From glycoside hydrolases to thioglycoligases: The synthesis of thioglycosides

Article abstract of DOI:10.1016/j.tetasy.2004.12.004

The treatment of various glycosyl acceptors, each containing a reactive thiol group, with the appropriate glycosyl donor and a glycoside hydrolase or glycosynthase, failed to yield any thioglycosides - only the products of O-glycosylation were formed. However, thioglycosides were formed when a thioglycoligase was used to mediate the reaction between acceptor and donor. In fact, pyranose acceptors possessing a thiol group at C3, C4 or C6 (but not C2) were all capable of conversion into thioglycosides. Some comment is given regarding the mechanism of the various processes.

Full text of DOI:10.1016/j.tetasy.2004.12.004

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 321–335
From glycoside hydrolases to thioglycoligases: the synthesis
of thioglycosides
Robert V. Stick* and Keith A. Stubbs
Chemistry, School of Biomedical and Chemical Sciences M313, University of Western Australia, Crawley, WA 6009, Australia
Received 22 September 2004; accepted 2 December 2004
This paper is dedicated to the memory of Jacques van Boom
Abstract—The treatment of various glycosyl acceptors, each containing a reactive thiol group, with the appropriate glycosyl donor
and a glycoside hydrolase or glycosynthase, failed to yield any thioglycosides––only the products of O-glycosylation were formed.
However, thioglycosides were formed when a thioglycoligase was used to mediate the reaction between acceptor and donor. In fact,
pyranose acceptors possessing a thiol group at C3, C4 or C6 (but not C2) were all capable of conversion into thioglycosides. Some
comment is given regarding the mechanism of the various processes.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis of such disaccharides has generally involved
either the alkylation of a 1-thio sugar with a sugar tri-
flate6 or the glycosylation of a 4-thio sugar with a glyco-
syl bromide (Scheme 1).7 Indeed, in our hands,
treatment of the hemithioacetal 4 with the triflate 5 gave
the thioglycoside 6, a direct precursor of the sulfur-
linked disaccharide derivative 7 (Scheme 2). We required
such ÔdoubleÕ thioglycosides to act as stable glycosyl
acceptors in some other trans-glycosylation experiments
(not described here) with wild-type enzymes.
The replacement of one of the oxygen atoms at the ano-
meric carbon of a glycoside by a sulfur atom leads to
two distinctly different thio sugars, namely a 5-thio gly-
coside 1 and a 1-thio glycoside 2 (Fig. 1). Molecules with
the structural elements of 1 are rarely found as natural
products but synthetic molecules are not uncommon.1,2
In stark contrast, molecules based on 2 are not uncom-
mon natural products3 and constitute one of the most
frequently synthesised glycosyl donors for the construc-
tion of the glycosidic linkage.4
It occurred to us, as it must have to countless others,
that an enzyme-assisted approach should be able to con-
struct the thioglycosidic linkage. In fact, there are very
few reports of a glycoside hydrolase being used to cause
a reactive glycosyl donor to glycosylate a simple thiol
acceptor, let alone the thiol group of a thio sugar.8–10
We became interested in thioglycosides with the revela-
tion by Driguez et al. of the ability of sulfur-linked
disaccharides, such as 3, to act as potent, nonhydrolys-
able inhibitors of b-glucosidases and cellulases.5 The
OH
OH
OH
OH
OH
S
O
O
HO
HO
HO
HO
HO
HO
HO
OR
SR
S
O
OH
OH
OH
OH
1
2
3
Figure 1.
*
Corresponding author. E-mail: rvs@chem.uwa.edu.au
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.12.004

322
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
OP
OP
O
O
PO
PO
PO
PO
SH
PO
PO
OR
Br
OP
PO
+
O
+
PO
PO
PO
S
O
TfO
PO
OP
OP
OP
O
O
HS
PO
PO
PO
PO
P = protecting group
OR
OR
Scheme 1.
TfO
OMe
OBz
OAc
OAc
BzO
O
O
O
a
AcO
AcO
BzO
S
AcO
AcO
+
BzO
SH
O
BzO
AcO
AcO
OBz
OMe
4
5
6
OAc
AcO
b
O
AcO
AcO
SPh
AcO
S
O
AcO
OAc
7
Scheme 2. Reagents and conditions: (a) DBU, PhMe; (b) (i) Na, MeOH; (ii) Ac2O, pyr.; (iii) 18 M H2SO4, Ac2O; (iv) 30% HBr, AcOH; (v) PhSH,
Et3N, CH2Cl2.
HO
HO
OH
OH
OAc
O
O
O
a
b
AcS
AcO
SPh
SPh
AcO
SPh
HO
AcO
HO
AcO
9
8
Scheme 3. Reagents and conditions: (a) (i) PhCH(OEt)2, CSA, CHCl3; (ii) Ac2O, pyr.; (iii) AcOH/H2O (4:1); (b) (i) AcCl, pyr., CH2Cl2; (ii) Tf2O,
pyr., CH2Cl2; (iii) KSAc, THF.
2. Results and discussion
glucopyranosyl fluoride 12, first with sodium methoxide
in methanol, then with the glycosynthase, Abg E358S;11
also formed was an amount of the trisaccharide 13, the
product expected from the further glycosylation of the
intermediate disaccharide (Scheme 5).
In order to explore such a process more fully, we pre-
pared the 1,4-dithio-D-glucoside 9 (Scheme 3) and then
mixed it with 4-nitrophenyl tetra-O-acetyl-b-D-gluco-
pyranoside 10 in the presence of sodium methoxide in
methanol. A subsequent treatment of the presumed thiol
and donor with Abg (a retaining exo-b-glucosidase from
Agrobacterium sp.; Scheme 4) gave none of the expected
thioglycoside; eventually isolated was the 1,3-b-linked
disaccharide 11. The same result was obtained when
the D-glucoside 9 was treated with tetra-O-acetyl-a-D-
Out of interest we also subjected the D-glucoside 9 and
tetra-O-acetyl-a-D-galactopyranosyl fluoride 14 to the
normal deacetylation protocol, and then Abg E358S––
a 1,3-b-linked disaccharide 15 was again formed, and
at a higher rate than the comparable glycosylation with
the fluoride 12 (Scheme 6). We even tried to vary the pH
OAc
O
OAc
OAc
a
O
O
AcS
O
AcO
AcO
AcO
+
9
SPh
AcO
OC6H4NO2-4
AcO
10
AcO
AcO
11
Scheme 4. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg wild-type, phosphate buffer, pH 7.0; (iii) Ac2O, pyr.
OAc
OAc
OAc
a
AcO
O
O
+
11
O
AcO
AcO
+
9
AcS
O
AcO
AcO
O
AcO
SPh
O
OAc
AcO
AcO
AcO
F
12
13
Scheme 5. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg E358S, 150 mM NH4HCO3; (iii) Ac2O, pyr.

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
323
OAc
OAc
AcO
AcO
OAc
OAc
AcO
AcO
OAc
O
O
O
O
AcS
a
AcS
O
SPh
AcO
SPh
+
9
O
SPh
AcO
19
AcO
20
AcO
AcO
AcO
F
15
14
Figure 2.
Scheme 6. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg E358S,
150 mM NH4HCO3 or 100 mM citrate buffer, pH 5.5; (iii) Ac2O, pyr.
HO
OBz
OBz
O
O
a
(5.5–8.4) of the media for the glycosynthase-mediated
reactions described so far, in the hope of changing the
ionisation state of the thiol group in the acceptor, but
to no avail––the 1,3-b-linked product was always
formed.
BzO
BzO
BzO
b
BzO
OMe
OMe
There was a concern that the thiol acceptor had been
somehow converted during the various reactions into
the disulfide 16 (Scheme 7). We therefore prepared 16
by the oxidation of the thiol with iodine, and subjected
the product to a glycosynthase-mediated reaction with
14. After no initial reaction, the addition of 1,4-dithio-
erythritol (DTE) caused the formation again of the
1,3-b-linked disaccharide 15. Also of a confirmatory
nature was the glycosylation, under glycosynthase con-
trol, of the thioglycoside 17 by the donor derived from
14, giving the 1,4-b-linked disaccharide 18 (Scheme 8).
HO
OAc
O
a
20
SPh
AcO
AcO
Scheme 9. Reagents and conditions: (a) (i) PhOC(S)Cl, pyr., CH2Cl2;
(ii) Bu3SnH, AIBN, PhMe; (b) (i) Na, MeOH; (ii) Ac2O, pyr.;
(iii) 18 M H2SO4, Ac2O; (iv) PhSH, Et2OBF3, CH2Cl2.
mixture, that the initial glycosylation is a slow process,
followed by the more rapid glycosylation of the interme-
diate disaccharide to form the observed mixture of
products. We also investigated the treatment of 20 with
tetra-O-acetyl-a-D-galactopyranosyl fluoride 14 in the
presence of the glycosynthase Abg E358S––the
expected disaccharide 24 was formed in good yield
(Scheme 11).
OAc
O
S
AcO
a
b
9
SPh
15
AcO
16
2
Having established that the triol derived from the deoxy
sugar 20 was a viable, if slow, acceptor for glycosynth-
ase-mediated reactions, we continued towards our syn-
thesis of 19 (Fig. 2; Scheme 12). Although the
thioglycoside 8 could be easily converted into the alco-
hol 25 and the 3-deoxy alcohol 26, the subsequent
attempt to introduce sulfur at C4 of the unstable triflate
27 yielded only the alkene 28; the mesylate derived from
26 fared no better. A Mitsunobu reaction on 26 with
thioacetic acid again produced only the alkene 28. This
result was in direct contrast to the successful Mitsunobu
reaction on 26 with chloroacetic acid, followed by selec-
tive hydrolysis of the product 29 and another successful
Mitsunobu reaction on the alcohol 30, this time with
thioacetic acid (Scheme 13).
Scheme 7. Reagents and conditions: (a) (i) Na, MeOH; (ii) I2, Et3N,
CHCl3; (iii) Ac2O, pyr.; (b) (i) 14, Na, MeOH; (ii) Abg E358S, 150 mM
NH4HCO3, 1,4-DTE; (iii) Ac2O, pyr.
In light of the inability of a hydrolase or glycosynthase
to cause the glycosylation of the thiol derived from 9,
at sulfur, we decided to check the potential of the 3-
deoxy-1,4-dithio sugar 19 (Fig. 2)––surely the absence
of the hydroxyl group at C3 would force the molecule
to undergo glycosylation at sulfur (at C4) of the derived
thiol. A useful preliminary check to see if a thiol was
having any other effect on the process would be to
attempt the glycosylation of the triol derived from the
4-deoxy sugar 20 (Scheme 9).
Treatment of the 4-deoxy sugar 20 with tetra-O-acetyl-
a-D-glucopyranosyl fluoride 12 according to the normal
deacetylation/glycosynthase protocol gave, in a very
slow process, a mixture of the tri- and tetrasaccharides
21 and 22 (Scheme 10). It is obvious, from the absence
of any disaccharide product 23 (Fig. 3) in the final
Although the synthesis of 19 had eluded us, we were
heartened by the appearance of a paper by Withers
and co-workers that announced the use of an acid–base
mutant of a glycoside hydrolase (E171A from the same
retaining b-glucosidase from Agrobacterium sp.) for the
OH
OAc
AcO
O
O
a
AcO
AcO
O
HO
HO
14 +
SPh
AcO
SPh
O
HO
17
AcO
OAc
18
Scheme 8. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg E358S, 150 mM NH4HCO3; (iii) Ac2O, pyr.

