Synthesis of a thio-linked Lewis A (Lea) epitope

Article abstract of DOI:10.1016/S0008-6215(97)10044-1

The synthesis of heptyl (α-L-fucopyranosyl)-(1 → 4)-S-[(β-D- galactopyranosyl)-(1 → 3)]-1,4-dithio-β-D-glucopyranoside (2), as thio- linked Lewis A analogue was based on thexyldimethylsilyl 3-O-allyl-2-O- benzoyl-6-O-(4-methoxybenzyl)-4-thio-β-D-glucopyranoside (15) which was readily obtained from D-galactose. Reaction of 15 with O-3,4-di-O-acetyl-2- O-(4-methoxybenzyl)-α-L-fucopyranosyl trichloroacetimidate (8) as fucosyl donor afforded the α-(1 → 4)-thio-linked disaccharide. Replacement of the 4-methoxybenzyl groups by acetyl groups and removal of the 3a-O-allyl group afforded as 3a-O-unprotected acceptor thexyldimethylsilyl (2,3,4-tri-O- acetyl-α-L-fucopyranosyl)-(1 → 4)-S-6-O-acetyl-2-O-benzoyl-4-thio-β-D- glucopyranoside (19), which gave with 2,3,4,6-tetra-O-acetyl-α-D- galactopyranosyl trichloroacetimidate as galactosyl donor (20) the trisaccharide. Transformation into a trichloroacetimidate as glycosyl donor, glycosylation of heptylmercaptan, and then removal of the O-acyl protective groups afforded target molecule 2.

Full text of DOI:10.1016/S0008-6215(97)10044-1

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Carbohydrate Research 306 1998 81–91
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1
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Synthesis of a thio-linked Lewis A Le epitope
)
Thomas Eisele, Rainer Windmuller, Richard R. Schmidt
¨
Fakultat Chemie, UniÕersitat Konstanz, Postfach 5560 M 725, D-78457 Konstanz, Germany
¨
¨
Received 26 May 1997; revised 8 August 1997
Abstract
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. Ž
.
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The synthesis of heptyl a-L-fucopyranosyl - 1™4 -S- b-D-galactopyranosyl - 1™3 -
Ž .
1,4-dithio-b-D-glucopyranoside 2 , as thio-linked Lewis A analogue was based on
Ž
.
thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-6-O- 4-methoxybenzyl -4-thio-b-D-glucopyrano-
side 15 which was readily obtained from D-galactose. Reaction of 15 with O-3,4-di-O-
acetyl-2-O- 4-methoxybenzyl -a-L-fucopyranosyl trichloroacetimidate 8 as fucosyl donor
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.
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.
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.
afforded the a- 1™4 -thio-linked disaccharide. Replacement of the 4-methoxybenzyl groups
by acetyl groups and removal of the 3a-O-allyl group afforded as 3a-O-unprotected acceptor
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. Ž
.
thexyldimethylsilyl 2,3,4-tri-O-acetyl-a-L-fucopyranosyl - 1™4 -S-6-O-acetyl-2-O-benzoyl-
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.
4-thio-b-D-glucopyranoside 19 , which gave with 2,3,4,6-tetra-O-acetyl-a-D-galactopyrano-
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.
syl trichloroacetimidate as galactosyl donor 20 the trisaccharide. Transformation into a
trichloroacetimidate as glycosyl donor, glycosylation of heptylmercaptan, and then removal of
the O-acyl protective groups afforded target molecule 2. q 1998 Elsevier Science Ltd. All
rights reserved.
Keywords: S-Glycosylation; Base-promoted; Acid catalyzed; S-Glycosides; Anomeric S-alkylation; Glycosyl
trichloroacetimidates; Lewis A analogues; Oligosaccharides, thio; Carbohydrates
w x
1. Introduction
oxygen compounds 9 ; yet thio-linked analogues may
exhibit similar epitope character in biological investi-
gations.
The main antigens of the Lewis blood group sys-
tem found in erythrocytes are Lewis A Le ; Scheme
a
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The retrosynthesis of 2 in Scheme 1 shows that
thio-linked disaccharide A is an essential building
block, which should be available from fucosyl donor
C and 4-thio-glucoside D. Thus, D-galactose will not
only provide galactosyl donor B but also—via a
4-O-unprotected derivative—building block D.
b
.
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. w x
1, 1 and Lewis B Le 2 . Both epitopes were also
detected in the plasma and in numerous secretions
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3 . In the course of our investigations on sulfur-lin-
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x
ked oligosaccharides 4–8 we concentrated also on
the synthesis of partially thio-linked Lea-analogue 2
because thioglycosides are generally more stable to
glycosidase action than the corresponding natural
2. Results and discussion
) Corresponding author.
Glycosylimidates, Part 79. For Part 78, see Ref. 1 .
The lability of totally O-benzyl-protected fucopy-
ranosyl residues towards acid-catalyzed hydrolytic
1
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0008-6215r98r$19.00 q 1998 Elsevier Science Ltd All rights reserved.

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T. Eisele et al.rCarbohydrate Research 306 1998 81–91
Scheme 1.
w
x
cleavage 10 was the reason to introduce a 3,4-O-di-
O-acetyl-2-O-benzyl-protected fucose derivative,
which could be readily attached to acceptors via the
corresponding trichloroacetimidate as glycosyl donor
moved by treatment with Wilkinson’s catalyst and
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x
then with aqueous acid 12 to furnish 1-O-unpro-
tected derivative 7 as arb-mixture. Treatment of 7
with trichloro-acetonitrile in the presence of 1,8-di-
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x
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x
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.
11 . Because hydrogenolytic cleavage of benzyl
groups is generally not compatible with sulfur link-
azabicyclo 5.4.0 -undec-7-ene DBU as base af-
forded the desired fucosyl donor 8 in 95% yield.
The synthesis of the 4-thio-glucose building block
D was based on known thexyldimethylsilyl 4,6-O-
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ages, we generated the corresponding 2-O- 4-metho-
xyphenylmethyl MPM -protected fucosyl donor 8
as building block C Scheme 2 ; based on compara-
tive studies, oxidative cleavage of the MPM group in
the presence of sulfur linkages seemed to be possible
. Ž
.
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.
w
x
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.
benzylidene-D-galactoside 9 7,13 Scheme 3 . Re-
gioselective 3-O-allylation of 9 by treatment firstly
with dibutyltin oxide Bu2SnO 14,15
with allyl bromide in the presence of tetrabutylam-
monium bromide TBABr furnished compound 10 in
good yield. Benzoylation with benzoyl chloride in
pyridine ™11 followed by hydrolytic removal of
2
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.
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x
and then
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8 . Compound 8 was readily obtained from allyl
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.
3,4-O-isopropylidene-fucopyranoside 3, which is
gained in a one-pot procedure from L-fucose. Treat-
ment of 3 with 4-methoxyphenylmethyl chloride in
the presence of sodium hydride in N,N-dimethyl-
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.
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.
formamide ™4 , acid-catalyzed removal of the O-
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.
2 1-O-Thexyldimethylsilyl protection was chosen be-
isopropylidene group ™5 , and then O-acetylation
with acetic anhydride in pyridine afforded allyl fuco-
side 6 in very high yield. The allyl group was re-
cause sulfur-containing substrates interfere with tin com-
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pounds; see Ref. 15 .

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T. Eisele et al.rCarbohydrate Research 306 1998 81–91
83
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.
the benzylidene group and then regioselective intro-
16 in high yield Scheme 4 . For the cleavage of the
two 4-methoxyphenylmethyl groups, which had ful-
filled their task, a mild oxidizing agent was required.
duction of the 4-methoxyphenylmethyl group at O-6
1
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x
by treatment with dibutyltin oxide 14,15 and then
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.
with 4-methoxyphenylmethyl chloride in the presence
Dichlorodicyanobenzoquinone DDQ in water con-
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.
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of tetrabutylammonium iodide TBAI led to 4-O-un-
protected galactose derivative 13 in high yield; 13 is
a unique building block because it offers selective
access to each of the hydroxy groups. The critical
taining dichloromethane 16 proved to be ideal; it
furnished 6a,2b-O-unprotected thiodisaccharide 17 in
high yield. Acetylation with acetic anhydride in pyri-
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.
dine ™18 and then removal of the 3a-O-allyl
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introduction of the thiol group 4,5 was performed
via nucleophilic substitution; thus 13 was trans-
formed into the 4-O-trifluoromethanesulfonate by
treatment with trifluoromethanesulfonic anhydride
group by subsequent treatment with zinc chloride,
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.
tetrakis triphenylphosphine palladium and then with
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triethylsilane 17 afforded 3a-O-unprotected acceptor
19, representing building block A, in high yield.
