to give the C-2 acety-
lated derivative 9. The 1H NMR spectrum of 9
clearly showed an downfield shift of H-2
(from 3.90 to 5.17 ppm), indicating the pres-
ence of a free C-2 hydroxyl group in 8. The
TMSOTf (0.15 equiv) promoted coupling
reaction of 2-O-acetyl-3,4,6-tri-O-benzoyl-
General methods.—Optical rotations were
determined at 25 °C with a Perkin–Elmer
model 241MC automatic polarimeter. 1H
NMR and 1H–1H COSY spectra were
recorded with a Bruker ARX 400 spectrome-
ter for solutions in CDCl3. Chemical shifts are
given in ppm downfield from internal Me4Si.
Mass spectra were recorded with a VG PlAR-
FOEM mass spectrometer using the FAB
technique to introduce the sample. Thin-layer
chromatography (TLC) was performed on Sil-
ica Gel HF254 (E. Merck) with detection by
charring with 30% (v/v) H2SO4 in MeOH, or
in some cases by a UV detector. Column
chromatography was conducted by elution of
a column of silica gel (100–200 mesh) with
EtOAc–petroleum ether (bp 60–90 °C) or in
some cases with toluene–EtOAc–petroleum
ether as the eluent. Solutions were concen-
trated at B80 °C under diminished pressure.
Allyl 3,4-di-O-benzoyl-2-O-tert-butyldime-
a- -mannopyranosyl trichloroacetimidate (10)
D
with 8 at 0 °C afforded trisacchride 11 in
high yield (83%). The structure of 11 was
1
fully assigned from its H–1H COSY NMR
spectroscopy. The stereochemistry with all
a glycosidic linkages in 11 was established by
1
measuring the JC-1,H-1 heteronuclear coupling
thylsilyl-6-O-triphenylmethyl-h- -glucopyran-
D
constants (1JC-1,H-1 with 173, 172 and 168
Hz at l 98.4, 94.8 and 93.7 ppm, respectively).
No orthoester intermediate was detected in
this case. Compound 11 was selectively
deacetylated12 with acetyl chloride (3% in 1:1
CH3OHꢀCH2Cl2) at room temperature for
20 h to get exclusively the corresponding
trisaccharide acceptor 12. The chemical shift
of H-2 on the mannose residue was moved
upfield from 5.45 (in 11) to 4.41 ppm (in 12),
strongly supporting the fact that no acyl mi-
gration occurred under these reaction condi-
tions. Similarly, the TMSOTf (0.1 equiv)
promoted the coupling reaction of 2,3,5-tri-O-
oside (2).—Compound 115 (5 g, 22.7 mmol)
was dissolved in pyridine (25 mL). A catalytic
amount of DMAP was added into the solu-
tion. Chlorotriphenylmethane (7.6 g, 27.3
mmol) was then added. The mixture was
stirred at 80 °C for 16 h, then cooled down to
0 °C. Imidazole (3.10 g, 45 mmol) was added;
then TBDMSCl (3.75 g, 25 mmol) in DMF (5
mL) was added portionwise over 2 h. The
mixture was stirred at rt for 6 h, at which time
premixed BzCl (7 mL, 55 mmol) and pyridine
(5 mL) was added. The reaction mixture was
stirred at 50 °C for 24 h, then co-evaporated
with toluene to dryness. The residue was dis-
solved in CH2Cl2 (150 mL) and washed with
ice-cold water. The washings were re-extracted
with CH2Cl2. The combined organic phase
was dried, concentrated and subjected to
column chromatography on silica gel with
15:1 petroleum ether–EtOAc as the eluent to
give 2 (14 g, 79%) as a syrup; [h]2D5 +1° (c 4.1,
benzoyl-a- -arabinofuranosyl 2,2,2-trichloro-
D
acetimidate (13)13 with 12 in anhydrous
dichloromethane at 0 °C afforded the target
tetrasaccharide 14 in 80% yield. This tetra-
saccharide could be useful in the total synthe-
sis of ristomycin A or ristocetin A14 after
transformation into a glycosyl donor via
deallylation and activation.9 Furthermore, we
proved here a practical one-pot preparation
1
CHCl3); H NMR (CDCl3): l 0.05, 0.14 (2 s,
2×3 H, Si (CH3)2), 0.77 (s, 9 H, t-Bu), 3.19–
3.27 (m, 2 H, H-6a, H-6b), 4.00 (dd, 1 H, J1,2
3.6, J2,3 9.6 Hz, H-2), 4.14–4.19 (m, 2 H, H-5,
CH2ꢁCHꢀCH2ꢀ), 4.34 (dd, 1 H, J 5.6, 12.8
Hz, CH2ꢁCHꢀCH2ꢀ), 4.97 (d, 1 H, J1,2 4.0 Hz,
of 2,6-differentiated a- -glucopyranoside
D
that may provide an effective strategy for
the synthesis of 2,6-branched oligosacchar-
ides.