324
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
OAc
AcO
OAc
OAc
a
O
O
O
AcO
AcO
+
20
O
AcO
AcO
AcO
SPh
O
O
AcO
AcO
AcO
OAc
F
21
12
+
OAc
OAc
OAc
AcO
O
O
O
O
AcO
AcO
AcO
AcO
O
SPh
O
O
OAc
AcO
AcO
AcO
22
Scheme 10. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg E358S, 150 mM NH4HCO3; (iii) Ac2O, pyr.
OAc
OAc
AcS
OBz
OBz
O
O
AcO
AcO
a
O
O
XO
26
O
SPh
SPh
SPh
AcO
AcO
BzO
BzO
c
23
29 X = ClCH2CO
30 X = H
b
Figure 3.
Scheme 13. Reagents and conditions: (a) ClCH2CO2H, Ph3P, DEAD,
CH2Cl2; (b) NH2CSNH2, 2,6-lutidine, MeOH/CH2Cl2 (1:1); (c)
CH3C(O)SH, Ph3P, DEAD, CH2Cl2.
AcO
AcO
OAc
AcO
AcO
OAc
OAc
a
O
O
O
+
20
SPh
O
AcO
AcO
AcO
F
24
14
1,3-b-linked disaccharide 34 was virtually the sole prod-
uct (Scheme 17). A similar result was obtained on the
4-nitrophenyl b-D-glucoside 35, to produce the disacchar-
ide 36. Also readily available was the thioacetate 37
(Scheme 18), the derived thiol shown to be a reasonable
acceptor in the thioglycoligase-mediated reaction with
the donor 31 (Scheme 19). We reached the limit of the
process with the thiol derived from the thioacetate 38
(Scheme 20)––there was no evidence for a successful gly-
cosylation at sulfur in the presence of 31 and the
thioglycoligase.
Scheme 11. Reagents and conditions: (a) (i) Na, MeOH; (ii) Abg
E358S, 150 mM NH4HCO3; (iii) Ac2O, pyr.
synthesis of thioglycosides.12 These ÔthioglycoligasesÕ
were capable of transferring a reactive donor, such as
31, via a glycosyl–enzyme intermediate 32, onto the thiol
group of a suitable acceptor (Scheme 14).
With this new methodology at hand, we treated the thiol
derived from 9 with the donor 31 in the presence of the
thioglycoligase––the 1,4-b-linked disaccharide 7 was
formed in good yield (Scheme 15). Would such a liga-
tion be possible on a thiol located at another position
of the pyranose ring, a proposal investigated somewhat
by Jahn and Withers?13 We therefore prepared the thio-
acetate 33 (Scheme 16) and treated the derived thiol with
the donor 31 in the presence of the thioglycoligase––the
Our final foray into thioglycoside formation drew on
some related results with glycosynthases––the glycosyl-
ation of 6-O-benzyl-D-glucopyranose 39 with a-D-galacto-
pyranosyl fluoride in the presence of Abg E358S had
given, somewhat surprisingly, a mixture of 1,2-b- and
1,3-b-linked disaccharides 41 and 42 (Scheme 21).14
Would, then, the thiol derived from a thioacetate such
HO
AcO
HO
HO
OH
OBz
OBz
O
O
O
a
b
HO
SPh
TfO
SPh
SPh
HO
BzO
BzO
25
8
26
OBz
OBz
e
O
c
O
d
SPh
SPh
BzO
27
BzO
28
Scheme 12. Reagents and conditions: (a) (i) 2,2-dimethoxypropane, CSA; (ii) BzCl, pyr., CH2Cl2; (iii) AcOH/H2O (4:1); (iv) CH3C(OEt)3,
CF3COOH, CHCl3; (v) MeCN, H2O; (b) (i) PhOC(S)Cl, pyr., CH2Cl2; (ii) Bu3SnH, AIBN, PhMe; (iii) HCl, MeOH; (c) Tf2O, pyr., CH2Cl2; (d)
KSAc, DMF; (e) CH3C(O)SH, Ph3P, DEAD, CH2Cl2.

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
325
OH
OH
OH
O
HS
HO
E171A
O
O
HO
HO
OR
HO
HO
HO
OC6H3(NO2)2-2,4
80 mM phosphate buffer
pH 7.4
HO
HO
O
O
31
32
OH
HO
O
HO
HO
HO
OR
S
O
HO
OH
Scheme 14.
OAc
OAc
AcO
O
O
a
AcO
AcO
AcO
S
SPh
AcS
AcO
+
31
SPh
O
AcO
AcO
OAc
7
9
Scheme 15. Reagents and conditions: (a) (i) Na, MeOH; (ii) E171A, 80 mM phosphate buffer, pH 7.4; (iii) Ac2O, pyr.
O
O
O
O
O
O
SAc
O
OH
O
O
a
c
b
O
O
O
O
O
OH
O
OAc
OAc
d
O
O
33 X = SPh
35 X = OC6H4NO2-4
AcO
AcS
AcO
AcS
X
OAc
AcO
AcO
Scheme 16. Reagents and conditions: (a) (i) PDC, Ac2O, CH2Cl2; (ii) NaBH4, EtOH/H2O (3:7); (b) (i) Tf2O, pyr., CH2Cl2; (ii) KSAc, DMF; (c) (i)
CF3COOH/H2O (4:1); (ii) NaOAc, Ac2O; (d) (i) PhSH or 4-nitrophenol, Et2OBF3, CH2Cl2.
OAc
OAc
OAc
34 X = SPh
O
O
O
a
AcO
AcO
AcO
AcO
AcO
31
a
S
36 X = OC6H4NO2-4
S
X
+
31
37
AcO
AcO
AcO
AcO
O
AcO
SPh
Scheme 17. Reagents and conditions: (a) (i) Na, MeOH; (ii) 33 or 35,
E171A, 80 mM phosphate buffer, pH 7.4; (iii) Ac2O, pyr.
AcO
Scheme 19. Reagents and conditions: (a) (i) Na, MeOH; (ii) E171A,
80 mM phosphate buffer, pH 7.4; (iii) Ac2O, pyr.
as 43 (Fig. 4) shows the same pattern of glycosylation
under the control of the thioglycoligase?
then gave the triacetate 47, which, to our surprise, gave
only the tetraacetate 48 upon standard acetolysis. More
successful was a parallel sequence on methyl a-D-
mannopyranoside that used 4-nitrobenzyl bromide as
the alkylating agent and proceeded through the interme-
diates 49–52––an acetolysis on 52, with a less basic resi-
due at C6, smoothly gave the tetraacetate 53.
Our approach to the synthesis of 43 is outlined in
Scheme 22. Methyl a-D-mannopyranoside was easily
converted into the alcohol 44 (characterised as its acetate
45) that allowed for the introduction of a sulfur atom at
C2 (the thioacetate 46). Protecting group manipulations
OH
OH
SAc
O
a
b
O
O
HO
HO
AcO
AcO
AcO
AcO
SPh
SPh
SPh
HO
AcO
AcO
37
17
Scheme 18. Reagents and conditions: (a) (i) TrCl, Et3N, DMAP, DMF; (ii) Ac2O, pyr.; (iii) AcOH/H2O (4:1); (b) (i) MsCl, Et3N, CH2Cl2; (ii) KSAc,
DMF.

326
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
OAc
HO
OAc
OAc
O
O
b
AcO
AcO
a
O
AcO
AcO
AcO
AcO
SPh
OAc
OAc
AcS
38
AcS
Scheme 20. Reagents and conditions: (a) (i) Tf2O, pyr., CH2Cl2; (ii) KSAc, DMF; (b) (i) PhSH, Et2OBF3, CH2Cl2.
OBn
O
HO
OH
OBn
AcO
AcO
O
O
OAc
a
HO
HO
+
O
HO
O
OAc
HO
HO
OH
F
AcO
OAc
41
39
AcO
+
OBn
AcO
AcO
OAc
O
O
AcO
O
OAc
AcO
AcO
42
Scheme 21. Reagents and conditions: (a) (i) Abg E358S, 150 mM NH4HCO3; (ii) Ac2O, NaOAc.
OBn
It is interesting to reflect on some of the chemistry
underlying the various transformations reported in this
paper. First, the measured pKa (8.5) of phenyl 1,4-
dithio-b-D-glucopyranoside (the thiol derived from the
deacetylation of 9) is commensurate with a molecule
containing a slightly more acidic (than normal) thiol resi-
due. Second, in light of this information and the fact
that the thiol does not act as an acceptor in either glyco-
side hydrolase or glycosynthase-mediated process, the
thiol must not be able to bind in its neutral form in
the active site of either enzyme––the amino acid residues
in this site must be capable of causing ionisation of the
O
AcO
AcO
SAc OAc
43
Figure 4.
Unfortunately, treatment of the thioacetate 53, under
the normal deacetylation conditions, with the donor 31
in the presence of the thioglycoligase gave no evidence
for the formation of a disaccharide.
OR
OMe
OAc
O
O
O
OMe
OMe
b
45 R = Bn
50 R = CH2C6H4NO2-4
OR
OH
OR
OH
OMe
OMe
OH
O
O
O
c
a
O
O
HO
HO
O
O
AcS
OMe
OMe
OMe
OMe
46 R = Bn
OMe
44 R = Bn
51 R = CH2C6H4NO2-4
49 R = CH2C6H4NO2-4
OCH2C6H4NO2-4
O
OR
O
AcO
AcO
AcO
AcO
d
AcS
OAc
AcS
OMe
47 R = Bn
48 R = Ac
53
e
e
52 R = CH2C6H4NO2-4
Scheme 22. Reagents and conditions: (a) (i) 2,3-butanedione, HC(OMe)3, MeOH, CSA; (ii) (Bu3Sn)2O, PhMe; (ii) BnBr or 4-NO2C6H4CH2Br; (b)
Ac2O, pyr.; (c) (i) Tf2O, pyr., CH2Cl2; (ii) KSAc, DMF; (d) (i) CF3COOH/H2O (19:1); (ii) Ac2O, pyr.; (e) 18 M H2SO4, Ac2O.