Glycosylation of acceptor 19 with known galacto-
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.
Tf2O in the presence of pyridine at 0 8C and then
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with potassium thioacetate in N,N-dimethylform-
amide to afford 4-S-acetyl-4-thioglucoside 14; selec-
tive removal of the S-acetyl group could be readily
accomplished with sodium methanolate in methanol
to give acceptor 15.
Acid-catalyzed glycosylation of 15 with glycosyl
donor 8 in the presence of trimethylsilyl triflate as
catalyst gave the desired a-linked thiodisaccharide
syl donor 20 4 as building block B afforded with
0.02 equiv. of trimethylsilyl triflate as catalyst practi-
cally exclusively ortho-ester derivative 22, as indi-
cated by the H NMR data d 1.70; s, 3 H, O3CCH3 ;
however, when this reaction was carried out with
0.04 equiv. of trimethylsilyl triflate the desired Lea-
building block 21 was obtained in 70% yield. Re-
moval of the thexyldimethylsilyl TDS group by
treatment with tetrabutylammonium fluoride TBAF
1
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.
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.
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.
in the presence of acetic acid furnished 1-O-unpro-
tected trisaccharide 23, which gave with trichloroace-
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tonitrile in the presence of 1,8-diazabicyclo 5.4.0 un-
dec-7-ene as base the desired glycosyl donor 24. Acid
catalyzed S-glycosylation of heptylmercaptan in the
presence of trimethylsilyl triflate as catalyst led to
thioglycoside 25 in practically quantitative yield.
Treatment of 25 with sodium methanolate in methanol
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w x.
Zemplen conditions 18 provided target molecule
´
2. The anomeric configurations could be readily de-
rived from the H NMR data: 25: d 4.39 d, J1a,2a
10.1 Hz, H-1a , 4.65 d, J1b,2b 8.1 Hz, H-1b , 5.60
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H-1a , 4.77 d, J1b,2b 7.4 Hz, H-1b , 5.49 d, J1c,2c
4.8 Hz, H-1c .
1
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.
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.
.
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.
d, J1c,2c 4.3 Hz, H-1c ; 2: d 4.35 d, J1a,2a 10 Hz,
.
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.
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3. Experimental
General.—Melting points are uncorrected values.
1H NMR spectra were recorded on Bruker AC 250
Cryospec and Bruker DRX 600 instruments. Optical
rotations were performed with Perkin–Elmer po-
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.
larimeter 241 MC 1-dm cell . TLC was carried out
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.
with plastic sheets, Silica Gel 60F254 Merck , and
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detection was done by UV light 254 nm or by
spraying with 5% ammonium molybdate and 0.1%
cerium sulfate in 10% H2SO4 and heating to 120 8C.
Flash chromatography was carried out with Silica Gel
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.
60 Baker, particle size 40 mm .
Scheme 2.

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T. Eisele et al.rCarbohydrate Research 306 1998 81–91
Scheme 3.
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Allyl 3,4-O-isopropylidene-a-L-fucopyranoside 3 .
—L-Fucose 40 g, 243.7 mmol was suspended in dry
.
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.
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.
OH , 1.52 s, 3 H, CH3 , 1.35 s, 3 H, CH3 ,
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.
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1.33–1.30 d, 3 H, J5,6 6.3 Hz, CH3 . Anal. Calcd
for C12 H20O5 244.28 : C, 59.00; H, 8.25. Found: C,
58.86; H, 8.17.
Allyl 3,4-O-isopropylidene-2-O-p-methoxybenzyl-a-
L-fucopyranoside 4 .—To a solution of compound 3
38.6 g, 158.7 mmol in dry Me2 NCHO 350 mL
Ž
were added p-methoxybenzyl bromide 25 mL, 184.4
mmol and NaH 4.55 g, 189.9 mmol at 0 8C. After
stirring for 30 min at room temperature, MeOH 10
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.
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.
allyl alcohol 1 L and then boiled under reflux in the
q
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.
presence of Amberlite IR 120 H form . After 4 h,
the ion-exchange resin was separated by filtration and
the solution concentrated in vacuo. The residue was
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.
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.
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.
suspended in dry acetone 1.3 L and then p-
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.
toluenesulfonic acid 700 mg, 3.64 mmol added.
After stirring for 2 h the reaction mixture was neu-
tralized with triethylamine and then concentrated in
.
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.
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.
vacuo. Flash chromatography 5:2 light petroleum–
mL was added to destroy excess base. The reaction
.
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.
.
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mixture was diluted with water 350 mL and ex-
EtOAc afforded 3 38.64 g, 65% as colourless oil;
TLC 1:1 light petroleum–EtOAc : Rf 0.38; a
y1288 c 1, CHCl3 ; H NMR 250 MHz, CDCl3 :
d 5.97–5.86 m, 1 H, CH2–CH5CH2 , 5.33–5.19
m, 2 H, CH2–CH5CH2 , 4.87 d, 1 H, J1,2 3.9 Hz,
H-1 , 4.29–4.01 m, 5 H, H-3,4,5 and CH2–
CH5CH2 , 3.84–3.76 ddd, 1 H, J1,2 3.9, J2,3 6.9,
Ž
w x
Ž .
tracted with Et2O 3=150 mL . The organic extract
D
.
1
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.
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was washed with water 3=200 mL , dried MgSO4 ,
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.
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and evaporated in vacuo. Flash chromatography 6:1
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.
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.
™5:1 light petroleum–EtOAc yielded compound 4
.
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.
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52.5 g, 91% as a colourless oil; TLC 2:1 light
. w x Ž
petroleum–EtOAc : Rf 0.60; a y96.28 c 1.0,
1
.
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D
.
Ž
. Ž .
CHCl3 ; H NMR 250 MHz, CDCl3 : d 7.31–7.24
J2,OH 6.9 Hz, H-2 , 2.31–2.28 d, 1 H, J2,OH 6.9 Hz,

(
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T. Eisele et al.rCarbohydrate Research 306 1998 81–91
85
Scheme 4.
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.
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.
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Allyl 2-O-p-methoxybenzyl-a-L-fucopyranoside 5 .
—A solution of 4 50 g, 137.2 mmol in aqueous
m, 2 H, Ph , 6.87–6.81 m, 2 H, Ph , 5.95–5.81 m,
.
Ž
Ž .
1 H, CH2–CH5CH2 , 5.34–5.15 m, 2 H, CH2–
CH5CH2 , 4.72 d, 1 H, J1,2 3.6 Hz, H-1 , 4.65 and
4.56 2 d, each 1 H, Jgem 12.3 Hz, CH2 Ph , 4.29 dd,
1 H, J2,3 7.9, J3,4 5.5 Hz, H-3 , 4.17–3.91 m, 4 H,
CH2–CH5CH2 and H-4,5 , 3.77 s, 3 H, OCH3 ,
3.47 dd, 1 H, J1,2 3.6, J2,3 8 Hz, H-2 , 1.39 and
1.32 2 s, each 3 H, 2 CH3 , 1.29 d, 3 H, J5,6 6.7
Hz, 3 H-6 . Anal. Calcd for C20H28O6 364.44 : C,
.
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.
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.
70% HOAc 250 mL is heated at 40 8C for 6 h. The
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.
Ž
mixture was then concentrated in vacuo and purified
.
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by flash chromatography 1:1 ™ 1:3 light
.
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.
. Ž .
petroleum–EtOAc to give 5 42.7 g, 96% as an
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.
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amorphous, colourless mass; TLC 1:2 light
. w x Ž
petroleum–EtOAc : Rf 0.29; a y115.38 c 1.0,
1
.
Ž
D
.
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.
. Ž .
CHC13 ; H NMR 250 MHz, CDCl3 : d 7.27–7.22
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.
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.
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65.91; H, 7.74. Found: C, 65.87; H, 7.67.
m, 2 H, Ph , 6.88–6.82 m, 2 H, Ph , 5.97–5.81 m,

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86
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
.
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.
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.
1 H, CH2–CH5CH2 , 5.34–5.16 m, 2 H, CH2–
7.27–7.19 m, 2 H, Ph , 6.88–6.81 m, 2 H, Ph ,
.