322
M. Zhang et al. / Carbohydrate Research 330 (2001) 319–324
J1,2 4.0 Hz, H-1), 5.28 (d, 1 H, J 10.4 Hz,
CH2ꢁCHꢀCH2ꢀ), 5.38 (t, 1 H, J3,4 10 Hz,
H-4), 5.40 (m, 1 H, CH2ꢁCHꢀCH2ꢀ), 5.80 (t, 1
H, J3,4 =J2,3=9.6 Hz, H-3), 5.92–6.02 (m, 1
H, CH2ꢁCHꢀCH2ꢀ), 7.33–7.97 (m, 10 H, 2
Ph). Anal. Calcd for C23H24O8: C, 64.48; H,
5.61. Found: C, 64.21; H, 5.54.
H-1), 5.26 (dd, 1 H, J 10.4, 1.6 Hz,
CH2ꢁCHꢀCH2ꢀ), 5.32 (t, 1 H, J3,4 10 Hz,
H-4), 5.42 (dd, 1 H, J 1.6, 10.4 Hz,
CH2ꢁCHꢀCH2ꢀ), 5.80 (t, 1 H, J3,4 9.6 Hz,
H-3), 6.01–6.03 (m, 1 H, CH2ꢁCHꢀCH2ꢀ),
7.01–7.91 (m, 25 H, 5 Ph). Anal. Calcd for
C48H52O8Si: C, 73.47; H, 6.63. Found: C,
73.69; H, 6.56.
2,3,4-Tri-O-benzoyl-h- -rhamnopyranosyl
L
Allyl 3,4-di-O-benzoyl-2-O-tert-butyldimeth-
trichloroacetimidate (7).—Ammonium was
bubbled into a solution of 516 (6 g, 10.3 mmol)
in 3:7 MeOH–THF (100 mL) for 15 min. The
reaction mixture was stirred at rt for 3 h, then
evaporated to dryness. Purification on a flash
silica gel column using 1:2 EtOAc–petroleum
ether as eluent gave 6, which was dissolved in
anhyd CH2Cl2 (100 mL). To this solution was
added trichloroacetonitrile (10 mL, 100 mmol)
and DBU (1.2 mL). The reaction mixture was
stirred at rt for 6 h, then concentrated. The
residue was purified by silica gel column chro-
matography (3:1 petroleum ether–EtOAc) to
give 7 (4.87 g, 76%) as a syrup; [h]2D5 +110° (c
ylsilyl-h-
D
-glucopyranoside (3) and 3,4-di-O-
benzoyl-h-
D
-glucopyranoside (4).—Method A:
FeCl3·6H2O (2.5 equiv) was added to a mix-
ture of 2 (3 g, 3.8 mmol) in CH2Cl2 (20 mL).
The mixture was stirred for 2 h at rt, then
diluted with more CH2Cl2 (50 mL) and
washed with ice-cold water twice. The wash-
ings were re-extracted with CH2Cl2 (30 mL).
The organic phases were combined, dried and
concentrated, then subjected to column chro-
matography on silica gel with 4:1–1.5:1
petroleum ether–EtOAc as the eluent to give
syrupy 3 (1.06 g, 51%) and syrupy 4 (800 mg,
49%), respectively. Method B: Compound 2
(2.5 g, 3.2 mmol) was dissolved into 90% aq
TFA (15 mL). The mixture was stirred at rt
for 2 h, then toluene (50 mL) was added, and
the solvents were evaporated in vacuo to give
a residue, which was purified by a silica gel
column chromatography (1:1 petroleum
ether–EtOAc) to give 4 (1.26 g, 92%) as a
syrup. Compound 3: [h]2D5 −12° (c 1.3,
1
6.0, CHCl3); H NMR (CDCl3): l 1.43 (d, 3
H, J 6.2 Hz, CH3), 4.40–4.44 (m, 1 H, H-5),
5.78 (t, 1 H, J3,4 10.0 Hz, H-4), 5.90–5.93 (m,
2 H, H-2, H-3), 6.50 (d, 1 H, J1,2 1.6 Hz, H-1),
7.24–8.12 (m, 15 H, 3 Ph), 8.84 (s, 1 H, NH).