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
327
CO2
CO2
CO2
CH3
CO2
OH
OH
OH
O
O
O
S
HO
S
HO
S
HO
SPh
SPh
SPh
HO
HO
HO
CH2OH
A (glycoside hydrolase)
B (glycosynthase)
C (thioglycoligase)
Scheme 23.
thiol, so generating a thiolate ion that is repulsed by the
general acid/base (carboxylate) of the enzyme (Scheme
23 A and B). Only when this residue is mutated to a be-
nign methyl group (of alanine) is the thiolate able to
bind in the active site of the enzyme (thioglycoligase)
(Scheme 23C). Similar comments have been made by
Jahn and Withers in their most recent publication on
thioglycoligases.13
170.24, 170.25 (7 · C, C@O). HR-MS (FAB) m/z
745.1825 [C32H41O16S2 (M+H)+ requires 745.1836].
(b) NaOMe (10%) in MeOH (5 mL) was added to thio-
acetate 9 (50 mg, 0.11 mmol) in MeOH (5 mL) and the
solution stirred (rt, 10 min). The mixture was quenched
with resin (Amberlite IR-120, H+), filtered and concen-
trated. The residue was taken up in 80 mM phosphate
buffer (pH 6.8, 5 mL) and the D-glucoside 31 (76 mg,
0.22 mmol) and Abg E171A (2 mg) added and the solu-
tion kept at 25 ꢁC for 24 h. The solution was concen-
trated and the residue dissolved in pyridine (5 mL),
then Ac2O (5 mL) was added and the solution stirred
(rt, 12 h). The mixture was quenched by the addition
of MeOH (5 mL) and concentrated. Standard work-up
(CH2Cl2) and flash chromatography (EtOAc/petrol
1:4–1:1) gave disaccharide 7 as a colourless oil (68 mg,
It goes almost without saying that, with thioglycolig-
ases, which lack the general acid/base residue, O-alkyl-
ation, and hence oligomerisation of the initially
formed disaccharide, is not possible.
3. Experimental
1
General experimental procedures have been given
previously.15
84%). The H and 13C NMR spectra were consistent
with those reported in (a).
3.1. Synthesis of the disaccharide 7
3.2. Synthesis of the 1,4-dithio-D-glucoside 9
(a) (i) Tetra-O-acetyl-b-D-glucopyranosyl-(1!4)-tri-O-
acetyl-4-thio-b-D-glucosyl bromide: HBr (30%) in AcOH
(3 mL) was added to tetra-O-acetyl-b-D-glucopyranosyl-
(1!4)-tetra-O-acetyl-4-thio-D-glucose16 (200 mg) in
CH2Cl2 (5 mL) and the solution stirred (rt, 30 min).
Standard workup (CH2Cl2) gave a colourless oil
(200 mg), presumably the title bromide, which was used
without purification.
(i) Phenyl 2,3,6-tri-O-acetyl-1-thio-b-D-galactopyrano-
side: Acetyl chloride (0.27 mL, 1.6 mmol) in CH2Cl2
(5 mL) was added dropwise to phenyl 2,3-di-O-acetyl-
1-thio-b-D-galactopyranoside17 (500 mg, 1.4 mmol) and
pyridine (0.20 mL, 2.2 mmol) in CH2Cl2 (15 mL) at
ꢀ30 ꢁC and the solution stirred (30 min). Methanol
(10 mL) was added, followed by a standard work-up
(CH2Cl2). Flash chromatography (EtOAc/petrol 1:4)
then gave the title triacetate as colourless plates
(520 mg, 80%), mp 126–129 ꢁC (EtOH), [a]D = +26.2 (c
1, CHCl3). Found: C, 54.2; H, 5.6. C18H22O8S requires
C, 54.3; H, 5.6. 1H NMR (300 MHz): d 2.05, 2.08,
2.09 (3 · s, 9H, CH3), 3.80 (ddd, J4,5 1.0, J5,6 5.5, 5.8,
H5), 4.08 (dd, J3,4 3.2, H4), 4.27–4.35 (m, H6,6), 4.70
(d, J1,2 10.1, H1), 4.97 (dd, J2,3 9.8, H3), 5.27 (dd,
H2), 7.28–7.31, 7.49–7.53 (2 · m, Ph). 13C NMR
(75.5 MHz): d 20.71, 20.73, 20.76 (3 · C, CH3), 62.69
(C6), 67.14, 67.43, 74.18 (C2,3,4), 75.86 (C5), 86.27
(C1), 127.90, 128.81, 132.21, 132.58 (Ph), 166.57,
170.13, 170.82 (3 · C, C@O). HR-MS (FAB) m/z
399.2066 [C18H23O8S (M+H)+ requires 399.2052].
(ii) Phenyl tetra-O-acetyl-b-D-glucopyranosyl-(1!4)-tri-
O-acetyl-1,4-dithio-b-D-glucoside 7: Thiophenol (64 mg,
0.60 mmol) and K2CO3 (81 mg, 0.60 mmol) were added
to the above bromide (200 mg) in acetone (5 mL) and
the resulting mixture stirred (rt, 30 min). Concentration
of the mixture, followed by flash chromatography
(EtOAc/petrol 3:7), gave the thioglycoside 7 as a colour-
1
less oil (170 mg, 81%), [a]D = ꢀ42.6 (c 1, CHCl3). H
NMR (500 MHz): d 1.82, 1.95, 1.98, 1.99, 2.01, 2.05,
2.08 (7 · s, 21H, CH3), 2.91 (dd, J3,4 ꢁ J4,5 11.0, H4),
3.69 (ddd, J4 ;5 9.8, J5 ;6 2.3, 6.4, H50), 3.83 (ddd, J5,6
0
0
0
0
1.9, 5.3, H5), 4.03 (dd, J6 ;6 12.3, H60), 4.12 (dd, H60),
4.34 (dd, J6,6 12.1, H6), 4.61 (dd, H6), 4.63 (d, J1,2
0
0
10.1, H1), 4.71 (d, J1 ;2 10.0, H10), 4.88 (dd, J2,3 9.1,
(ii) Phenyl 2,3,6-tri-O-acetyl-1-thio-4-O-trifluorometh-
anesulfonyl-b-D-galactoside: Trifluoromethanesulfonic
anhydride (0.13 mL, 0.75 mmol) was added to the above
triacetate (310 mg, 0.69 mmol) in CH2Cl2 (10 mL) and
pyridine (200 lL, 2.0 mmol) at ꢀ30 ꢁC and the solution
stirred (30 min). Saturated NaHCO3 solution (5 mL)
was added and a standard work-up (CH2Cl2) gave a col-
ourless oil (350 mg), presumably the title triflate, which
was used without purification.
0
0
H2), 4.91 (dd, J2 ;3 9.3, H20), 4.94 (dd, J3 ;4 9.3, H40),
5.14 (dd, H3), 5.17 (dd, H30), 7.25–7.29, 7.46–7.49
(2 · m, Ph). 13C NMR (125.7 MHz): d 20.25, 20.36,
20.42, 20.44, 20.45, 20.69, 20.72 (7 · C, CH3), 46.21
(C4), 62.37 (C60), 63.59 (C6), 68.23 (C40), 70.05 (C20),
71.11 (C3), 71.35 (C2), 73.55 (C30), 75.63 (C50), 77.88
(C5), 81.46 (C10), 85.86 (C1), 128.50, 128.85, 131.55,
133.67 (Ph), 169.12, 169.31, 169.33, 169.87, 169.92,
0
0
0
0

328
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
(iii) Phenyl 2,3,6-tri-O-acetyl-4-S-acetyl-1,4-dithio-b-D-
glucoside 9: Potassium thioacetate (190 mg, 1.7 mmol)
was added to the above triflate (350 mg) in dry THF
(10 mL) and the mixture stirred (rt, 16 h). Filtration
and concentration of the mixture, followed by a stan-
dard work-up (CH2Cl2) and flash chromatography
(EtOAc/petrol 1:4), gave the thioacetate 9 as a colourless
oil (250 mg, 88%), [a]D = ꢀ23.5 (c 1, CHCl3). Found: C,
trated. The residue was dissolved in NH4HCO3 solution
(2 mL of 150 mM), and Abg E358S (2 mg) was added
and the solution kept at 25 ꢁC for 2 h). The solution
was concentrated and the residue dissolved in pyridine
(5 mL), then Ac2O (5 mL) was added and the solution
stirred (rt, 12 h). The mixture was quenched by the addi-
tion of MeOH (5 mL), concentrated and subjected to a
standard work-up (CH2Cl2). Flash chromatography
(EtOAc/petrol 1:4–1:1) gave disaccharide 11 as a colour-
1
52.6; H, 5.6. C20H24O8S2 requires C, 52.5; H, 5.5. H
1
NMR (300 MHz): d 2.00, 2.09 (2 · s, 9H, CH3CO),
2.32 (s, CH3COS), 3.65 (dd, J3,4 11.2, J4,5 11.1, H4),
3.85 (ddd, J5,6 2.3, 5.9, H5), 4.29–4.34 (m, H6,6), 4.73
(d, J1,2 10.1, H1), 4.95 (dd, J2,3 8.9, H2), 5.24 (dd,
H3), 7.31–7.34, 7.47–7.50 (2 · m, Ph). 13C NMR
(125.7 MHz): d 20.52, 20.73, 20.75 (3 · C, CH3CO),
30.71 (CH3COS), 44.00 (C4), 63.35 (C6), 71.12, 72.18,
76.68 (C2,3,5), 85.71 (C1), 128.22, 128.88, 131.99,
132.84 (Ph), 166.37, 170.01, 170.61 (3 · C, C@O),
192.63 (SC@O). HR-MS (FAB) m/z 457.0973
[C20H25O8S2 (M+H)+ requires 457.0990].
less oil (28 mg, 26%). The H and 13C NMR spectra
were consistent with those reported in (a).
Next to elute was phenyl tetra-O-acetyl-b-D-glucopyr-
anosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucosyl-(1!3)-2,6-
di-O-acetyl-4-S-acetyl-1,4-dithio-b-D-glucoside 13, ob-
tained as colourless needles (47 mg, 52%), mp 100–
103 ꢁC (EtOH), [a]D = ꢀ44.8 (c 1, CHCl3). Found: C,
1
51.5; H, 5.4. C44H56O24S2 requires C, 51.2; H, 5.5. H
NMR (500 MHz): d 1.97, 1.99, 2.00, 2.02, 2.06, 2.07,
2.14, 2.18 (8 · s, 27H, CH3CO), 2.25 (s, CH3COS),
0
0
3.21 (dd, J3,4 10.3, J4,5 10.5, H4), 3.54 (ddd, J4 ;5 10.3,
J5 ;6 1.9, 5.5, H50), 3.63 (ddd, J4 ;5 10.4, J5 ;6 2.3, 4.4,
0
0
00 00
00 00
3.3. Phenyl tetra-O-acetyl-b-D-glucopyranosyl-(1!3)-
2,6-di-O-acetyl-4-S-acetyl-1,4-dithio-b-D-glucoside 11
H500), 3.75 (dd, J3 ;4 9.4, H40), 4.01 (dd, J6 ;6 12.5,
0
0
00 00
H600), 4.05 (m, J6 ;6 11.5, H5,60), 4.23 (m, J2,3 9.8, J5,6
0
0
(a) NaOMe (10%) in MeOH (2 mL) was added to 4-
nitrophenyl b-D-glucoside 1018 (80 mg, 0.17 mmol) and
the thioacetate 9 (75 mg, 0.14 mmol) in MeOH (3 mL)
and the solution stirred (rt, 30 min). The mixture was
quenched with resin (Amberlite IR-120, H+), filtered
and concentrated. The residue was dissolved in a phos-
phate buffer (pH 7, 2 mL), and Abg (2 mg) added and
the solution kept at 25 ꢁC for 2 h. The solution was con-
centrated and the residue dissolved in pyridine (5 mL),
then Ac2O (5 mL) was added and the solution stirred
(rt, 12 h). The mixture was quenched by the addition
of MeOH (5 mL), concentrated and subjected to a stan-
dard work-up (CH2Cl2). Flash chromatography
(EtOAc/petrol 1:4–1:1) gave the disaccharide 11 as a col-
ourless oil (20 mg, 18%), [a]D = ꢀ34.1 (c 1, CHCl3).
Found: C, 51.9; H, 5.2. C32H40O16S2 requires C, 51.6;
5.5, J6,6 12.8, H3,6), 4.33 (dd, H600), 4.37 (dd, J5,6 3.7,
H6), 4.44 (dd, H60), 4.47 (d, J1 ;2 7.9, H100), 4.64 (d,
00 00
J1 ;2 8.1, H10), 4.66 (d, J1,2 10.1, H1), 4.87 (dd, J2 ;3
0
0
0
0
7.8, H20), 4.91 (dd, J2 ;3 8.0, H200), 4.97 (dd, H2), 5.04
00 00
(dd, J3 ;4 9.7, H400), 5.07 (dd, H30), 5.12 (dd, H300),
7.25–7.30, 7.43–7.47 (2 · m, Ph). 13C NMR
(125.7 MHz): d 20.35, 20.40, 20.43, 20.56, 20.73, 20.80,
21.07 (CH3CO), 30.53 (CH3COS), 45.51 (C4), 61.51
(C600), 61.93 (C60), 63.91 (C6), 67.74 (C40), 70.96 (C20),
71.53 (C200), 71.97 (C500), 72.75, 72.76, 72.78 (C30,50,
300), 73.39 (C2), 75.65 (C5), 76.33 (C400), 76.51 (C3),
86.38 (C1), 100.38 (C10), 100.80 (C100), 127.80, 127.83,
131.95, 133.24 (Ph), 168.98, 169.17, 169.21, 169.58,
169.79, 170.11, 170.18, 170.32, 170.57 (9 · C, C@O),
194.43 (SC@O). HR-MS (FAB) m/z 1033.2633
[C44H57O24S2 (M+H)+ requires 1033.2681].
0
00
1
H, 5.4. H NMR (500 MHz): d 1.98, 2.01, 2.04, 2.08,
2.10, 2.20 (6 · s, 18H, CH3CO), 2.26 (s, CH3COS),
3.4. Phenyl tetra-O-acetyl-b-D-galactopyranosyl-(1!3)-
2,6-di-O-acetyl-4-S-acetyl-1,4-dithio-b-D-glucoside 15
0
0
0
0
3.18 (dd, J3,4 ꢁ J4,5 10.7, H4), 3.64 (ddd, J4 ;5 8.8, J5 ;6
2.3, 4.8, H50), 4.04 (dd, J6 ;6 12.4, H60), 4.13 (dd, J2,3
0
0
7.8, H3), 4.23–4.27 (m, H6,60), 4.34 (ddd, J5,6 1.9, 4.2,
(a) NaOMe (10%) in MeOH (5 mL) was added to the D-
galactosyl fluoride 14 (60 mg, 0.17 mmol) and the thio-
glycoside 9 (75 mg, 0.14 mmol) in MeOH (3 mL) and
the mixture treated as for the preparation of 11 (b).
Flash chromatography (EtOAc/petrol 1:4–1:1) gave
disaccharide 15 as a colourless oil (105 mg, 80%),
[a]D = ꢀ37.7 (c 1, CHCl3). Found: C, 51.8; H, 5.5.
C32H40O16S2 requires C, 51.6; H, 5.4. 1H NMR
(600 MHz): d 1.98, 2.01, 2.04, 2.08, 2.14, 2.22 (6 · s,
21H, CH3CO), 2.29 (s, CH3COS), 3.21 (dd, J3,4 10.1,
H5), 4.40 (dd, J6,6 12.0, H6), 4.68 (d, J1 ;2 8.0, H10),
0
0
4.69 (d, J1,2 10.2, H1), 4.96 (dd, J2 ;3 7.9, H20), 4.99
0
0
(dd, H2), 5.06 (dd, J3 ;4 10.3, H40), 5.12 (dd, H30),
0
0
7.27–7.31, 7.41–7.45 (2 · m, Ph). 13C NMR
(125.7 MHz):
d 20.43, 20.55, 20.76, 20.84, 21.15
(CH3CO), 30.66 (CH3COS), 45.77 (C4), 61.92 (C60),
63.99 (C6), 68.21 (C40), 70.84 (C20), 71.85 (C50), 72.97
(C30), 73.47 (C2), 75.38 (C3), 76.07 (C5), 86.40 (C1),
100.51 (C10), 127.89, 128.87, 132.01, 133.19 (Ph),
169.19, 169.41, 169.64, 170.33, 170.62, 170.70 (6 · C,
C@O), 194.2 (SC@O). HR-MS (FAB) m/z 745.1862
[C32H41O16S2 (M+H)+ requires 745.1836].
J4,5 10.3, H4), 3.85 (ddd, J4 ;5 1.1, J5 ;6 6.7, H50), 4.05
0
0
0
0
(dd, J6 ;6 11.3, H60), 4.09 (dd, H60), 4.12 (dd, J2,3 9.9,
H3), 4.25 (dd, J5,6 5.6, J6,6 12.1, H6), 4.32 (ddd, J5,6
0
0
2.0, H5), 4.40 (dd, H6), 4.64 (d, J1 ;2 8.1, H10), 4.69 (d,
0
0
J1,2 10.1, H1), 4.92 (dd, J2 ;3 10.5, J3 ;4 3.5, H30), 5.00
(dd, H2), 5.14 (d, H20), 5.36 (dd, H40), 7.28–7.31,
7.45–7.48 (2 · m, Ph). 13C NMR (150.8 MHz): d 20.51,
20.53, 20.64, 20.68, 20.80, 21.13 (CH3CO), 30.7
(CH3COS), 46.33 (C4), 61.19 (C60), 64.03 (C6), 66.89
0
0
0
0
(b) NaOMe (10%) in MeOH (2 mL) was added to the D-
glucosyl fluoride 12 (60 mg, 0.17 mmol) and the thioace-
tate 9 (75 mg, 0.14 mmol) in MeOH (3 mL) and the
solution stirred (rt, 30 min). The mixture was quenched
with resin (Amberlite IR-120, H+), filtered and concen-