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.
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.
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CH5CH2 , 4.81 d, 1 H, J1,2 3.5 Hz, H-1 , 4.58 and
4.51 2 d, each 1 H, Jgem 11.6 Hz, CH2 Ph , 4.16–3.88
m, 4 H, H-3,5 and CH2–CH5CH2 , 3.79–3.78 m,
4 H, H-4 and OCH3 , 3.66 dd, 1 H, J1,2 3.5, J2,3
9.9 Hz, H-2 , 2.50 s, 1 H, OH , 2.35 s, 1 H, OH ,
1.25 d, 3 H, J5,6 6.6 Hz, 3 H-6 . Anal. Calcd for
C17H24O6 324.37 : C, 62.95; H, 7.46. Found: C,
5.28 dd, 1 H, J3,4 3.5, J4,5 -1 Hz, H-4 , 4.93 dd, 1
H, J2,3 10.2, J3,4 3.5 Hz, H-3 , 4.72 dd, 1 H, J1,OH
1.9, J1,2 7.7 Hz, H-1 , 4.64–4.55 m, 2 H, CH2 Ph ,
4.33 dq, 1 H, J4,5 -1, J5,6 6.5 Hz, H-5 , 3.77 s, 3
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.
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.
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.
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.
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.
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.
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.
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.
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H, OCH3 , 3.54 dd, 1 H, J1,2 7.7, J2,3 10.2 Hz,
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.
.
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.
H-2 , 3.07 d, 1 H, J1,OH 1.9 Hz, OH , 1.99 and 1.96
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.
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.
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2 s, each 3 H, 2 Ac , 1.09 d, 3 H, J5,6 6.5 Hz, 3
H-6 . Anal. Calcd for C18H24O8 368.38 : C, 58.69;
H, 6.57. Found: C, 58.63; H, 6.86.
3, 4-Di-O-acetyl-2-O- 4-methoxybenzyl -a-L -
fucopyranosyl trichloroacetimidate 8 .—To a solu-
tion of 7 32.4 g, 87.9 mmol in CH2Cl2 350 mL
were added trichloroacetonitrile 90 mL, 880 mmol
and 1,8-diazabicyclo 5.4.0 undec-7-ene 330 mL, 2.2
mmol . After 30 min, the mixture was concentrated
in vacuo. Flash chromatography of the residue 3:2
light petroleum–EtOAc yielded 8 42.84 g, 95% in
the ratio a:bs6:1 as a colorless foam. Repeated
treatment of the anomeric mixture with trichloroace-
tonitrile and 1,8-diazabicyclo 5.4.0 undec-7-ene con-
verted the b-trichloroacetimidate into pure a-anomer.
Compound 8 could be crystallized from Et2O. TLC
3:2 light petroleum–EtOAc : Rf 0.52; mp 133–134
8C; a y69.98 c 1.0, CHCl3 ; H NMR 250
MHz, CDCl3 : d 8.57 s, 1 H, NH , 7.21–7.17 m, 2
H, Ph , 6.86–6.80 m, 2 H, Ph , 6.45 d, 1 H, J1,2 3.6
Hz, H-1 , 5.34–5.29 m, 2 H, H-3,4 , 4.57 2 d, each
1 H, Jgem 11.6 Hz, CH2 Ph , 4.31 dq, 1 H, J4,5 -1,
J5,6 6.6 Hz, H-5 , 3.97 dd, 1 H, J1,2 3.6, J2,3 9.8 Hz,
.
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.
62.65; H, 7.40.
(
)
Allyl 3,4-di-O-acetyl-2-O- 4-methoxybenzyl -a-L-
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Ž
(
)
fucopyranoside 6 .—Compound 5 42 g, 129.5
.
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.
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mmol was stirred in 1:1 pyridine–Ac2O 200 mL at
room temperature for 18 h. Concentration of the
mixture in vacuo and purification of the residue by
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.
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.
.
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w
x
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flash chromatography 7:2™5:2 light petroleum–
.
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.
.
EtOAc yielded 6 52.8 g, quantitative as a colour-
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.
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.
less oil; TLC 4:1 light petroleum–EtOAc : Rf 0.16;
1
w x
a
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.
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y61.48 c 1.0, CHCl3 ; H NMR 250 MHz,
D
.
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.
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CDCl3 : d 7.24–7.20 m, 2 H, Ph , 6.87–6.81 m, 2
.
Ž
Ž
.
H, Ph , 5.96–5.81 m, 1 H, CH2–CH5CH2 , 5.33–
5.16 m, 4 H, H-3,4 and CH2CH5CH2 , 4.79 d, 1
H, J1,2 3.6 Hz, H-1 , 4.61 and 4.49 2 d, each 1 H,
.
Ž
w
x
.
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.
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Jgem 11.9 Hz, CH2 Ph , 4.17–3.92 m, 3 H, H-5 and
.
Ž
Ž
.
CH2–CH5CH2 , 3.79 dd, 1 H, J1,2 3.6, J2,3 10.3
Hz, H-2 , 3.78 s, 3 H, OCH3 , 2.11 and 1.97 2 s,
each 3 H, 2 Ac , 1.07 d, 3 H, J5,6 6.6 Hz, 3 H-6 .
Anal. Calcd for C21H28O8 408.45 : C, 61.75; H,
6.91. Found: C, 61.73; H, 6.99.
3,4-Di-O-acetyl-2-O- 4-methoxybenzyl -arb-L-
fucopyranose 7 .—To a solution of 6 52.5 g, 128.53
1
.
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.
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w x
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.
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D
.
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.
.
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.
Ž
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.
.
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.
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.
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.
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(
)
.
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.
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.
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.
.
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.
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mmol in 9:1 EtOH–water 1200 mL were added
H-2 , 3.77 s, 3 H, OCH3 , 2.13 and 1.98 2 s, each 3
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.
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.
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.
tris triphenylphosphine rhodium I chloride 600 mg,
H, 2 Ac , 1.12 d, J5,6 6.6 Hz, 3 H, 3 H-6 . Anal.
.
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x
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.
649 mmol and 1,8-diazabicyclo 5.4.0 undec-7-ene
2.4 mL, 16 mmol . The reaction mixture was heated
Calcd for C20H24Cl3NO8 512.77 : C, 46.85; H,
4.72; N, 2.73. Found: C, 46.91; H, 4.72; N, 2.69.
Thexyldimethylsilyl 3-O-allyl-4,6-O-benzylidene-b-
d-galactopyranoside 10 .—A mixture of compound
9 7,13 2.1 g, 5.11 mmol and dibutyltin oxide 1.4
g, 5.6 mmol in dry toluene 100 mL was heated at
reflux for 18 h in an apparatus for the continuous
removal of water. The solution was then concentrated
to two-thirds of its original volume by continued
evaporation, cooled to 60 8C and allyl bromide 4.4
mL, 51.1 mmol and Bu4NBr 1.82 g, 5.6 mmol
were added. After 18 h at 60 8C, the reaction mixture
was concentrated in vacuo. Flash chromatography
4:1 light petroleum–EtOAc of the residue yielded
10 1.4 g, 62% as a colourless oil; TLC 4:1 light
petroleum–EtOAc : Rf 0.2;
CHCl3 ; H NMR 250 MHz, CDCl3 : d 7.51–7.29
m, 5 H, Ph , 6.00–5.86 m, 1 H, CH5CH2 , 5.50
s, 1 H, C H Ph , 5.34–5.15 m, 2 H, CH5CH2 ,
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.
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.
to reflux temperature bath temperature 90 8C for 1
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.
h, filtered, and evaporated in vacuo. The oily residue
was redissolved in 2:1 acetone–1 M HCl 1200 mL
and stirred for 32 h at room temperature. The reaction
mixture was extracted with EtOAc 3=300 mL ,
washed with saturated aqueous NaHCO3 3=150
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.
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x
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.
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.
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.
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mL and dried MgSO4 . Purification of the residue
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by flash chromatography 3:2 ™ 4:3 light
.
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.
.
Ž
.
petroleum–EtOAc yielded 7 35.5 g, 75% in the
Ž
ratio a:bs1:1 as an inseparable mixture; TLC 3:2
.
w x
Ž
light petroleum–EtOAc : Rf 0.21; a y37.68 c
D
1
.
Ž
.
.
Ž
.
1.0, CHCl3 ; H NMR 250 MHz, CDCl3 : 7a: d
Ž
Ž
.
Ž
.