Allyl 2,3,4-tri-O-benzoyl-h-
osyl-(1“6)-3,4-di-O-benzoyl-h-
L
-rhamnopyran-
-glucopy-
D
ranoside (8).—To a mixture of 4 (800 mg, 1.87
mmol) and 7 (1.31 g, 2.1 mmol) in anhyd
CH2Cl2 (20 mL) was added Me3SiOTf (10%
equiv) dropwise under a N2 atmosphere at
−15 °C. The mixture was stirred under these
conditions for 1 h, at the end of which time,
TLC (2:1 petroleum ether–EtOAc) indicated
that all the starting material had been con-
sumed. The reaction mixture was neutralized
with Et3N, then concentrated. The product
was purified by column chromatography twice
(3:1 petroleum ether–EtOAc and 0.5:2.5:1 tol-
uene–petroleum ether–EtOAc) to give 8 (1.2
1
CHCl3); H NMR (CDCl3): l 0.04 (2 s, 2×3
H, Si(CH3)2), 0.77 (s, 9 H, t-Bu), 3.66 (dd, 1
H, J5,6a 2.8, J6a,6b 13.2 Hz, H-6a), 3.76 (dd, 1
H, J5,6b 2.0, J6a,6b 12.8 Hz, H-6b), 3.97–3.99
(m, 1 H, H-5), 4.00 (dd, 1 H, J1,2 3.6, J2,3 9.6
Hz, H-2), 4.10 (dd, 1 H, J 5.6, 13.0 Hz,
CH2ꢁCHꢀCH2ꢀ), 4.29 (dd, 1 H, J 5.6, 13.0
Hz, CH2ꢁCHꢀCH2ꢀ), 4.96 (d, J1,2 4.0 Hz,
H-1), 5.25 (d, J 10.4 Hz, CH2ꢁCHꢀCH2ꢀ),
5.34 (t, J3,4 10 Hz, H-4), 5.39 (dd, 1 H, J 1.6,
10.4 Hz, CH2ꢁCHꢀCH2ꢀ), 5.96 (t, J3,4 10 Hz,
H-3), 5.92–6.02 (m, 1 H, CH2ꢁCHꢀCH2ꢀ),
7.26–8.10 (m, 10 H, 2 Ph). Compound 4: [h]D25
1
g, 72.5%); [h]2D5 +84° (c 0.9, CHCl3); H
1
NMR (CDCl3): l 1.26 (d, 3 H, J 6.4 Hz,
CH3IV), 3.77 (dd, 1 H, J5,6a 6.8, J6a,6b 11.6 Hz,
H-6aIII), 3.89–3.92 (m, 2 H, H-2III, H-6bIII),
4.11–4.12 (m, 1 H, H-5IV), 4.25 (q, 1 H, J 6.0,
12.8 Hz, CH2ꢁCHꢀCH2ꢀ), 4.29–4.33 (m, 1 H,
H-5III), 4.45–4.49 (m, 1 H, CH2ꢁCHꢀCH2ꢀ),
5.11–5.13 (m, 2 H, H-1III, H-1IV), 5.33–5.36
+26° (c 2.1, CHCl3); H NMR (CDCl3): l
3.68 (dd, 1 H, J5,6a 3.6, J6a,6b 13 Hz, H-6a),
3.77 (dd, 1 H, J5,6b 2.4, J6a,6b 13 Hz, H-6b),
3,91 (dd, 1 H, J1,2 3.6, J2,3 9.6 Hz, H-2),
3.96–3.98 (m, 1 H, H-5), 4.12 (dd, 1 H, J 5.6,
13.2 Hz, CH2ꢁCHꢀCH2ꢀ), 4.31 (dd, 1 H, J
5.6, 12.8 Hz, CH2ꢁCHꢀCH2ꢀ), 5.10 (d, 1 H,

M. Zhang et al. / Carbohydrate Research 330 (2001) 319–324
323
CH3CO), 3.75 (dd, 1 H, J5,6a 7.2, J6a,6b 12.0
Hz, H-6aIII), 3.91 (dd, 1 H, J5,6b 2.0, J6a,6b 12.0
Hz, H-6bIII), 4.13–4.33 (m, 6 H, H-2III, H-5IV,
H-5II, H-6aII, H-6bII, CH2ꢁCHꢀCH2ꢀ), 4.38–
4.42 (m, 1 H, H-5III), 4.50 (dd, 1 H, J 5.2 Hz,
CH2ꢁCHꢀCH2ꢀ), 5.09 (d, 1 H, J1,2 1.2 Hz,
H-1II), 5.10 (d, 1 H, J1,2 1.2 Hz, H-1IV), 5.25
(d, 1 H, J1,2 3.6 Hz, H-1III), 5.37–5.40 (m, 2
H, H-4, CH2ꢁCHꢀCH2ꢀ), 5.47–5.48 (m, 1 H,
(m, 1 H, CH2ꢁCHꢀCH2ꢀ), 5.42 (t, 1 H, J3,4
10.0 Hz, H-4III), 5.47–5.52 (m,
H,
1
CH2ꢁCHꢀCH2ꢀ), 5.63 (t, 1 H, J3,4 10.0 Hz,
H-3III), 5.71–5.72 (m, 1 H, H-2IV), 5.76–5.79
(m, 2 H, H-3IV, H-4IV), 6.06 (m, 1 H,
CH2ꢁCHꢀCH2ꢀ), 7.25–8.10 (m, 25 H, 5 Ph).