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
329
(C40), 68.38 (C20), 70.64 (C50), 71.05 (C30), 73.49 (C2),
3.6. Phenyl 2,3,6-tri-O-acetyl-4-deoxy-1-thio-b-D-xylo-
hexoside 20
75.45 (C3), 76.28 (C5), 86.41 (C1), 100.88 (C10),
127.84, 128.85, 131.97, 133.24 (Ph), 169.16, 169.65,
170.19, 170.48, 170.65, 170.87 (C@O), 194.3 (SC@O).
HR-MS (FAB) m/z 745.1858 [C32H41O16S2 (M+H)+ re-
quires 745.1836].
(a) Boron trifluoride diethyl etherate (10 lL) was added
to tetra-O-acetyl-4-deoxy-a-D-xylo-hexopyranose20 (160
mg, 0.48 mmol) and PhSH (0.15 lL, 1.4 mmol) in
CH2Cl2 (5 mL) and the solution stirred (rt, 2 h). Stan-
dard work-up (CH2Cl2) and flash chromatography
(EtOAc/petrol 1:4) gave triacetate 20 as colourless nee-
dles (150 mg, 83%), mp 53–57 ꢁC (Et2O), [a]D = +4.6 (c
1, CHCl3). Found: C, 56.4; H, 5.7. C18H22O7S requires
C, 56.5; H, 5.8. 1H NMR (500 MHz): d 2.02, 2.08,
2.10 (3 · s, 9H, CH3), 2.09 (m, H4), 2.16 (m, J3,4 9.3,
J4,5 9.1, H4), 3.79 (ddd, J4,5 2.0, J5,6 4.1, 6.3, H5), 4.13
(dd, J6,6 11.7, H6), 4.17 (dd, H6), 4.66 (d, J1,2
9.9, H1), 4.92 (dd, J2,3 10.0, H2), 5.03 (ddd, J3,4 5.3,
H3), 7.28–7.32, 7.48–7.53 (2 · m, Ph). 13C NMR
(125.7 MHz): d 20.76, 20.86, 20.91 (3 · C, CH3), 32.57
(C4), 65.38 (C6), 70.53 (C2), 71.69 (C3), 73.34 (C5),
86.08 (C1), 127.99, 128.83, 132.56, 132.65 (Ph), 169.66,
170.26, 170.61 (3 · C, C@O). HR-MS (FAB) m/z
383.1174 [C18H23O7S (M+H)+ requires 383.1164].
(b) (i) Phenyl 2,3,6-tri-O-acetyl-1,4-dithio-b-D-glucoside,
disulfide 16: NaOMe (10%) in MeOH (2 mL) was added
to thioacetate 9 (75 mg, 0.14 mmol) in MeOH (2 mL)
and the solution stirred (rt, 1 h). The mixture was
quenched with resin (Amberlite IR-120, H+), filtered
and concentrated. The residue was dissolved in CHCl3
(5 mL). Triethylamine (15 mg, 0.14 mmol) and I2
(20 mg, 0.07 mmol) were added and the solution stirred
(rt, 45 min). Pyridine (5 mL) and Ac2O (5 mL) were then
added and the solution stirred (rt, 1 h). The reaction was
quenched with MeOH (5 mL) and the solution concen-
trated and subjected to a standard work-up (CHCl3).
Flash chromatography (EtOAc/petrol 3:7) gave the
disulfide 16 as colourless needles (46 mg, 81%), mp
126–128 ꢁC (Et2O), [a]D = ꢀ133.6 (c 1, CHCl3). Found:
C, 52.0; H, 5.0. C36H42O14S4 requires C, 52.3; H, 5.1. 1H
NMR (300 MHz): d 1.91, 2.07 (2 · s, 9H, CH3), 2.91
(dd, J3,4 10.8, J4,5 10.5, H4), 3.72 (ddd, J5,6 1.9, 5.3,
H5), 4.25 (dd, J6,6 12.1, H6), 4.64 (dd, H6), 4.68 (d,
J1,2 10.1, H1), 4.85 (dd, J2,3 8.8, H2), 5.17 (dd, H3),
7.27–7.33, 7.46–7.51 (2 · m, Ph). 13C NMR
(125.7 MHz): d 20.51, 20.70, 20.72 (3 · C, CH3), 51.78
(C4), 63.15 (C6), 70.99 (C2), 72.67 (C5), 76.75 (C3),
85.18 (C1), 128.36, 128.81, 131.51, 133.32 (Ph), 169.46,
169.63, 170.39 (3 · C, C@O). HR-MS (FAB) m/z
827.1518 [C36H43O14S4 (M+H)+ requires 827.1522].
(b) (i) Phenyl tri-O-acetyl-4-O-phenoxythiocarbonyl-1-
O-Phenyl
thio-b-D-galactoside:
chlorothioformate
(0.30 mL, 2.2 mmol) and pyridine (0.36 lL, 4.4 mmol)
were added to phenyl 2,3,6-tri-O-acetyl-1-thio-b-D-
galactopyranoside (200 mg, 0.40 mmol) in CH2Cl2
(20 mL) and the solution stirred (rt, 24 h). The mixture
was quenched with MeOH (5 mL), then concentrated,
followed by a standard work-up (CH2Cl2) and flash
chromatography (EtOAc/petrol 1:4) to give the title thio-
carbonate as a colourless oil (153 mg, 59%), [a]D = ꢀ16.0
1
(c 1, CHCl3). H NMR (300 MHz): d 2.08, 2.13, 2.15
(ii) NaOMe (10%) in MeOH (5 mL) was added to D-
galactosyl fluoride 14 (42 mg, 0.12 mmol) and the disul-
fide 16 (40 mg, 0.05 mmol) in MeOH (3 mL) and the
solution stirred (rt, 30 min). The mixture was quenched
with resin (Amberlite IR-120, H+), filtered and concen-
trated. The residue was dissolved in NH4HCO3 solution
(2 mL of 150 mM), and Abg E358S (2 mg) was added
and the solution kept at 25 ꢁC for 2 h. This was followed
by the addition of 1,4-dithioerythritol (10 mg,
0.06 mmol) and the solution kept (25 ꢁC, 2 h). The solu-
tion was then concentrated and the residue dissolved in
pyridine (5 mL), then Ac2O (5 mL) was added and the
solution stirred (rt, 12 h). The mixture was quenched
by the addition of MeOH (5 mL), concentrated and sub-
jected to a standard work-up (CH2Cl2). Flash chroma-
tography (EtOAc/petrol 1:4–1:1) gave the disaccharide
(3 · s, 9H, CH3), 4.21 (ddd, J4,5 1.0, J5,6 6.1, 6.1, H5),
4.51 (dd, J6,6 11.5, H6), 4.61 (dd, H6), 4.83 (d, J1,2 7.2,
H1), 5.28 (dd, J2,3 9.9, J3,4 3.3, H3), 5.39 (dd, H2), 6.20
(dd, H4), 7.12–7.21, 8.05–8.12 (2 · m, Ph). 13C NMR
(75.5 MHz): d 20.74, 20.81, 20.83 (3 · C, CH3), 61.86
(C6), 67.37 (C2), 71.66 (C3), 74.52 (C5), 77.11 (C4),
87.04 (C1), 121.58, 128.01, 128.94, 129.25, 129.60,
132.71, 133.34, 153.38 (Ph), 165.91, 169.37, 170.01
(3 · C, C@O), 195.41 (C@S). HR-MS (FAB) m/z
535.2964 [C25H27O9S2 (M+H)+ requires 535.2975].
(ii) Tributylstannane (0.28 mL, 1.1 mmol) was added to
the above thiocarbonate (160 mg, 0.27 mmol) and
AIBN (20 mg) in dry PhMe (15 mL) and the mixture
stirred (60 ꢁC, 4 h). Concentration of the mixture and
flash chromatography (EtOAc/petrol 17:83) of the resi-
due gave the triacetate 20 as colourless needles (85 mg,
1
15 as a colourless oil (21 mg, 30%). The H and 13C
1
NMR spectra were consistent with those reported in (a).
73%). The H NMR spectrum was consistent with that
reported in (a).
3.5. Phenyl tetra-O-acetyl-b-D-galactopyranosyl-(1!4)-
2,3,6-tri-O-acetyl-1-thio-b-D-glucoside 18
3.7. Phenyl tetra-O-acetyl-b-D-glucopyranosyl-(1!4)-tri-
O-acetyl-b-D-glucopyranosyl-(1!3)-2,6-di-O-acetyl-4-de-
oxy-1-thio-b-D-xylo-hexoside 21 and phenyl tetra-O-ace-
tyl-b-D-glucopyranosyl-(1!4)-tri-O-acetyl-b-D-glucopyr-
anosyl-(1!4)-tri-O-acetyl-b-D-glucopyranosyl-(1!3)-2,6-
di-O-acetyl-4-deoxy-1-thio-b-D-xylo-hexoside 22
NaOMe (10%) in MeOH (5 mL) was added to D-galac-
tosyl fluoride 14 (60 mg, 0.17 mmol) and thioglycoside
17 (62 mg, 0.14 mmol) in MeOH (3 mL) and the mixture
treated as for the preparation of 11 (b). Flash chroma-
tography (EtOAc/petrol 1:4–1:1) gave disaccharide 18
as a colourless oil (92 mg, 74%). The 1H and 13C
NMR spectra were consistent with those reported.19
According to the procedure described for 11 (b) but
leaving the reaction for 48 h, 12 (60 mg, 0.17 mmol)