Ž
7.27–7.19 m, 2 H, Ph , 6.88–6.81 m, 2 H, Ph ,
5.28–5.17 m, 2 H, H-3,4 , 4.75 dd, 1 H, J1,OH 5.4,
J1,2 3.6 Hz, H-1 , 4.64–4.55 m, 2 H, CH2 Ph ,
3.80–3.73 m, 5 H, H-2,5 and OCH3 , 3.46 d, 1 H,
J1,OH 5.4 Hz, OH , 2.13 and 2.12 2 s, each 3 H, 2
Ac , 1.17 d, 3 H, J5,6 6.4 Hz, 3 H-6 . 7b: d
Ž
.
Ž
Ž
.
w x
Ž
a
q28.98 c 0.3,
D
1
.
.
.
Ž
.
Ž
.
Ž
Ž
Ž
.
Ž
.
.
Ž
.
Ž
.
.
Ž
.
Ž
.
Ž
4.55 d, 1 H, J1,2 7.4 Hz, H-1 , 4.24 dd, 1 H, J5,6

(
)
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
87
.
Ž
X
.
Ž
.
Ž
.
1.5, J6,6 12.3 Hz, H-6 , 4.21–4.17 m, 3 H, H-4 and
H-3,5 , 2.08 bs, 2 H, OH , 1.52–1.41 m, 1 H, CH ,
.
Ž
Ž
X
X
Ž
.
CH2–CH5CH2 , 4.03 dd, 1 H, J5,6 1.9, J6,6 12.3
Hz, H-6 , 3.83 dd, 1 H, J1,2 7.4, J2,3 9.8 Hz, H-2 ,
3.42 dd, 1 H, J2,3 9.8, J3,4 3.6 Hz, H-3 , 3.37–3.36
m, 1 H, H-5 , 1.70–1.59 m, 1 H, CH , 0.89, 0.88,
0.69, 0.68, 0.67, and 0.66 4 s, each 3 H, 4 CH3 ,
0.12 and 0.03 2 s, each 3 H, SiMe2 . Anal. Calcd for
C24H38O7Si 466.65 : C, 61.77; H, 8.21. Found: C,
61.62; H, 8.32.
Thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-6-O- 4-
methoxybenzyl - b - D - galactopyranoside 13 .—A
mixture of compound 12 16.6 g, 35.47 mmol and
Bu2SnO 9.71 g, 39 mmol in dry toluene 500 mL
X
.
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
(
0.87 and 0.86 4 s, each 3 H, 4 CH3 , 0.20 and 0.17
Ž
Ž
.
)
Ž
.
2 s, each 3 H, SiMe2 . Anal. Calcd for C24H38O6Si
.
Ž
.
450.65 : C, 63.97; H, 8.50. Found: C, 63.95; H,
Ž
.
Ž
.
8.63.
Thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-4,6-O-
Ž
.
benzylidene-b-D-galactopyranoside 11 .—A solution
Ž
.
Ž
of compound 10 1 g, 2.21 mmol in dry pyridine 20
mL was treated with benzoyl chloride 386 mL, 3.33
mmol at room temperature. After stirring for 18 h,
the reaction mixture was poured into ice water 30
mL and extracted with EtOAc 2=30 mL . The
organic layer was washed with water 2=20 mL
.
Ž
.
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
and with saturated NaCl 2=20 mL , dried MgSO4 ,
and concentrated in vacuo. Flash chromatography
Ž
.
Ž
35:1 toluene–acetone of the residue yielded 11 109
.
.
Ž
g, 89% as a colourless syrup; TLC 35:1 toluene–
1
w x
Ž
.
acetone : Rf 0.25; a q35.48 c 1.0, CHCl3 ; H
D
Ž
.
Ž
.
NMR 250 MHz, CDCl3 : d 8.05–8.01 m, 2 H, Ph ,
Ž
.
Ž
7.57–7.31 m, 8 H, Ph , 5.84–5.69 m, 1 H, CH2–
CH5CH2 , 5.55 s, 1 H, CHPh , 5.52 dd, 1 H, J1,2
7.6, J2,3 10.2 Hz, H-2 , 5.23–5.04 m, 2 H, CH2–
CH5CH2 , 4.84 d, 1 H, J1,2 7.6 Hz, H-1 , 4.31–4.27
m, 2 H, H-4,6 , 4.16–4.00 m, 3 H, CH2–CH5CH2
and H-3,6 , 3.69 dd, 1 H, J2,3 10.2, J3,4 3.6 Hz,
H-3 , 3.44–3.43 m, 1 H, H-5 , 1.55–1.44 m, 1 H,
CH , 0.71, 0.70, 0.69, and 0.68 4 s, each 3 H, 4
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
X
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
CH3 , 0.16 and 0.07 2 s, each 3 H, SiMe2 . Anal.
Ž
.
Calcd for C31H42O7Si 554.76 : C, 67.12; H, 7.63.
Found: C, 67.23; H, 7.61.
Thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-b-D-
66.11; H, 8.18.
Ž
.
Ž
galactopyranoside 12 .—Compound 11 1 g, 1.8
Thexyldimethylsilyl 4-S-acetyl-3-O-allyl-2-O-
.
Ž
.
(
)
mmol was dissolved in CH2Cl2 35 mL and aque-
ous 50% CF3CO2 H 7 mL . After being stirred for 3
h at room temperature, the mixture was diluted with
CH2Cl2 25 mL , washed with saturated aqueous
NaHCO3 2=20 mL , dried MgSO4 , and evapo-
rated in vacuo. The residue was purified by flash
chromatography 4:1 toluene–acetone to give 12
781 mg, 93% as an amorphous mass; TLC 1:1
light petroleum–EtOAc : Rf 0.27; a y60.28 c
0.5, CHCl3 ; H NMR 250 MHz, CDCl3 : d 8.04–
8.00 m, 2 H, Ph , 7.58–7.39 m, 3 H, Ph , 5.78–5.64
m, 1 H, CH2–CH5CH2 ,5.36 dd, 1 H, J1,2 7.7,
benzoyl - 6 - O - 4 - methoxybenzyl - 4 - thio - b - D -
Ž
.
Ž
.
glucopyranoside 14 .—A solution of compound 13
Ž
.
Ž
.
18.7 g, 31.92 mmol in CH2Cl2 300 mL and
pyridine 10.5 mL was treated at 0 8C with trifluo-
romethanesulfonic anhydride 8.4 mL, 51.1 mmol ,
stirred for 1 h at 0 8C and for 30 min at room
temperature. The reaction mixture was diluted with
Ž
Ž
.
Ž
.
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
Ž
.
CH2Cl2 200 mL and washed with saturated aque-
.
Ž
w x
Ž
Ž
.
.
ous NaHCO3 2=150 mL . The organic layer was
dried MgSO4 , filtered, and evaporated in vacuo.
The residue was redissolved in dry Me2 NCHO 200
mL and treated for 1 h with potassium thioacetate
D
1
.
.
Ž
Ž
.
Ž
.
Ž
Ž
.
Ž
.
.
Ž
Ž
.
J2,3 9.8 Hz, H-2 , 5.21–5.06 m, 2 H, CH2–
7.5 g, 65.7 mmol at room temperature. The reaction
.
Ž
.
CH5CH2 , 4.76 d, 1 H, J1,2 7.7 Hz, H-1 , 4.14–3.95
m, 4 H, H-4,6 and CH2–CH5CH2 , 3.81 dd, 1 H,
J5,6 4.6, J6,6 11.6 Hz, H-6 , 3.63–3.55 m, 2 H,
mixture was concentrated in vacuo, redissolved in
Ž
.
Ž
Ž
Ž
.
Ž
.
EtOAc 300 mL , washed with water 3=100 mL ,
X
.
X
X
Ž
.
dried MgSO4 , and evaporated in vacuo. Flash chro-

(
)
88
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
Ž
.
Ž
.
Ž
matography 50:1 toluene–EtOAc of the residue
5.81–5.65 m, 1 H, CH2–CH5CH2 , 5.59 d, 1 H,
Ž
.
.