Anal. Calcd for C50H46O15: C, 67.72; H, 5.19.
Found: C, 67.95; H, 5.33.
Allyl 2,3,4-O-tri-benzoyl-h-
osyl-(1“6)-2-O-acetyl-3,4-di-O-benzoyl-h-
-glucopyranoside (9).—Compound 8 (20 mg)
L
-rhamnopyran-
H-2II),
5.56–5.58
(m,
2
H,
H-3II,
D
CH2ꢁCHꢀCH2ꢀ), 5.64 (t, 1 H, J3,4 10 Hz,
H-4II), 5.72–5.73 (dd, 1 H, H-2IV), 5.76–5.78
(m, 2 H, H-3IV, H-4IV), 6.11–6.15 (m, 2 H, J3,4
10 Hz, H-3III, CH2ꢁCHꢀCH2ꢀ), 7.23–8.10 (m,
40 H, 8 Ph). Anal. Calcd for C79H70O24: C,
67.62; H, 4.99. Found: C, 67.47; H, 5.08.
was dissolved in pyridine (1 mL). Then Ac2O
(0.5 mL) was added into the solution. The
mixture was stirred at rt overnight. The sol-
vents were evaporated under reduced pressure
1
to give 9 for NMR testing; H NMR (CDCl3):
l 1.26 (d, 3 H, J 6.2 Hz, CH3IV), 3.79 (dd, 1 H,
J5,6a 7.2, J6a,6b 12 Hz, H-6aIII), 3.89 (dd, 1 H,
J5,6b 2.0, J6a,6b 12 Hz, H-6bIII), 4.11–4.13 (m, 1
H, H-5IV), 4.22 (dd, 1 H, J 6.0, 12.8 Hz,
CH2ꢁCHꢀCH2ꢀ), 4.36–4.45 ( m, 2 H, H-5III,
CH2ꢁCH-CH2ꢀ), 5.11 (d, 1 H, J1%,2% 1.4 Hz,
H-1IV), 5.17 (dd, 1 H, J1,2 3.6, J2,3 10.4 Hz,
H-2III), 5.24-5.25 (d, 1 H, J1,2 3.6 Hz, H-1III),
5.30–5.32 (m, 1 H, CH2ꢁCHꢀCH2ꢀ), 5.39–
5.44 (t, 1 H, J3,4 10.0 Hz, H-4III), 5.46–5.51
(m, 1 H, CH2ꢁCHꢀCH2ꢀ), 5.65 (t, 1 H, J3%,4%
10.0 Hz, H-4IV), 5.69–5.70 (m, 1 H, H-2IV),
5.77 (dd, 1 H, J2%,3% 3.6, J3%,4’% 10.0 Hz, H-3IV),
6.01–6.06 (m, 2 H, H-3, CH2ꢁCHꢀCH2ꢀ),
7.24–8.09 (m, 25 H, 5 Ph). Anal. Calcd for
C52H48O16: C, 67.24; H, 5.17. Found: C, 67.45;
H, 5.30.
Allyl 3,4,6-tri-O-benzoyl-h-
osyl-(1“2)-[2,3,4-tri-O-benzoyl-h-
pyranosyl - (1“6)] - 3,4 - di - O - benzoyl - h -
D
-mannopyran-
L
-rhamno-
D
-
glucopyranoside (12).—Compound 11 (196
mg, 0.14 mmol) was dissolved in 1:1 CH2Cl2-
CH3OH (14 mL), and 3% (volume ratio) of
acetyl chloride was added. The reaction mix-
ture was stirred at rt for 20 h, at the end of
which time, TLC (1:2 EtOAc–petroleum
ether) indicated the reaction was complete.