330
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
0
0
0
0
0
and 20 (75 mg, 0.20 mmol) gave the trisaccharide 21 as
colourless plates (49 mg, 26%), mp 89–91 ꢁC (EtOH),
[a]D = ꢀ21.3 (c 1, CHCl3). Found: C, 52.4; H, 5.7.
C42H54O23S requires C, 52.6; H, 5.7. 1H NMR
(500 MHz): d 1.97, 1.99, 2.00, 2.01, 2.02, 2.07, 2.09,
2.10, 2.12 (9 · s, 27H, CH3), 2.10–2.19 (m, 2H, H4),
(m, 2H, H4), 3.73 (m, H5), 3.83 (ddd, J4 ;5 1.0, J5 ;6
6.3, 7.0, H50), 3.88 (m, J2,3 9.3, H3), 4.08 (dd, J6 ;6
0
11.3, H60), 4.14 (dd, J5,6 6.5, J6,6 11.7, H6), 4.16 (dd,
J5,6 3.7, H6), 4.20 (dd, H60), 4.56 (d, J1,2 10.0, H1),
4.60 (d, J1 ;2 8.1, H10), 4.88 (dd, H2), 4.95 (dd, J2 ;3
0
0
0
0
10.5, J3 ;4 3.4, H30), 5.15 (dd, H20), 5.37 (dd, H40),
7.28–7.30, 7.46–7.49 (2 · m, Ph). 13C NMR
(150.8 MHz): d 20.51, 20.55, 20.65, 20.79, 21.60 (CH3),
34.57 (C4), 61.05 (C60), 65.56 (C6), 66.83 (C40), 68.41
(C20), 70.62, 70.81 (C2,50), 72.30 (C30), 73.63 (C5),
77.56 (C3), 86.28 (C1), 101.73 (C10), 127.75, 128.78,
132.08, 133.21 (Ph), 169.22, 169.47, 170.24, 170.26,
170.38, 170.71 (6 · C, C@O). HR-MS (FAB) m/z
671.1970 [C30H39O15S (M+H)+ requires 671.2010].
0
0
3.53 (ddd, J4 ;5 9.9, J5 ;6 2.2, 4.6, H50), 3.65 (ddd, J4 ;5
0
0
0
0
00 00
9.9, J5 ;6 2.3, 4.4, H500), 3.68–3.77 (m, H3,5,40), 4.03
00 00
(dd, J6 ;6 12.5, H600), 4.06 (dd, J6 ;6 12.1, H60), 4.11
(dd, J5,6 6.2, J6,6 11.8, H6), 4.15 (dd, J5,6 3.9, H6), 4.35
00 00
0
0
(dd, H600), 4.50 (d, J1 ;2 7.9, H100), 4.54 (d, J1,2 10.0,
00 00
H1), 4.55 (m, H60), 4.58 (d, J1 ;2 8.0, H10), 4.82 (dd,
0
0
J2 ;3 9.1, H20), 4.84 (dd, J2,3 9.5, H2), 4.91 (dd, J2 ;3
0
0
00 00
9.4, H200), 5.05 (dd, J3 ;4 9.7, H400), 5.11 (dd, H300),
00 00
5.14 (dd, J3 ;4 9.7, H30), 7.26–7.31, 7.45–7.48 (2 · m,
Ph). 13C NMR (125.7 MHz): d 20.37, 20.48, 20.59,
20.74, 20.80, 21.00 (CH3), 34.45 (C4), 61.23 (C60),
61.48 (C600), 65.55 (C6), 67.73 (C400), 71.16 (C20), 71.58
(C200), 71.95 (C500), 72.10 (C2), 72.43 (C300), 72.71
(C50), 72.83 (C30), 73.60 (C5), 76.21, 77.92 (C3,40),
86.21 (C1), 100.76 (C100), 101.12 (C10), 127.74, 128.76,
132.12, 133.14 (Ph), 168.96, 169.19, 169.26, 169.60,
169.77, 170.07, 170.17, 170.43, 170.67 (9 · C, C@O).
HR-MS (FAB) m/z 959.2928 [C42H55O23S (M+H)+ re-
quires 959.2855].
0
0
3.9. Attempted synthesis of the 3-deoxy sugar 19
(i) Phenyl 4-O-acetyl-2,6-di-O-benzoyl-1-thio-b-D-galac-
toside 25: Trifluoroacetic acid (one drop) was added to
phenyl 2,6-di-O-benzoyl-1-thio-b-D-galactopyranoside21
(500 mg, 1.0 mmol) and CH3C(OEt)3 (510 mg,
3.1 mmol) in CHCl3 (5 mL) and the solution stirred
(rt, 5 min). Acetonitrile (5 mL) and H2O (1 mL) were
then added and the mixture stirred vigourously (rt,
30 min). Concentration of the mixture, followed by flash
chromatography (EtOAc/petrol 3:7), gave acetate 25 as
needles (510 mg, 95%), mp 177–179 ꢁC (EtOH),
Next to elute was tetrasaccharide 22 as colourless plates
(27 mg, 11%), mp 109–111 ꢁC (EtOH), [a]D = +2.7 (c 1,
1
[a]D = +0.1 (c 1, CHCl3). H NMR (500 MHz): d 2.21
1
CHCl3). H NMR (600 MHz): d 1.96, 1.97, 1.99, 2.00,
(s, CH3), 2.71 (s, OH), 4.06 (dd, J5,6 5.2, 7.6, H5), 4.11
(dd, J2,3 9.8, J3,4 3.5, H3), 4.44 (dd, J6,6 11.5, H6), 4.50
(dd, H6), 4.90 (d, J1,2 10.0, H1), 5.30 (dd, H2), 5.52
(d, H4), 7.12–7.21, 7.45–7.60, 8.05–8.08 (3 · m, 15H,
Ph). 13C NMR (125.7 MHz): d 20.73 (CH3), 62.69
(C6), 69.99 (C3), 71.59, 72.62 (C2,5), 74.95 (C4), 86.43
(C1), 127.96–133.54 (Ph), 166.03, 166.70, 170.82
(3 · C, C@O). HR-MS (FAB) m/z 523.1407
[C28H27O8S (M+H)+ requires 523.1426].
2.01, 2.03, 2.07, 2.08, 2.11, 2.12, 2.13 (11 · s, 36H,
0
0
0
0
CH3), 2.00–2.08 (m, 2H, H4), 3.52 (ddd, J4 ;5 9.9, J5 ;6
2.2, 4.4, H50), 3.57 (ddd, J4 ;5 9.8, J5 ;6 2.1, 5.1, H500),
00 00
00 00
3.62 (ddd, J4
9.9, J5
2.4, 4.4, H5000), 3.70–3.77
000;5000
000;6000
(m, H3,5,40, 400), 4.02 (dd, J6
11.0, H6000), 4.04 (dd,
000;6000
J6 ;6 10.3, H60), 4.11 (dd, J6 ;6 12.1, H600), 4.13–4.17
0
0
00 00
(m, 2H, H6), 4.34 (dd, H6000), 4.39 (dd, H600), 4.46 (d,
7.9, H1000), 4.47 (d, J1 ;2 7.9, H10), 4.54 (d, J1,2
0
0
000;2000
J1
10.0, H1), 4.57 (d, J1 ;2 8.0, H100), 4.58 (dd, H60), 4.82
00 00
(dd, J2,3 9.6, H2), 4.83 (dd, J2 ,3 9.2, H20), 4.84 (dd,
(ii) Phenyl 4-O-acetyl-2,6-di-O-benzoyl-3-O-phenoxy-
thiocarbonyl-1-thio-b-D-galactoside: O-Phenyl chloro-
thioformate (0.15 mL, 1.1 mmol) and pyridine
(0.70 lL, 0.90 mmol) were added to acetate 25
(150 mg, 0.30 mmol) in CH2Cl2 (20 mL) and the solu-
tion stirred (rt, 24 h). The mixture was quenched with
MeOH (5 mL), then concentrated, followed by a stan-
dard workup (CH2Cl2) and flash chromatography
(EtOAc/petrol 1:4) to give the title thiocarbonate as a
colourless oil (150 mg, 79%), [a]D = +57.3 (c 1, CHCl3).
1H NMR (500 MHz): d 2.02 (s, CH3), 4.23 (ddd, J4,5 1.0,
J5,6 4.2, 5.2, H5), 4.43 (dd, J6,6 11.5, H6), 4.55 (dd, H6),
5.00 (d, J1,2 10.0, H1), 5.73 (dd, J2,3 10.0, H2), 5.85 (dd,
J3,4 3.4, H4), 5.90 (dd, H3), 6.90–7.60, 8.00–8.10 (2 · m,
20H, Ph). 13C NMR (125.7 MHz): d 20.58 (CH3), 62.43
(C6), 66.70, 67.98 (C2,4), 74.73 (C5), 80.94 (C3), 87.05
(C1), 121.48–133.59 (Ph), 165.06, 165.93, 169.98
(3 · C, C@O), 193.16 (C@S). HR-MS (FAB) m/z
659.1411 [C35H31O9S2 (M+H)+ requires 659.1409].
0
0
J2 ;3 9.2, H200), 4.89 (dd, J2
9.3, H2000), 5.04 (dd,
00 00
000;3000
J3
9.4, H4000), 5.09 (dd, J3 ;4 9.4, H30), 5.12 (dd,
000;4000
0
0
J3 ;4 9.2, H300), 5.13 (dd, J3
9.5, H3000), 7.25–7.30,
000;4000
00 00
7.45–7.47 (2 · m, Ph). 13C NMR (150.8 MHz): d 20.40,
20.45, 20.49, 20.51, 20.53, 20.56, 20.60, 20.75, 20.77,
20.84, 21.02 (CH3), 34.44 (C4), 61.08 (C60), 61.45
(C6000), 62.06 (C600), 65.54 (C6), 67.67 (C4000), 71.20
(C2), 71.51 (C2000), 71.72, 71.98 (C20, 200), 72.09 (C5000),
72.35 (C30), 72.58 (C300), 72.73 (C50,500), 72.82 (C3000),
73.59 (C40), 76.07, 77.89 (C3,5), 76.21 (C400), 86.19
(C1), 100.57, 100.76 (C10, 1000), 101.09 (C100), 127.74,
128.76, 132.09, 133.15 (Ph), 169.08, 169.22, 169.24,
169.28, 169.59, 169.76, 169.80, 170.10, 170.17, 170.18,
170.47, 170.72 (12 · C, C@O). HR-MS (FAB) m/z
1247.3717 [C54H71O31S (M+H)+ requires 1247.3700].
3.8. Phenyl tetra-O-acetyl-b-D-galactopyranosyl-(1!3)-
2,6-di-O-acetyl-4-deoxy-1-thio-b-D-xylo-hexoside 24
According to the procedure described for 11 (b), 14
(60 mg, 0.17 mmol) and 20 (53 mg, 0.14 mmol) gave
disaccharide 24 as a colourless oil (79 mg, 85%),
[a]D = ꢀ20.8 (c 1, CHCl3). 1H NMR (600 MHz): d
1.97, 2.00, 2.01, 2.09, 2.12 (5 · s, 18H, CH3), 2.10–2.16
(iii) Phenyl 4-O-acetyl-2,6-di-O-benzoyl-3-deoxy-1-thio-
b-D-xylo-hexoside: Tributylstannane (0.2 mL, 0.8 mmol)
was added to the above thiocarbonate (140 mg,
0.21 mmol) and AIBN (20 mg) in dry PhMe (15 mL)
and the mixture stirred (60 ꢁC, 3 h). Concentration of