Ž
.
yielded 14 10.6 g, 52% as a colourless syrup; TLC
50:1 toluene–EtOAc : Rf 0.15; a q2.08 c 0.3,
CHCl3 ; H NMR 250 MHz, CDCl3 : d 8.03–7.99
m, 2 H, Ph , 7.57–7.14 m, 5 H, Ph , 6.87–6.82 m,
2 H, Ph , 5.75–5.61 m, 1 H, CH2–CH5CH2 , 5.17
dd, 1 H, J1,2 7.7, J2,3 9.1 Hz, H-2 , 5.09–4.93 m, 2
H, CH2–CH5CH2 , 4.75 d, 1 H, J1,2 7.7 Hz, H-1 ,
J1b,2b 5.5 Hz, H-1b , 5.18–5.13 m, 3 H, H-2a,3b,4b ,
Ž
.
w x
Ž
Ž
.
Ž
5.11–5.08 m, 1 H, CH2–CH5CH2 , 4.98–4.96 m,
D
1
.
Ž
.
.
Ž
1 H, CH2–CH5CH2 , 4.69 d, 1 H, J1a,2a 7.7 Hz,
H-1a , 4.59–4.56 m, 2 H, H-5b and CH2 Ph , 4.51
d, 1 H, J 12 Hz, CH2 Ph , 4.46 d, 1 H, J 11.4 Hz,
CH2 Ph , 4.35 d, 1 H, J 11.4 Hz, CH2 Ph , 4.23–4.20
m, 1 H, CH2–CH5CH2 , 4.11–4.08 m, 1 H, CH2–
CH5CH2 , 3.99 dd, 1 H, J1b,2b 5.5, J2b,3b 10.3 Hz,
H-2b , 3.86 dd, 1 H, J5a,6a 4.5, J6a,6 a 11.1 Hz,
H-6a , 3.78–3.74 m, 7 H, H-6 a and 2 OCH3 , 3.55
m, 1 H, H-5a , 3.42 dd, 1 H, J2a,3a sJ3a,4a s10.7
Hz H-3a , 3.06 dd, 1 H, J3a,4a 10.7, J4a,5a 11 Hz,
H-4a , 2.11 and 1.95 2 s, each 3 H, 2 Ac , 1.51–1.42
m, 1 H, CH , 1.05 d, 3 H, J5b,6b 6.4 Hz, 3 H-6b ,
0.71, 0.70, 0.69, and 0.68 4 s, each 3 H, 4 CH3 ,
0.12 and 0.01 2 s, each 3 H, SiMe2 . Anal. Calcd for
C50H68O14SSi 953.23 : C, 63.00; H, 7.19. Found:
C, 63.02; H, 7.26.
Ž
.
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
.
Ž
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
.
Ž
X
Ž
.
Ž
.
Ž
4.48 s, 2 H, CH2 Ph , 4.10–3.60 m, 9 H, H-3,5,6,6 ,
OCH3, and CH2–CH5CH2 , 3.51 dd, 1 H, J3,4
.
Ž
.
Ž
X
s
X
.
Ž
.
.
Ž
.
J4,5 s10.8 Hz, H-4 , 2.30 s, 3 H, Ac , 1.52–1.41
Ž
.
Ž
Ž
.
Ž
m, 1 H, CH , 0.69, 0.68, 0.67, and 0.66 4 s, each 3
.
Ž
.
.
Ž
H, 4 CH3 , 0.13 and 0.03 2 s, each 3 H, SiMe2 .
Anal. Calcd for C34H48O8SSi 644.90 : C, 63.32; H,
7.50. Found: C, 62.70; H, 7.53.
Thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-6-O- 4-
methoxybenzyl -4-thio-b-D-glucopyranoside 15 .—To
a solution of compound 14 10.4 g, 16.13 mmol in
Ž
.
.
Ž
Ž
.
Ž
.
.
(
Ž
.
)
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
dry MeOH 200 mL was added 1 M NaOMe in
Ž
.
(
MeOH 17 mL, 17 mmol . The resulting mixture was
stirred for 20 min at room temperature and then
neutralized with Amberlite IR 120 H resin. The
solvent was evaporated to give compound 15 9.72 g,
quantitative as a colourless oil. The crude product
was used for the next step without further purifica-
tion. TLC 20:1 toluene–EtOAc : Rf 0.39; H NMR
250 MHz, CDCl3 : d 8.02–7.99 m, 2 H, Ph ,
7.56–7.23 m, 5 H, Ph , 6.88–6.82 m, 2 H, Ph ,
5.83–5.68 m, 1 H, CH2–C H5CH2 , 5.16–4.97 m,
3 H, H-2 and CH2–CH5CH2 , 4.72 d, 1 H, J1,2 7.7
Hz, H-1 , 4.56 d, 1 H, J 11.7 Hz, CH2 Ph , 4.48 d,
1 H, J 11.7 Hz, CH2 Ph , 4.20–3.40 m, 9 H,
H-3,5,6,6 , OCH3, and CH2–CH5CH2 , 3.09 dd, 1
H, J3,4 sJ4,5 s10.4 Hz, H-4 , 1.80 s, 1 H, SH ,
1.50–1.39 m, 1 H, CH , 0.68, 0.67, 0.66 and 0.65 4
Thexyldimethylsilyl 3, 4 - di - O - acetyl - a - L -
) (
)
fucopyranosyl - 1™4 -S-3-O-allyl-2-O-benzoyl-4-thio-
q
Ž
.
Ž
.
.
b-D-glucopyranoside 17 .—To a solution of com-
Ž
Ž
Ž
.
pound 16 5 g, 5.24 mmol in CH2Cl2 108 mL and
water 6 mL was added 2,3-dichloro-5,6-dicyano-p-
benzoquinone 3.1 g, 13.66 mmol at room tempera-
ture. After stirring overnight, the mixture was diluted
with CH2Cl2 50 mL and washed with saturated
aqueous NaHCO3 2=50 mL and with water 5=
50 mL . The organic layer was dried MgSO4 , fil-
tered, and evaporated in vacuo. Flash chromatogra-
.
Ž
.
Ž
.
1
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
Ž
.
Ž
Ž
.
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
.
Ž
Ž
Ž
.
.
Ž
phy 6:1™4:1 toluene–acetone yielded 17 3.3 g,
.
Ž
88% as a colourless foam; TLC 4:1 toluene–
X
1
.
Ž
.
w x
Ž
.
acetone : Rf 0.23; a y84.08 c 0.3, CHCl3 ; H
NMR 250 MHz, CDCl3 : d 8.03–8.00 m, 2 H, Ph ,
D
.
Ž
.
Ž
Ž
.
Ž
.
Ž
.
Ž
.
Ž
7.59–7.40 m, 3 H, Ph , 5.79–5.65 m, 1 H, CH2–
.
Ž
.
Ž
.
s, each 3 H, 4 CH3 , 0.11 and 0.01 2 s, each 3 H,
CH5CH2 , 5.60 d, 1 H, J1b,2b 5.4 Hz, H-1b ,
.
Ž
.
SiMe2 .
5.21–4.96 m, 5 H, H-2a,3b,4b and CH2CH5CH2 ,
[
(
Ž
.
Ž
Thexyldimethylsilyl 3, 4 - di - O - acetyl - 2 - O - 4 -
4.77 d, 1 H, J1a,2a 7.7 Hz, H-1a , 4.46 dq, 1 H,
J4b,5b 1, J5b,6b 6.4 Hz, H-5b , 4.31–3.95 m, 5 H,
H-2b,6a,6 a and CH2–CH5CH2 , 3.56–3.47 m, 2
)
] (
)
.
Ž
methoxybenzyl -a-L-fucopyranosyl - 1™4 -S-3-O-
X
(
)
.
Ž
allyl-2-O-benzoyl-6-O- 4-methoxybenzyl -4-thio-b-D-
Ž
Ž
.
Ž
.
Ž
glucopyranoside 16 .—A solution of 15 200 mg,
331 mmol and 8 255 mg, 497 mmol in dry CH2Cl2
4 mL was treated at room temperature with 0.02 M
Me3SiOTf in CH2Cl2 250 mL, 5 mmol . After
stirring for 10 min, the reaction mixture was neutral-
ized with Et3N and concentrated in vacuo. The residue
was purified by flash chromatography 30:1
toluene–acetone to give 16 237 mg, 75% as a
H, H-3a,5a , 3.12 dd, 1 H, J3a,4a sJ4a,5a s10.9 Hz,
.
.
.
Ž
.
Ž
H-4a , 2.30 d, 1 H, J 7.9 Hz, OH , 2.13 and 2.03 2
Ž
.
.
Ž
.