The solvent was neutralized with Et3N, con-
centrated and subjected to the column chro-
matography (2.5:1 petroleum ether–EtOAc)
to give compound 12 (152 mg, 80%) as a
1
syrup; [h]2D5 +66° (c 0.9, CHCl3); H NMR
(CDCl3): l 1.28 (d, 3 H, J 6.2 Hz, CH3), 3.76
(dd, 1 H, J5,6a 7.2, J6a,6b 12.0 Hz, H-6aIII), 3.92
(dd, J5,6b 4.0, J6a,6b 12.0 Hz, H-6bIII), 4.11–
4.30 (m, 5 H, H-2III, H-5IV, H-5II, H-6aII,
CH2ꢁCHꢀCH2ꢀ), 4.35–4.40 (m, 2 H, H-5III,
H-2II), 4.46–4.51 (m, 2 H, CH2ꢁCHꢀCH2ꢀ,
H-6bII), 5.12 (d, 1 H, J1,2 1.6 Hz, H-1II), 5.14
(d, 1 H, J1,2 1.6 Hz, H-1IV), 5.29 (d, 1 H, J1,2
3.6 Hz, H-1III), 5.34–5.44 (t, 3 H, H-4III, H-3II,
Allyl
mannopyranosyl-(1“2)-[2,3,4-tri-O-benzoyl-
h- -rhamnopyranosyl-(1“6)]-3,4-di-O-benz-
oyl-h- -glucopyranoside (11).—To a mixture
2-O-acetyl-3,4,6-tri-O-benzoyl-h- -
D
L
D
of 8 (920 mg, 1.04 mmol) and 1017 (815 mg,
1.2 mmol) in anhyd CH2Cl2 (10 mL) was
dropped Me3SiOTf (10% equiv) under a N2
atmosphere at 0 °C. The mixture was stirred
under these conditions for 2 h, at the end of
which time, TLC (2:1 petroleum ether–
EtOAc) indicated that all the donor was con-
sumed. The reaction mixture was neutralized
with Et3N, then concentrated. The residue was
purified by column chromatography (0.5:2:1
toluene–petroleum ether–EtOAc) to give
trisaccharide 11 (1.21 g, 83%) as a syrup; [h]D25
CH2ꢁCHꢀCH2ꢀ), 5.52–5.55 (m,
1
H,
CH2ꢁCHꢀCH2ꢀ), 5.66 (t, 1 H, J3,4 10 Hz,
H-4II), 5.72 (dd, 1 H, H-2IV), 5.76–5.79 (m, 2
H, H-3IV, H-4IV), 6.00–6.09 (m, 1 H,
CH2ꢁCHꢀCH2ꢀ), 6.12 (t, 1 H, J3,4 10 Hz,
H-3III), 7.25–8.09 (m, 40 H, 8 Ph). Anal.
Calcd for C77H68O23: C, 67.94; H, 5.00.
Found: C, 67.68; H, 5.16.
Allyl 2,3,5-tri-O-benzoyl-h-
nosyl-(1“2)-3,4,6-tri-O-benzoyl-h-
pyranosyl - (1“2) - [2,3,4 - tri - O - benzoyl - h - -
D
-arabinofura-
1
+90° (c 1.2, CHCl3); H NMR (CDCl3): l
D
-manno-
1.27 (d, 3 H, J 6.4 Hz, CH3), 2.11 (s, 3 H,
L

324
M. Zhang et al. / Carbohydrate Research 330 (2001) 319–324
Acknowledgements
rhamnopyranosyl-(1“6)]-3,4-di-O-benzoyl-h-
-glucopyranoside (14).—To a mixture of
D
compound 12 (100 mg, 0.07 mmol) and 1318
(48 mg, 0.08 mmol) in anhyd CH2Cl2 (5 mL)
was added Me3SiOTf (15% equiv) under a N2
atmosphere at 0 °C. The mixture was stirred
under these conditions for 3 h, then neutral-
ized with Et3N and concentrated. The residue
was purified by column chromatography (2:1
petroleum ether–EtOAc) to give 14 (106 mg,
80%) as a syrup; [h]2D5 +65° (c 0.7, CHCl3);
1H NMR (CDCl3): l 1.28 (d, 3 H, J 6.4 Hz,
CH3), 3.72 (dd, 1 H, J 7.0, 12.0 Hz, H-6aIII),
3.90 (dd, 1 H, J 2.3, 12.0 Hz, H-6bIII), 4.11–
4.26 (m, 6 H, H-2III, H-5IV, H-5II, H-6aII,
H-6bII, CH2ꢁCHꢀCH2ꢀ), 4.35–4.42 (m, 2 H,
This work was supported by CAS KIP-
RCEES9904, KJ952J1561, and NNSF of
China (Projects 29972053 and 39970179).
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