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
331
the mixture, followed by flash chromatography (EtOAc/
petrol 17:83), gave the title D-xylo-hexoside as colourless
plates (80 mg, 75%), mp 118–121 ꢁC (EtOH),
[a]D = ꢀ12.6 (c 1, CHCl3). 1H NMR (500 MHz): d
1.95 (ddd, J2,3 11.2, J3,3 14.0, J3,4 3.1, H3), 2.03 (s,
CH3), 2.64 (ddd, J2,3 3.3, J3,4 5.1, H3), 4.11 (ddd, J4,5
1.4, J5,6 5.1, 7.6, H5), 4.45 (dd, J6,6 11.5, H6), 4.50
(dd, H6), 4.98 (d, J1,2 10.0, H1), 5.30–5.33 (m, H2,4),
7.11–7.41, 7.52–7.64, 8.03–8.06 (3 · m, 15H, Ph). 13C
NMR (125.7 MHz): d 20.89 (CH3), 34.53 (C3), 63.10
(C6), 66.42, 67.32 (C2,4), 76.74 (C5), 88.22 (C1),
127.62–133.24 (Ph), 165.04, 166.04, 170.15 (3 · C,
C@O). HR-MS (FAB) m/z 506.1399 [C28H26O7S (M)+
requires 506.1399].
and the solution stirred (30 min). Saturated NaHCO3
solution (5 mL) was added and, after a standard work-
up (CH2Cl2), potassium thioacetate (190 mg, 1.7 mmol)
was added to the residue in dry THF (10 mL) and the
mixture stirred (rt, 16 h). Filtration and concentration
of the mixture, followed by a standard work-up
(CH2Cl2) and flash chromatography (EtOAc/petrol
1:4), gave alkene 28 as a colourless oil (184 mg, 64%).
The 1H NMR spectrum was consistent with that report-
ed above.
(vii) Diethyl azodicarboxylate (0.15 mL, 0.70 mmol) was
added to dibenzoate 26 (150 mg, 0.33 mmol), Ph3P
(170 mg, 0.70 mmol) and CH3C(O)SH (50 mg,
0.10 mmol) in PhMe (5 mL) and the mixture stirred
(50 ꢁC, 6 h). Another set of the three reagents was added
to the solution after 6 h and again after 24 h, with sub-
sequent stirring for 6 h. Concentration of the mixture,
followed by flash chromatography (EtOAc/petrol
17:83), gave alkene 28 as a colourless oil (70 mg,
(iv) Phenyl 2,6-di-O-benzoyl-3-deoxy-1-thio-b-D-xylo-
hexopyranoside 26: Acetyl chloride (0.44 mL, 6.1 mmol)
was added to the above D-xylo-hexoside (1.1 g,
2.3 mmol) in MeOH (60 mL) and the solution stirred
(rt, 24 h). The solution was neutralised with resin
(Amberlite IRA 400, OHꢀ), filtered and concentrated.
Flash chromatography (EtOAc/petrol 1:4) gave di-
benzoate 26 as colourless needles (751 mg, 74%), mp
165–168 ꢁC (EtOH), [a]D = ꢀ5.4. Found: C, 67.3; H,
5.3. C26H24O6S requires C, 67.2; H, 5.2. 1H NMR
(500 MHz): d 1.90 (ddd, J2,3 11.3, J3,3 13.6, J3,4 3.0,
H3), 2.45 (s, OH), 2.65 (ddd, J2,3 5.1, J3,4 3.2, H3),
4.00 (ddd, J4,5 1.2, J5,6 5.1, 7.4, H5), 4.03 (ddd, H4),
4.53 (dd, J6,6 11.7, H6), 4.69 (dd, H6), 4.95 (d, J1,2
10.0, H1), 5.38 (ddd, H2), 7.10–7.20, 7.41–7.59, 8.04–
8.09 (3 · m, 15H, Ph). 13C NMR (125.7 MHz): d 37.36
(C3), 63.86 (C6), 66.00 (C2), 66.55 (C4), 78.49 (C5),
88.42 (C1), 127.57–133.34 (Ph), 165.3, 166.5 (2 · C,
C@O). HR-MS (FAB) m/z 465.1380 [C26H25O6S
(M+H)+ requires 465.1372].
1
49%). The H NMR spectrum was consistent with that
reported in (v).
3.10. Phenyl 2,6-di-O-benzoyl-4-O-chloroacetyl-3-deoxy-
1-thio-b-D-ribo-hexoside 29
Diethyl azodicarboxylate (0.1 mL, 0.4 mmol) was added
to dibenzoate 26 (100 mg, 0.20 mmol), Ph3P (114 mg,
0.44 mmol) and ClCH2CO2H (40 mg, 0.40 mmol) in
PhMe (5 mL) and the mixture stirred (rt, 3 h). Concen-
tration of the mixture, followed by flash chromatogra-
phy (EtOAc/petrol 17:83), gave chloroacetate 29 as a
colourless oil (81 mg, 72%), [a]D = ꢀ10.5 (c 1, CHCl3).
1H NMR (500 MHz): d 1.86 (ddd, J2,3 10.9, J3,3 11.8,
J3,4 10.8, H3), 2.86 (ddd, J2,3 5.0, J3,4 4.9, H3), 3.96
(ddd, J4,5 9.8, J5,6 2.5, 5.7, H5), 4.03, 4.04 (2 · s, CH2),
4.43 (dd, J6,6 12.1, H6), 4.64 (dd, H6), 4.89 (d, J1,2 9.9,
H1), 5.01–5.04 (m, H2,4), 7.13–7.15, 7.21–7.24, 7.45–
7.51, 7.58–7.64, 8.05–8.07 (5 · m, 15H, Ph). 13C NMR
(125.7 MHz): d 34.98 (C3), 40.49 (CH2), 62.99 (C6),
67.54, 67.71 (C2,4), 77.77 (C5), 87.19 (C1), 128.11–
133.36 (Ph), 164.88, 165.96, 166.12 (3 · C, C@O).
HR-MS (FAB) m/z 543.1030 [C28H26ClO7S (M+H)+ re-
quires 543.1058].
(v) Trifluoromethanesulfonic anhydride (0.13 mL,
0.75 mmol) was added to dibenzoate 26 (310 mg,
0.67 mmol) in CH2Cl2 (10 mL) and pyridine (200 lL,
2.0 mmol) at ꢀ30 ꢁC and the solution stirred (30 min).
Saturated NaHCO3 solution (5 mL) was added and,
after a standard work-up (CH2Cl2), potassium thioace-
tate (190 mg, 1.7 mmol) was added to the residue, pre-
sumably triflate 27, in dry THF (10 mL) and the
mixture stirred (rt, 16 h). Filtration and concentration
of the mixture, followed by a standard workup (CH2Cl2)
and flash chromatography (EtOAc/petrol 1:4), gave
3.11. Phenyl 2,6-di-O-benzoyl-3-deoxy-1-thio-b-D-ribo-
hexopyranoside 30
1
alkene 28 as a colourless oil (175 mg, 59%). H NMR
(600 MHz): d 4.48 (dd, J5,6 6.3, J6,6 11.5, H6), 4.53
(dd, J5,6 4.2, H6), 4.74 (m, J3,5 2.1, J4,5 1.3, H5), 5.13
(d, J1,2 8.2, H1), 5.58 (m, J2,3 2.1, J2,4 1.3, H2), 5.98
(ddd, J3,4 10.3, H4), 6.03 (ddd, H3), 7.20–7.26, 7.44–
7.60, 8.02–8.08 (3 · m, 15H, Ph). 13C NMR
(150.8 MHz): d 65.73 (C6), 67.19 (C2), 73.96 (C5),
84.30 (C1), 127.39, 127.87, 128.40, 128.45, 128.81,
129.71, 129.72, 129.77, 129.81, 132.57, 132.66, 133.17,
133.28 (C3,4, Ph), 165.60, 166.24 (2 · C, C@O). HR-
MS (FAB) m/z 447.1244 [C26H33O5S (M+H)+ requires
447.1266].
Chloroacetate 29 (80 mg, 0.15 mmol) was added to
H2NCSNH2 (110 mg, 1.5 mmol) and 2,6-lutidine
(0.02 mL, 0.15 mmol) in MeOH/CH2Cl2 (10 mL, 1:1)
and the mixture stirred (35 ꢁC, 12 h). Concentration of
the mixture, followed by flash chromatography
(EtOAc/petrol 1:4), gave alcohol 30 as colourless plates
(63 mg, 87%), mp 142–143 ꢁC (EtOH), [a]D = ꢀ73.7 (c 1,
CHCl3). 1H NMR (600 MHz): d 1.78 (ddd, J2,3 11.0, J3,3
12.1, J3,4 11.0, H3), 2.70 (ddd, J2,3 ꢁ J3,4 4.9, H3), 3.05
(s, OH), 3.64 (ddd, J4,5 9.4, J5,6 2.2, 4.6, H5), 3.70–
3.72 (m, H4), 4.63 (dd, J6,6 12.1, H6), 4.78 (dd, H6),
4.85 (d, J1,2 9.8, H1), 4.92 (ddd, H2), 7.15–7.18, 7.22–
7.25, 7.46–7.50, 7.58–7.63, 8.05–8.09 (5 · m, Ph). 13C
NMR (150.8 MHz): d 38.12 (C3), 63.79 (C6), 64.46,
68.29 (C2,4), 81.19 (C5), 87.11 (C1), 127.88–133.43
(vi) Methanesulfonyl chloride (0.060 mL, 0.75 mmol)
was added to dibenzoate 26 (300 mg, 0.64 mmol) in
CH2Cl2 (10 mL) and Et3N (0.28 mL, 2.0 mmol) at 0 ꢁC