Ž
s, each 3 H, 2 Ac , 1.51–1.41 m, 1 H, CH , 1.09 d,
3 H, J 6.4 Hz, 3 H-6b , 0.69, 0.68, 0.67 and 0.66 4
s, each 3 H, 4 CH3 , 0.09 and 0.01 2 s, each 3 H,
SiMe2 . Anal. Calcd for C34H52O12SSi 712.93 : C,
Ž
.
.
Ž
.
Ž
.
Ž
.
Ž
57.28; H, 7.35. Found: C, 57.48; H, 7.39.
.
Ž
.
(
Thexyldimethylsilyl 2, 3, 4 - tri - O - acetyl - a - L -
Ž
) (
)
colourless, amorphous mass; TLC 30:1 toluene–
acetone : Rf 0.26; a y91.28 c 0.3, CHCl3 ; H
NMR 250 MHz, CDCl3 : d 8.03–8.00 m, 2 H, Ph ,
fucopyranosyl - 1™4 -S-6-O-acetyl-3-O-allyl-2-O-
1
.
w x
Ž
.
Ž
.
benzoyl-4-thio-b-D -glucopyranoside 18 .—Com-
D
Ž
.
.
Ž
.
.
Ž
.
pound 17 3 g, 4.21 mmol was stirred in 1:1 pyri-
Ž
Ž
Ž
.
7.54–7.17 m, 5 H, Ph , 6.85–6.83 m, 2 H, Ph ,
dine–Ac2O 40 mL at room temperature for 4 h.

(
)
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
89
) (
)
[(
)]
Ž
Concentration of the mixture in vacuo and purifica-
fucopyranosyl - 1™4 -S- 2,3,4,6-tetra-O-acetyl-b-D-
Ž
) (
tion of the residue by flash chromatography 20:1
galactopyranosyl - 1™3 -6-O-acetyl-2-O-benzoyl-4-
.
Ž
.
.
w x
toluene–acetone yielded 18 3.32 g, quant as a
thio-b-D-glucopyranoside 21 .—A solution of 20 4
Ž
.
Ž
.
Ž
.
colourless foam; TLC 20:1 toluene–acetone : Rf
1.3 g, 2.64 mmol and 19 1 g, 1.32 mmol in dry
1
w x
Ž
.
Ž
Ž
.
0.20; a y99.38 c 0.3, CHCl3 ; H NMR 250
CH2Cl2 7 mL was treated at room temperature with
D
.
.
Ž
.
Ž
.
MHz, CDCl3 : d 8.02–7.99 m, 2 H, Ph , 7.58–7.40
0.1 M Me3SiOTf in CH2Cl2 1.06 mL, 106 mmol .
After stirring for 30 min, the reaction mixture was
neutralized with Et3N and concentrated in vacuo. The
residue was purified by flash chromatography 3:2
light petroleum–EtOAc to give 21 1 g, 70% as a
Ž
Ž
m, 3 H, Ph , 5.78–5.64 m, 2 H, H-1b and CH2–
CH5CH2 , 5.28–4.97 m, 6 H, H-2a,2b,3b,4b and
CH2–CH5CH2 , 4.68 d, 1 H, J1a,2a 7.7 Hz, H-1a ,
4.59–4.52 m, 2 H, H-5b,6a , 4.23–4.05 m, 3 H,
H-6 a and CH2–CH5CH2 , 3.64–3.58 m, 1 H,
H-5a , 3.43 dd, 1 H, J2a,3a 9.4, J3a,4a 11 Hz, H-3a ,
2.93 dd, 1 H, J3a,4a sJ4a,5a s11 Hz, H-4a , 2.14,
2.08, 2.05 and 1.97 4 s, each 3 H, 4 Ac , 1.50–1.39
m, 1 H, CH , 1.08 d, 3 H, J5b,6b 6.4 Hz, 3 H-6b ,
0.68, 0.67, 0.66 and 0.65 4 s, each 3 H, 4 CH3 ,
0.08 and 0.01 2 s, each 3 H, SiMe2 . Anal. Calcd for
C38H56O14SSi 797.01 : C, 57.27; H, 7.08. Found:
.
Ž
.
Ž
.
Ž
Ž
.
Ž
Ž
.
Ž
.
X
.
Ž
.
colourless foam; TLC 5:4 light petroleum–EtOAc :
1
.
Ž
Ž
.
w x
Ž
.
Ž
Rf 0.20; a D y49.18 c 0.5, CHCl3 ; H NMR 250
.
.
Ž
.
MHz, CDCl3 : d 7.99–7.96 m, 2 H, Ph , 7.59–7.43
Ž
Ž
.
Ž
.
Ž
.
m, 3 H, Ph , 5.61 d, 1 H, J1c,2c 4.1 Hz, H-1c ,
Ž
.
.
.
Ž
.
5.34–4.98 m, 6 H, H-2c,3c,4c,2b,4b,2a , 4.64–4.49
m, 6 H, H-1a,6a,5c,1b,3b,6b , 4.20–4.09 m, 2 H,
H-6 a,6 b , 3.84–3.75 m, 2 H, H-3a,5b , 3.61–3.56
Ž
Ž
.
Ž
X
X
Ž
.
.
Ž
.
Ž
.
Ž
.
Ž
m, 1 H, H-5a , 2.90 dd, 1 H, J3a,4a sJ4a,5a s11 Hz,
.
C, 56.99; H, 7.13.
H-4a , 2.15, 2.14, 2.08, 2.07, 2.05, 1.95, 1.92 and
(
Ž
.
Ž
.
Thexyldimethylsilyl 2, 3, 4 - tri - O - acetyl - a - L -
1.85 8 s, each 3 H, 8 Ac , 1.46–1.36 m, 1 H, CH ,
1.21 d, 3 H, J5c,6c 6.4 Hz, 3 H-6c , 0.66, 0.65, 0.64
and 0.63 4 s, each 3 H, 4 CH3 , 0.06 and y0.05 2
s, each 3 H, SiMe2 . Anal. Calcd for C49H70O23SSi
) (
)
Ž
.
fucopyranosyl - 1™4 -S-6-O-acetyl-2-O-benzoyl-4-
Ž
.
Ž
.
Ž
thio-b-D -glucopyranoside 19 .—To a solution of
Ž
.
.
compound 18 3 g, 3.76 mmol in dry tetrahydrofuran
Ž
.
Ž
Ž
.
70 mL was added dry zinc chloride 1.28 g, 9.41
mmol at room temperature. After stirring for 15 min,
tetrakis triphenylphosphine palladium O
606 mmol was added and after another 10 min
1087.23 : C, 54.13; H, 6.49. Found: C, 53.51; H,
6.50.
Thexyldimethylsilyl 2, 3, 4 - tri - O - acetyl - a - L -
) ( [(
.
Ž
.
Ž .
Ž
(
700 mg,
.
)
fucopyranosyl - 1™4 -S- 3,4,6,-tri-O-acetyl-1,2-
Ž
.
) ( )]
triethylsilane 2.4 mL, 15.1 mmol . After stirring
orthoacetyl-a-D-galactopyranosyloxy - 1™3 -6-O-
Ž
.
overnight in the dark, the mixture was diluted with
acetyl-2-O-benzoyl-4-thio-b-D-glucopyranoside 22 .
Ž
.
Ž
.
w x
Ž
.
Ž
Et2O 80 mL , washed with water 3=50 mL , dried
—A solution of 20 4 2.1 g, 4.46 mmol and 19 1.7
Ž
.
.
Ž
.
MgSO4 and concentrated in vacuo. The residue was
purified by flash chromatography 5:2 light
petroleum–EtOAc to yield 19 2.5 g, 88% as a
colourless foam; TLC 5:2 light petroleum–EtOAc :
Rf 0.24; a y109.18 c 0.5, CHCl3 ; H NMR
250 MHz, CDCl3 : d 8.04–8.00 m, 2 H, Ph ,
7.58–7.39 m, 3 H, Ph , 5.75 d, 1 H, J1b,2b 5.4 Hz,
H-1b , 5.25 dd, 1 H, J3b,4b 3.1, J4b,5b -1 Hz,
g, 2.23 mmol in dry CH2Cl2 15 mL was treated at
Ž
room temperature with 0.1 M Me3SiOTf in CH2Cl2
900 mL, 90 mmol . After stirring for 30 min, the
reaction mixture was neutralized with Et3N and con-
centrated in vacuo. The residue was purified by flash
.
Ž
.
Ž
.
Ž
.
1
w x
Ž
.
D
Ž
.
Ž
.