332
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
(Ph), 165.18, 167.34 (2 · C, C@O). HR-MS (FAB) m/z
(m, H2,4), 7.27–7.34, 7.47–7.51 (2 · m, Ph). 13C NMR
(150.8 MHz): d 20.53, 20.71, 20.75 (3 · C, CH3CO),
30.66 (CH3COS), 49.42 (C3), 62.43 (C6), 67.23, 69.12,
78.00 (C2,4,5), 87.64 (C1), 128.18, 128.87, 132.12,
132.74 (Ph), 170.64, 169.31, 170.64 (3 · C, C@O),
193.36 (SC@O). HR-MS (FAB) m/z 457.0986
[C20H25O8S2 (M+H)+ requires 457.0990].
465.1378 [C26H25O6S (M+H)+ requires 465.1372].
3.12. Phenyl 4-S-acetyl-2,6-di-O-benzoyl-3-deoxy-1,4-
dithio-b-D-xylo-hexoside
Diethyl azodicarboxylate (0.30 mL, 0.26 mmol) was
added to alcohol 30 (60 mg, 0.13 mmol), Ph3P
(67 mg, 0.26 mmol) and CH3C(O)SH (19 mg,
0.26 mmol) in PhMe (5 mL) and the mixture stirred
(rt, 4 h). Concentration of the mixture, followed by
flash chromatography (EtOAc/petrol 1:9), gave the title
(iii) 4-Nitrophenyl 2,4,6-tri-O-acetyl-3-S-acetyl-3-thio-b-
D-glucoside 35: Boron trifluoride diethyl etherate
(10 lL) was added to the above thioacetate (160 mg,
0.48 mmol) and 4-nitrophenol (72 mg, 0.52 mmol) in
CH2Cl2 (5 mL) and the solution stirred (rt, 96 h). The
mixture was quenched with Et3N (5 mL) and subsequent
concentration and flash chromatography (EtOAc/tolu-
ene 1:9) yielded thioacetate 35 as a colourless oil
(136 mg, 71%), [a]D = ꢀ8.1 (c 1, CHCl3). 1H NMR
(500 MHz): d 2.04, 2.05, 2.08 (3 · s, 9H, CH3CO), 2.37
(s, CH3COS), 3.97 (dd, J2,3 10.0, J3,4 9.9, H3), 3.99
(ddd, J4,5 10.9, J5,6 2.5, 5.5, H5), 4.16 (dd, J6,6 12.4,
H6), 4.25 (dd, H6), 5.15 (dd, H4), 5.22 (d, J1,2 7.3,
H1), 5.30 (dd, H2), 7.16, 8.20 (AA0BB0, 4H, Ar). 13C
NMR (125.7 MHz): d 20.51, 20.55, 20.67 (3 · C,
CH3CO), 30.63 (CH3COS), 47.39 (C3), 62.11 (C6),
67.09, 69.80, 75.05 (C2,4,5), 99.27 (C1), 116.58, 125.77,
134.46, 161.18 (Ar), 169.08, 169.26, 170.47 (3 · C,
C@O), 193.19 (SC@O). HR-MS (FAB) m/z 487.2083
[C20H24NO11S (M+H)+ requires 487.2087].
thioacetate as
a
colourless oil (53 mg, 79%),
[a]D = ꢀ14.0 (c 1, CHCl3). Found: C, 64.4; H, 5.1.
C28H26O6S2 requires C, 64.3; H, 5.0. 1H NMR
(600 MHz): d 2.24 (ddd, J2,3 10.4, J3,3 13.5, J3,4 4.9,
H3), 2.39 (s, CH3), 2.54 (ddd, J2,3 4.9, J3,4 2.1, H3),
4.19 (ddd, J4,5 1.5, H4), 4.26 (ddd, J5,6 4.4, 7.7, H5),
4.38 (dd, J6,6 11.7, H6), 4.49 (dd, H6), 4.94 (d, J1,2
9.9, H1), 5.11 (ddd, H2), 7.11–7.14, 7.18–7.23, 7.44–
7.48, 7.57–7.61, 8.01–8.04 (5 · m, 15H, Ph). 13C
NMR (150.8 MHz): d 30.87 (CH3), 37.23 (C3), 41.80
(C4), 64.87 (C6), 67.51 (C2), 77.97 (C5), 88.58 (C1),
127.69–133.38 (Ph), 165.18, 166.13 (2 · C, C@O),
193.94 (SC@O). HR-MS (FAB) m/z 523.1249
[C28H27O6S2 (M+H)+ requires 523.1249].
3.13. Synthesis of the thioacetates 33 and 35
(i) Tetra-O-acetyl-3-S-acetyl-3-thio-b-D-glucopyranose:
3-S-Acetyl-1,2:5,6-di-O-isopropylidene-3-thio-a-D-glu-
cose22 (3.5 g) was added to CF3COOH/H2O (4:1,
15 mL) and the solution stirred (rt, 30 min). Concentra-
tion of the mixture gave a brown residue, which was dis-
solved in Ac2O (20 mL) containing NaOAc (500 mg).
This mixture was heated at reflux (10 min) before being
poured into ice/water. Standard work-up (EtOAc) gave
the title thioacetate as a colourless oil (4.0 g, 90%),
3.14. Phenyl tetra-O-acetyl-b-D-glucopyranosyl-(1!3)-
2,4,6-tri-O-acetyl-1,3-dithio-b-D-glucoside 34
NaOMe (10%) in MeOH (5 mL) was added to thioace-
tate 33 (50 mg, 0.11 mmol) in MeOH (5 mL) and the
solution stirred (rt, 10 min). The mixture was quenched
with resin (Amberlite IR-120, H+), filtered and concen-
trated. The residue was taken up in 80 mM phosphate
buffer (pH 6.8, 5 mL) and the D-glucoside 31 (76 mg,
0.22 mmol) and Abg E171A (2 mg) added and the solu-
tion kept at 25 ꢁC for 24 h. The solution was concen-
trated and the residue dissolved in pyridine (5 mL),
then Ac2O (5 mL) was added and the solution stirred
(rt, 12 h). The mixture was quenched by the addition
of MeOH (5 mL) and concentrated. Standard work-up
(CH2Cl2) and flash chromatography (EtOAc/petrol
1:4–1:1) gave the disaccharide 34 as a colourless oil
(66 mg, 81%), [a]D = ꢀ11.1 (c 1, CHCl3). Found: C,
1
[a]D = +1.2 (c 1, CHCl3). H NMR (600 MHz): d 2.03,
2.08, 2.10 (3 · s, 12H, CH3CO), 2.34 (s, CH3COS),
3.85 (m, J2,3 10.9, J3,4 10.5, H3,5), 4.06 (dd, J5,6 2.3,
J6,6 12.5, H6), 4.26 (dd, J5,6 4.7, H6) 5.10 (m, H2,4),
5.72 (d, J1,2 8.0, H1). 13C NMR (150.8 MHz): d 20.38,
20.47, 20.71, 20.82 (4 · C, CH3CO), 30.73 (CH3COS),
47.70 (C3), 61.76 (C6), 66.76, 69.09, 75.35 (C2,4,5),
93.06 (C1), 168.85, 169.15, 169.26, 170.64 (4 · C,
C@O), 193.06 (SC@O). HR-MS (FAB) m/z 407.1038
[C16H23O10S (M+H)+ requires 407.1011].
1
51.5; H, 5.7. C32H40O16S2 requires C, 51.5; H, 5.5. H
NMR (500 MHz): d 1.98, 2.01, 2.02, 2.06, 2.07, 2.09,
2.16 (7 · s, 21H, CH3), 2.99 (dd, J2,3 9.8, J3,4 9.9, H3),
3.69–3.71 (m, H5,50), 4.13, 4.17, 4.25 (3 · m, 4H,
(ii) Phenyl 2,4,6-tri-O-acetyl-3-S-acetyl-1,3-dithio-b-D-
glucoside 33: Boron trifluoride diethyl etherate (10 lL)
was added to the above thioacetate (470 mg, 1.2 mmol)
and PhSH (0.17 mL, 1.6 mmol) in CH2Cl2 (5 mL) and
the solution stirred (rt, 24 h). The mixture was quenched
with Et3N (5 mL) and subsequent concentration and
flash chromatography (EtOAc/petrol 1:9) yielded thio-
H6,60), 4.61 (d, J1,2 9.8, H1), 4.64 (d, J1 ;2 10.3, H10),
0
0
4.85 (dd, J4,5 10.8, H4), 4.89 (dd, J2 ;3 9.3, H20), 5.03–
0
0
5.07 (m, H2,40), 5.17 (dd, J3 ;4 9.3, H3), 7.28–7.32,
7.46–7.48 (2 · m, Ph). 13C NMR (125.7 MHz): d 20.40,
20.53, 20.72, 20.95 (CH3), 52.29 (C3), 61.93, 62.62
(C6,60), 66.73 (C4), 68.16, 71.73 (C2,40), 70.03 (C20),
73.67 (C30), 75.64, 77.99 (C5,50), 84.32 (C10), 87.91
(C1), 128.08, 128.87, 132.44, 132.63 (Ph), 168.67,
169.12, 169.29, 169.44, 170.91, 170.57 (C@O). HR-MS
(FAB) m/z 745.1832 [C32H41O16S2 (M+H)+ requires
745.1836].
0
0
acetate 33 as
a
colourless oil (470 mg, 89%),
[a]D = ꢀ11.0 (c 1, CHCl3). Found: C, 52.4; H, 5.5.
C20H24O8S2 requires C, 52.6; H, 5.3. 1H NMR
(600 MHz): d 2.01, 2.07, 2.08 (3 · s, 9H, CH3CO), 2.33
(s, CH3COS), 3.74 (ddd, J4,5 9.9, J5,6 2.6, 5.0, H5),
3.86 (dd, J2,3 9.9, J3,4 10.0, H3), 4.16 (dd, J6,6 12.3,
H6), 4.19 (dd, H6), 4.73 (d, J1,2 9.7, H1), 4.99–5.03

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
333
3.15. 4-Nitrophenyl tetra-O-acetyl-b-D-glucopyranosyl-
(1!3)-2,4,6-tri-O-acetyl-3-thio-b-D-glucoside 36
3.17. Phenyl tetra-O-acetyl-b-D-glucopyranosyl-(1!6)-
2,3,4-tri-O-acetyl-1,6-dithio-b-D-glucoside
According to the procedure described for 34, 31 (76 mg,
0.22 mmol) and 35 (53 mg, 0.11 mmol) gave the disaccha-
ride 36 as a colourless oil (46 mg, 58%), [a]D = ꢀ13.1 (c 1,
According to the procedure described for 34, 31 (76 mg,
0.22 mmol) and 37 (50 mg, 0.11 mmol) gave the title
disaccharide as
a
colourless oil (12 mg, 15%),
1
1
CHCl3). H NMR (600 MHz): d 1.99, 2.02, 2.03, 2.06,
[a]D = ꢀ8.4 (c 1, CHCl3). H NMR (600 MHz): d 1.98,
2.00, 2.01, 2.03, 2.05, 2.08, 2.09 (7 · s, 21H, CH3), 2.80
(dd, J5,6 2.9, J6,6 14.0, H6), 2.87 (dd, J5,6 8.6, H6), 3.66
2.08, 2.11, 2.14 (7 · s, 21H, CH3), 3.11 (dd, J2,3 10.5,
J3,4 10.4, H3), 3.73 (ddd, J4 ;5 10.0, J5 ;6 2.5, 5.0, H50),
3.94 (ddd, J4,5 10.7, J5,6 2.4, 5.4, H5), 4.10–4.20, 4.23–
0
0
0
0
(ddd, J4 ;5 10.0, J5 ;6 3.5, 4.3, H50), 3.74 (ddd, J4,5 9.7,
H5), 4.13–4.15 (m, 2H, H60), 4.61, 4.76 (2d, H1,10),
4.90 (dd, J3,4 9.7, H4), 4.95–4.99 (m, 2H, H2,20), 5.05
0
0
0
0
4.29 (2 · m, 4H, H6,60), 4.73 (d, J1 ;2 10.2, H10), 4.93
0
0
(dd, J2 ;3 10.1, H20), 4.98 (dd, J3,4 10.7, H4), 5.07 (dd,
0
0
J3 ;4 9.6, H40), 5.10 (d, J1,2 7.4, H1), 5.20 (dd, H30),
5.37 (dd, H2), 7.15, 8.20 (AA0BB0, 4H, Ar). 13C NMR
(150.8 MHz): d 20.42, 20.54, 20.64, 20.75 (CH3), 49.64
(C3), 62.01, 62.29 (C6,60), 66.42 (C4), 68.17 (C40),
70.10 (C20), 72.04 (C2), 73.61 (C30), 74.90 (C5), 75.69
(C50), 83.70 (C10), 99.29 (C1), 116.51, 125.76, 143.16,
161.17 (Ar), 168.44, 169.14, 169.29, 169.38, 170.16,
170.40, 170.55 (C@O). HR-MS (FAB) m/z 758.2915
[C32H40NO18S (M+H)+ requires 758.2905].
(dd, J3 ;4 10.0, H40), 5.16 (dd, H30), 5.21 (dd, H3),
7.29–7.35, 7.51–7.54 (2 · m, Ph). 13C NMR
(150.8 MHz): d 20.56, 20.58, 20.65, 20.67, 20.73, 20.75
(CH3), 31.24 (C6), 62.01 (C60), 68.25, (C40), 70.01,
70.16 (C2,20), 71.45 (C4), 73.76, 73.77 (C3,30), 75.94
(C50), 78.21 (C5), 83.26, 85.83 (C1,10), 128.30, 129.11,
131.98, 132.53 (Ph), 169.29, 169.36, 169.43, 169.58,
170.10, 170.13, 170.59 (C@O). HR-MS (FAB) m/z
745.1840 [C32H41O16S2 (M+H)+ requires 745.1836].
0
0
0
0
3.16. Synthesis of the thioacetate 37
3.18. Phenyl 3,4,6-tri-O-acetyl-2-S-acetyl-1,2-dithio-b-D-
glucoside 38
(i) Phenyl 2,3,4-tri-O-acetyl-6-O-methanesulfonyl-1-thio-
b-D-glucoside: Triethylamine (1.0 mL, 7.0 mmol) and
MsCl (0.33 mL, 4.2 mmol) were added to phenyl 2,3,4-
tri-O-acetyl-1-thio-b-D-glucoside23 (1.4 g, 3.5 mmol) in
CH2Cl2 (20 mL) and the solution stirred (rt, 1 h). Stan-
dard work-up (CH2Cl2) and flash chromatography
(EtOAc/petrol 1:4) gave the title mesylate as a colourless
Boron trifluoride diethyl etherate (10 lL) was added to
tetra-O-acetyl-2-S-acetyl-2-thio-b-D-glucopyranose24
(220 mg, 0.54 mmol) and PhSH (0.10 mL, 0.76 mmol)
in CH2Cl2 (10 mL) and the solution stirred (rt, 24 h).
Triethylamine (5 mL) was added and subsequent con-
centration of the mixture and flash chromatography
(EtOAc/petrol 1:9) yielded the thioacetate 38 as a col-
ourless oil (217 mg, 88%), [a]D = +1.1 (c 1, CHCl3).
1H NMR (500 MHz): d 1.98, 1.99, 2.06 (3 · s, 9H,
CH3CO), 2.33 (s, CH3COS), 3.55 (dd, J2,3 ꢁ J3,4 11.0,
H2), 3.78 (dd, J4,5 9.3, J5,6 2.4, 5.5, H5), 4.14 (dd,
J6,6 12.0, H6), 4.23 (dd, H6), 4.95 (d, J1,2 10.9, H1),
4.99 (dd, J3,4 9.1, H4), 5.30 (dd, H3), 7.28–7.31, 7.48–
7.50 (2 · m, Ph). 13C NMR (75.5 MHz): d 20.51,
20.54, 20.67 (3 · C, CH3CO), 30.66 (CH3COS), 47.92
(C2), 62.27 (C6), 69.38, 72.22, 75.56 (C3,4,5), 86.36
(C1), 128.14, 128.87, 132.18, 132.75 (Ph), 169.45,
169.96, 170.53 (3 · C, C@O), 192.82 (SC@O). HR-MS
(FAB) m/z 457.0969 [C20H25O8S2 (M+H)+ requires
457.0990].
1
oil (1.7 g, 93%), [a]D = ꢀ10.9 (c 1, CHCl3). H NMR
(500 MHz): d 2.03, 2.06, 2.11 (3 · s, 9H, CH3), 3.03 (s,
CH3SO2), 3.81 (ddd, J4,5 10.1, J5,6 3.0, 5.0, H5), 4.31
(dd, J6,6 11.5, H6), 4.36 (dd, H6), 4.79 (d, J3,4 10.1,
H1), 5.01–5.04 (m, H2,4), 5.27 (dd, J2,3 9.4, J3,4 9.7,
H3), 7.27–7.32, 7.47–7.49 (2 · m, Ph). 13C NMR
(125.7 MHz): d 20.46, 20.62 (CH3), 37.67 (CH3SO2),
66.88 (C6), 67.95, 69.74, 73.60, 75.46 (C2,3,4,5), 85.76
(C1), 128.47, 129.06, 131.31, 132.86 (Ph), 169.15,
169.41, 169.99 (3 · C, C@O). HR-MS (FAB) m/z
477.0862 [C19H25O10S2 (M+H)+ requires 477.0899].
(ii) Phenyl 2,3,4-tri-O-acetyl-6-S-acetyl-1,6-dithio-b-D-
glucoside 37: Potassium thioacetate (800 mg, 7.0 mmol)
was added to the above mesylate (1.6 g, 3.4 mmol) in
DMF (15 mL) and the solution stirred (50 ꢁC, 18 h).
Concentration of the mixture, followed by a standard
work-up (EtOAc) and flash chromatography (EtOAc/
petrol 1:4), gave the thioacetate 37 as a colourless oil
(1.4 g, 91%), [a]D = ꢀ6.0 (c 1, CHCl3). Found: C, 52.4;
3.19. Attempted synthesis of the thioacetate 43
(i) Methyl (20S,30S)-2-O-acetyl-6-O-benzyl-3,4-O-(20,30-
dimethoxybutane-20,30-diyl)-a-D-mannoside 45: Bis(tri-
butyltin) oxide (4.8 mL, 9.3 mmol) was added to methyl
(20S,30S)-3,4-O-(20,30-dimethoxybutane-20,30-diyl)-a-D-
mannoside25 (2.4 g, 7.8 mmol) in PhMe (150 mL) and
the solution heated at reflux to azeotropically remove
H2O (24 h). Benzyl bromide (1.30 mL, 10.9 mmol) was
then added and the solution refluxed (6 h). Concentra-
tion of the mixture and flash chromatography
(EtOAc/petrol 1:4) gave alcohol 44 (2.1 g, 74%) as an
oil. A small portion in pyridine (5 mL) was treated with
Ac2O (5 mL) and the solution stirred (rt, 3 h). The mix-
ture was quenched with MeOH (5 mL) and subsequent
1
H, 5.6. C20H24O8S2 requires C, 52.5; H, 5.5. H NMR
(300 MHz): d 1.98, 2.06, 2.09 (3 · s, 9H, CH3CO), 2.35
(s, CH3COS), 3.09 (dd, J5,6 6.8, J6,6 14.4, H6), 3.25
(dd, J5,6 3.0, H6), 3.64 (ddd, J4,5 9.8, H5), 4.65 (d, J1,2
10.0, H1), 4.89–4.95 (m, H2,4), 5.17 (dd, J2,3 9.3, J3,4
9.5, H3), 7.31–7.35, 7.46–7.49 (2 · m, Ph). 13C NMR
(75.5 MHz): d 20.63, 20.69 (CH3CO), 30.19 (C6), 30.37
(CH3COS), 69.85, 70.19, 73.83, 76.91 (C2,3,4,5), 85.46
(C1), 128.41, 128.89, 131.41, 133.27 (Ph), 169.24,
169.70, 170.15 (3 · C, C@O), 194.66 (SC@O). HR-MS
(FAB) m/z 457.0989 [C20H25O8S2 (M+H)+ requires
457.0990].
concentration, followed by
(EtOAc) and flash chromatography (EtOAc/petrol
a
standard work-up