Ž
.
chromatography 3:2 light petroleum–EtOAc to give
Ž
.
Ž
Ž
.
Ž
22 1.95 g, 81% as a colourless foam; TLC 5:4 light
.
Ž
.
w x
Ž
petroleum–EtOAc : Rf 0.31; a y75.88 c 0.5,
CHCl3 ; H NMR 250 MHz, CDCl3 : d 7.97–7.93
m, 2 H, Ph , 7.54–7.36 m, 3 H, Ph , 5.71 d, 1 H,
J1b,2b 4.9 Hz, H-1b , 5.63 d, 1 H, J1c,2c 3.1 Hz,
H-1c , 5.28–5.13 m, 4 H, H-2c,3c,4c,4b , 5.07 dd,
1 H, J1a,2a 7.7, J2a,3a 8.4 Hz, H-2a , 4.68–4.59 m, 4
H, H-6a,1a,5c,3b , 4.13–3.97 m,
D
1
.
Ž
.
Ž
.
.
H-4b , 5.19 dd, 1 H, J1b,2b 5.4, J2b,3b 11.1 Hz,
H-2b , 5.11 dd, 1 H, J2b,3b 11.1, J3b,4b 3.1 Hz,
H-3b , 5.02 dd, 1 H, J1a,2a 7.7, J2a,3a 9.2 Hz, H-2a ,
.
.
Ž
Ž
.
Ž
Ž
Ž
.
.
Ž
Ž
.
Ž
.
Ž
.
Ž
4.75 d, 1 H, J1a,2a 7.7 Hz, H-1a , 4.55–4.50 m, 2
.
Ž
X
X
.
Ž
H, H-5b,6a , 4.22 dd, 1 H, J5a,6 a 5.4, J6a,6 a 11.8
Hz, H-6 a , 3.75–3.60 m, 2 H, H-3a,5a , 2.94 d, 1
H, J3a,OH 3.6 Hz, OH , 2.87 dd, J3a,4a sJ4a,5a s10.7
Hz, 1 H, H-4a , 2.14, 2.09, 2.05 and 1.97 4 s, each 3
H, 4 Ac , 1.51–1.41 m, 1 H, CH , 1.12 d, J5b,6b 6.4
Hz, 3 H, H-6b , 0.69, 0.68, 0.67 and 0.66 4 s, each 3
H, 4 CH3 , 0.10 and 0.04 2 s, each 3 H, SiMe2 .
C35H52O14SSi 756.94 : Anal. Calcd for C, 55.24; H,
X
.
Ž
.
Ž
.
Ž
5
H, H-
X
X
.
Ž
.
Ž
6 a,2b,5b,6 b,6b , 3.79 dd, 1 H, J2a,3a 8.4, J3a,4a
.
Ž
.
Ž
.
Ž
10.7 Hz, H-3a , 3.65–3.59 m, 1 H, H-5a , 2.91 dd,
.
Ž
.
Ž
.
1 H, J3a,4a sJ4a,5a s10.7 Hz, H-4a , 2.14, 2.07, 2.05,
2.01, 1.99, 1.96, 1.73 7 s, each 3 H, 7 Ac , 1.70 s, 3
H, O3CMe , 1.49–1.39 m, 1 H, CH , 1.09 d, 3 H,
J5c,6c 6.4 Hz, 3 H-6c , 0.67, 0.66, 0.65 and 0.64 4 s,
.
Ž
Ž
.
Ž
.
Ž
.
.
Ž
.
Ž
Ž
.
.
Ž
.
Ž
6.92. Found: C, 55.31; H, 6.83.
each 3 H, 4 CH3 , 0.06 and y0.04 2 s, each 3 H,
(
.
Thexyldimethylsilyl 2, 3, 4 - tri - O - acetyl - a - L -
SiMe2 .

(
)
90
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
(
) (
)
.
Ž
.
Ž
2,3,4-Tri-O-acetyl-a-L-fucopyranosyl - 1™4 -S-
Hz, H-3a , 3.97–3.91 m, 1 H, H-5b , 3.08 dd, 1 H,
[(
(
)]
.
2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl- 1™3
J3a,4a sJ4a,5a s11.1 Hz, H-4a , 2.16, 2.15, 2.10, 2.08,
2.07, 1.96, 1.85 and 1.73 8 s, each 3 H, 8 Ac , 1.24
d, 3 H, J5c,6c 6.4 Hz, 3 H-6c .
Heptyl 2,3,4-tri-O-acetyl-a-L -fucopyranosyl -
Ž
.
-6-O-acetyl-2-O-benzoyl-4-thio-arb-D-glucopyranose
Ž
.
Ž
.
Ž
.
23 .—Compound 21 840 mg, 772 mmol was dis-
Ž
.
(
)
solved in dry tetrahydrofuran 15 mL . CH3COOH
45 mL, 795 mmol and then 1 M Bu4NF in tetrahy-
drofuran 911 mL, 911 mmol were added at 0 8C.
The mixture was slowly warmed up to room tempera-
ture and stirred for 2 h. After the addition of Et2O
50 mL , the organic layer was washed with brine
4=15 mL , dried MgSO4 , and concentrated in
vacuo. Flash chromatography 1:1 light petroleum–
EtOAc yielded 23 656 mg, 90% in the ratio a:b
Ž
.
(
)
[(
1™4 - S - 2, 3, 4, 6 - tetra - O - acetyl - b - D -
Ž
.
) ( )]
galactopyranosyl - 1™3 -6-O-acetyl-2-O-benzoyl-1,
Ž
.
4-dithio-b-D-glucopyranoside 25 .—A solution of 24
Ž
.
Ž
190 mg, 174 mmol and heptyl mercaptan 80 mL,
522 mmol in dry CH2Cl2 2.5 mL was treated at
room temperature with 0.02 M Me3SiOTf in CH2Cl2
113 mL, 2.26 mmol . After stirring for 10 min, the
reaction mixture was neutralized with Et3N and con-
centrated in vacuo. The residue was purified by flash
chromatography 7:1 toluene–acetone to yield 25
176 mg, 95% as a colourless foam; TLC 6:1
Ž
Ž
.
.
Ž
.
.
Ž
.
Ž
Ž
.
.
Ž
.
Ž
s 15:1 as a colourless foam; TLC 1:1 light
.
w x
Ž
Ž
.
petroleum–EtOAc : Rf 0.15; a y46.28 c 0.5,
D
1
.
Ž
.
.
Ž
.
Ž
CHCl3 ; H NMR 600 MHz, CDCl3 : d 8.06–8.03
Ž
.
Ž
Ž
.
w x
Ž
m, 2 H, Ph , 7.62–7.47 m, 3 H, Ph , 5.62 d, 1 H,
J1c,2c 4.3 Hz, H-1c , 5.49 dd, 1 H, J1a,OH 3.7, J1a,2a
3.6 Hz, H-1a , 5.39–5.34 m, 2 H, H-4b,4c , 5.28–
5.22 m, 2 H, H-2c,3c , 5.13–5.01 m, 3 H, H-
5c,2b,2a , 4.82 d, 1 H, J1b,2b 8.2 Hz, H-1b , 4.69
dd, 1 H, J2b,3b 10.5, J3b,4b 3.4 Hz, H-3b , 4.58 dd,
1 H, J5b,6b 3.8, J6b,6 b 13.2 Hz, H-6b , 4.52 dd, 1 H,
J5a,6a 6.4, J6a,6 a 11.2 Hz, H-6a , 4.23–4.18 m, 3 H,
H-5a,6 a,6 b , 4.14 dd, 1 H, J2a,3a 9.6, J3a,4a 10.7
Hz, H-3a , 3.93–3.90 m, 1 H, H-5b , 2.96 dd, 1 H,
J3a,4a sJ4a,5a s10.7 Hz, H-4a , 2.83 d, 1 H, J1a,OH
3.7 Hz, OH , 2.15, 2.14, 2.12, 2.08, 2.07, 1.96, 1.85
and 1.67 8 s, each 3 H, 8 Ac , 1.22 d, 3 H, J5c,6c
6.4 Hz, 3 H-6c . Anal. Calcd for C41H52O23S
944.92 : C, 52.12; H, 5.55. Found: C, 52.27; H,
toluene–acetone : Rf 0.17; a y112.28 c 0.5,
D
1
.
Ž
Ž
.
Ž
.
.
CHCl3 ; H NMR 600 MHz, CDCl3 : d 8.01–7.97
.
.
Ž
.
Ž
Ž
.
m, 2 H, Ph , 7.64–7.45 m, 3 H, Ph , 5.60 d, 1 H,
J1c,2c 4.3 Hz, H-1c , 5.34–5.31 2 H, H-4b,4c , 5.27–
5.16 m, 3 H, H-2c,3c,2a , 5.07–4.99 m, 2 H,
H-2b,5c , 4.65 m, 1 H, J1b,2b 8.1 Hz, H-1b , 4.61–
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
Ž
.
Ž
.
Ž
.
X
X
.
Ž
X
Ž
.
Ž
4.50 m, 3 H, H-6 a,6 b,3b , 4.39 d, 1 H, J1a,2a 10.1
.
Ž
X
.
Ž
.
Hz, H-1a , 4.21–4.12 m, 2 H, H-6a,6b , 3.85–3.77
X
X
.
Ž
Ž
Ž
Ž
.
Ž
.
m, 2 H, H-3a,5b , 3.63–3.57 m, 1 H, H-5a , 2.98
dd, 1 H, J3a,4a sJ4a,5a s11 Hz, H-4a , 2.64–2.56
m, 2 H, SCH2 , 2.15, 2.14, 2.09, 2.06, 2.05, 1.95,
.
Ž
.
Ž
.
.
Ž
.
.
Ž
.
Ž
1.94 and 1.85 8 s, each 3 H, 8 Ac , 1.52–1.41 m, 2
Ž
.
Ž
.
Ž
.
H, CH2 , 1.24 d, 3 H, J5c,6c 6.5 Hz, 3 H-6c ,
.
Ž
.
Ž
1.23–1.18 m, 8 H, CH2 , 0.82 dd, 3 H, J 6.4 Hz,
CH3 . Anal. Calcd for C48H66O22S2 1059.17 : C,
Ž
.
.
Ž
.
5.66.
54.43; H, 6.28. Found: C, 54.75; H, 6.20.
(
) (
)
(
) (
)
[(
2,3,4-Tri-O-acetyl-a-L-fucopyranosyl - 1™4 -S-
Heptyl a-L -Fucopyranosyl - 1™4 -S- b-D -
[(
(
)
) (
)]
2, 3, 4, 6 - tetra - O - acetyl - b - D - galactopyranosyl -
galactopyranosyl - 1™3 -1,4-dithio-b-D-glucopyra-
)]
Ž .
Ž
1™3 - 6 - O - acetyl - 2 - O - benzoyl - 4 - thio - a - D -
noside 2 .—To a solution of compound 25 60 mg,
Ž
.
.
Ž
.
glucopyranosyl trichloroacetimidate 24 .—To a so-
56 mmol in dry MeOH 8 mL was added 2 M
NaOMe in MeOH 1.6 mL . The mixture was stirred
Ž
.
Ž
Ž
.
lution of 23 600 mg, 635 mmol in dry CH2Cl2 18
.
Ž
mL were added trichloroacetonitrile 640 mL, 6.35
for 24 h at room temperature, neutralized with Am-
q
.
w
x
Ž
Ž
.
mmol and 1,8-diazabicyclo 5.4.0 undec-7-ene 2
drops . After 45 min, the mixture was concentrated in
vacuo. Flash chromatography 4:1 toluene–acetone
of the residue yielded 24 636 mg, 92% as a colour-
less foam; TLC 5:1 toluene–acetone : Rf 0.23; a
y44.28 c 0.5, CHCl3 ; H NMR 250 MHz, CDCl3 :
d 8.53 s, 1 H, NH , 7.98–7.94 m, 2 H, Ph ,
berlite IR 120 H resin, filtered, and evaporated in
vacuo. Purification of the residue by RP 18 flash
.
Ž
.
Ž
.
Ž
.
chromatography 1:1 EtOH yielded 2 33 mg, 95%
Ž
.
Ž
as a colourless powder; TLC 5:4:1 CHCl3–MeOH–
H2O : Rf 0.51; RP 18 TLC 1:1 EtOH–H2O : Rf
0.37; a D y136.78 c 0.3, MeOH ; H NMR 600
MHz, D2O : d 5.49 d, 1 H, J1c,2c 4.8 Hz, H-1c ,
4.77 d, 1 H, J1b,2b 7.4 Hz, H-1b , 4.42 dq, 1 H,
4c,5c -1, J5c,6c 6.5 Hz, H-5c , 4.35 d, 1 H, J1a,2a 10
H z , H -1 a , 3 .9 4 – 3 .3 8
H2a,3a,5a,6a,6 a,2c,3c,4c,2b,3b,4b,5b,6b,6 b , 2.72
Ž
.
w x
.
Ž
.
Ž
D
1
1
Ž
.
Ž
.
.
w x
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
Ž
.
Ž
7.64–7.43 m, 3 H, Ph , 6.54 d, 1 H, J1a,2a 3.6 Hz,
.
Ž
.
. Ž
H-1a , 5.62 d, 1 H, J1c,2c 4.2 Hz, H-1c , 5.37–5.35
Ž
J
.
Ž
.
.
Ž
m, 2 H, H-4b,4c , 5.29–5.18 m, 3 H, H-2a,2c,3c ,
m , 1 4 H ,
X
X
Ž
.
Ž
.
5.10–5.02 m, 2 H, H-2b,5c , 4.74 d, 1 H, J1b,2b 8.1
Hz, H-1b , 4.65 dd, 1 H, J2b,3b 10.4, J3b,4b 3.3 Hz,
H-3b , 4.61–4.52 m, 2 H, H-6a,6b , 4.26–4.12 m, 3
H, H-5a,6 a,6 b , 4.08 dd, 1 H, J2a,3a 9.4, J3a,4a 11.1
.
Ž
Ž
Ž
Ž
.
dd, 1 H, J3a,4a sJ4a,5a s11 Hz, H-4a , 2.62–2.53
.
Ž
.
Ž
.
Ž
.
m, 2 H, SCH2 , 1.51–1.44 m, 2 H, CH2 , 1.29–1.10
m, 8 H, CH2 , 1.05 d, J5c,6c 6.5 Hz, 3 H, 3 H-6c ,
X
X
.
Ž
.
Ž
.

(
)
T. Eisele et al.rCarbohydrate Research 306 1998 81–91
91
w
x Ž .
10 a R. Bommer, W. Kinzy, and R.R. Schmidt, Liebigs
Ž
.
0.69 dd, 3 H, J 6.6 Hz, CH3 . Anal. Calcd for
Ž
.
Ž .
Ann. Chem., 1991 425–433; b R. Bommer, Dis-
Ž
.
C25H46O13S2 P0.75H2O 632.27 : C, 47.49; H, 7.57.
Found: C, 47.48; H, 7.70.
Ž .
sertation, Univ. Konstanz, 1990; c H. Kunz and C.
Ž
.
Ž
Unverzagt, Angew. Chem., 100 1988 1763–1765;
Ž .
.
d
Angew. Chem. Int. Ed. Engl., 27 1988 1697–
1699.
x Ž .
Acknowledgements
w
w
11 a R. Windmuller and R.R. Schmidt, Tetrahedron
¨
Ž
.
Ž .
b R. Windmuller,
Lett., 35 1994 7927–7930;
Diplomarbeit, Univ. Konstanz, 1990.
x Ž .
¨
Acknowledgement This work was supported by
the Deutsche Forschungsgemeinschaft, the Fonds der
Chemischen Industrie, and Hoechst AG, Frankfurt.
12
a
R. Gigg and C.D. Warren, J. Chem. Soc. C,
Ž .
Ž
.
1968 1903–1911; b P.A. Gent and R. Gigg, J.
Chem. Soc., Chem. Commun., 1974 277–278.
Ž
.
w
w
x Ž .
Ž
.
13 a M. Mikamo, Carbohydr. Res., 191 1989 150–
Ž .
14 a S. David, A. Thieffry, and A. Veyrieres, J. Chem.
153; b J. Peter, Diplomarbeit, Univ. Konstanz, 1994.
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x Ž .
Ž
.
Ž .
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w x
Ž
.
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7 T. Eisele and R.R. Schmidt, Liebigs Ann., submitted.
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.
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1992 644–651; c O. Dangles, F. Guibe, and G.
´
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Ž
.
8 T. Eisele, Dissertation, Univ. Konstanz, 1996.
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.
18 G. Zemplen, Ber. Dtsch. Chem. Ges., 60 1927
´
Ž
.
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