334
R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
1:9), to furnish acetate 45 as
a
colourless oil,
7.30, 7.31–7.34 (2 · m, Ph). 13C NMR (150.8 MHz): d
20.60, 20.63 (2 · C, CH3CO), 30.33 (CH3COS), 46.42
(C2), 55.51 (OCH3), 68.42 (C6), 68.83, 70.18, 70.23
(C3,4,5), 73.54 (CH2Ph), 99.41 (C1), 127.71, 127.87,
128.35, 137.68 (Ph), 169.55, 170.30 (2 · C, C@O),
193.62 (SC@O). HR-MS (FAB) m/z 427.1408
[C20H27O8S (MꢀH)+ requires 427.1426].
[a]D = +106 (c 1, CHCl3). 1H NMR (500 MHz): d
1.24, 1.26 (2 · s, 6H, CH3), 2.13 (s, CH3CO), 3.17,
3.25, 3.37 (3 · s, 9H, OCH3), 3.75 (m, 2H, H6), 3.89
(ddd, J4,5 9.9, J5,6 2.7, 3.7, H5), 4.06 (dd, J3,4 10.2,
H4), 4.13 (dd, J2,3 3.3, H3), 4.57, 4.65 (AB, J 12.0,
CH2Ph), 4.73 (d, J1,2 1.5, H1), 5.03 (dd, H2), 7.24–
7.28, 7.30–7.35 (2 · m, Ph). 13C NMR (125.7 MHz):
d 17.61, 17.74 (2 · C, CH3), 21.12 (CH3CO), 47.78,
47.99, 54.89 (3 · C, OCH3), 63.45, 66.04, 70.18, 70.54
(C2,3,4,5), 68.43 (C6), 73.41 (CH2Ph), 98.93 (C1),
99.72, 100.14 (C20,30), 127.40, 128.19, 138.30 (Ph),
170.65 (C@O). HR-MS (FAB) m/z 441.2120
[C22H33O9 (M+H)+ requires 441.2124].
(v) Methyl 3,4,6-tri-O-acetyl-2-S-acetyl-2-thio-a-D-gluco-
side 48: Concd H2SO4 (one drop) was added to the tri-
acetate 47 (550 mg) in Ac2O (10 mL) at 0 ꢁC and the
mixture allowed to warm to room temperature
(20 min). The mixture was poured onto ice/water and
standard work-up (CH2Cl2) and flash chromatography
(EtOAc/petrol 1:4) gave the tetraacetate 48 as a colour-
less oil (430 mg, 73%). The 1H NMR spectrum was con-
sistent with that reported.26
(ii) Methyl (20S,30S)-6-O-benzyl-3,4-O-(20,30-dimeth-
oxybutane-20,30-diyl)-2-O-trifluoromethanesulfonyl-a-D-
mannoside:
Trifluoromethanesulfonic
anhydride
(0.76 mL, 4.5 mmol) was added to alcohol 44 (1.6 g,
4.1 mmol) and pyridine (0.67 mL, 8.2 mmol) in CH2Cl2
at ꢀ30 ꢁC and the solution stirred and allowed to warm
to room temperature (30 min). The mixture was
quenched by the addition of saturated NaHCO3 solu-
tion (5 mL) and a standard work-up (CH2Cl2) to give
a yellow oil, presumably the title triflate (2.2 g), which
was used without purification.
3.20. Synthesis of thioacetate 53
(i) Methyl (20S,30S)-2-O-acetyl-3,4-O-(20,30-dimethoxy-
butane-20,30-diyl)-6-O-(4-nitrobenzyl)-a-D-mannoside 50:
According to the procedure described for 45 but using
4-nitrobenzyl bromide (2.40 g, 10.9 mmol) instead of
benzyl bromide, alcohol 49 (2.4 g, 77%) was obtained
as a colourless oil. A small portion of this was converted
into acetate 50, [a]D = +107 (c 1, CHCl3): 1H NMR
(600 MHz): d 1.24 (s, 6H, CH3), 2.11 (s, CH3CO),
3.17, 3.24, 3.35 (3 · s, 9H, OCH3), 3.79 (m, 2H, H6),
3.91 (ddd, J4,5 10.1, J5,6 3.7, H5), 4.04 (dd, J3,4 10.1,
H4), 4.14 (dd, J2,3 3.4, H3), 4.67, 4.74 (AB, J 13.5,
CH2Ar), 4.71 (d, J1,2 1.4, H1), 5.03 (dd, H2), 7.50,
8.18 (AA0BB0, 4H, Ar). 13C NMR (150.8 MHz): d
17.57, 17.71 (2 · C, CH3), 21.11 (CH3CO), 47.78,
47.99, 54.99 (3 · C, OCH3), 63.41, 65.90, 70.11, 70.42
(C2,3,4,5), 69.09 (C6), 72.08 (CH2Ar), 98.97 (C1),
99.77, 100.14 (C20,30), 123.46, 127.26, 145.99, 147.21
(Ar), 170.47 (C@O). HR-MS (FAB) m/z 484.1822
[C22H30NO11 (MꢀH)+ requires 484.1819].
(iii) Methyl (20S,30S)-2-S-acetyl-6-O-benzyl-3,4-O-(20,30-
dimethoxybutane-20,30-diyl)-2-thio-a-D-glucoside
46:
Potassium thioacetate (1.4 g, 12 mmol) was added to
the above triflate (2.2 g) in DMF (30 mL) and the solu-
tion stirred (40 ꢁC, 4 d). Concentration of the mixture,
followed by a standard work-up (EtOAc) and flash chro-
matography (EtOAc/petrol 1:9), furnished thioacetate 46
as a colourless oil (1.7 g, 88%), [a]D = +186 (c 1, CHCl3).
1H NMR (600 MHz): d 1.25, 1.27 (2 · s, 6H, CH3), 2.34
(s, CH3CO), 3.18, 3.24, 3.34 (3 · s, 9H, OCH3), 3.73 (m,
2H, H6), 3.83 (dd, J3,4 9.2,J4,5 10.3, H4), 3.86 (dd, J1,2
3.3, J2,3 11.6, H2), 3.90 (ddd, J5,6 1.9, 5.1, H5), 3.94
(dd, H3), 4.59 (AB, J 12.1, CH2Ph), 4.78 (d, H1), 7.27–
7.29, 7.31–7.35 (2 · m, Ph). 13C NMR (150.8 MHz): d
17.58, 17.66 (2 · C, CH3), 30.47 (CH3CO), 46.04 (C2),
47.89, 47.94, 55.24 (3 · C, OCH3), 66.36 (C3), 68.09
(C4), 68.19 (C6), 69.46 (C5), 73.52 (CH2Ph), 99.58
(C1), 99.80, 100.14 (C20,30), 127.46, 127.48, 128.25,
138.16 (Ph), 194.35 (SC@O). HR-MS (FAB) m/z
455.1724 [C22H31O8S (MꢀH)+ requires 455.1739].
(ii) Methyl (20S,30S)-3,4-O-(20,30-dimethoxybutane-2 0,30-
diyl)-6-O-(4-nitrobenzyl)-2-O-trifluoromethanesulfonyl-
a-D-mannoside: According to the procedure for alcohol
44, alcohol 49 (1.8 g, 4.0 mmol) was converted into the
title triflate (2.3 g), obtained as a yellow oil, which was
used without purification.
(iii) Methyl (20S,30S)-2-S-acetyl-3,4-O-(20,30-dimetho-
xybutane-20,30-diyl)-6-O-(4-nitrobenzyl)-2-thio-a-D-glu-
coside 51: According to the procedure described for 46
but using the above triflate (2.3 g), the thioacetate 51
(iv) Methyl 3,4-di-O-acetyl-2-S-acetyl-6-O-benzyl-2-thio-
a-D-glucoside 47: Thioacetate 46 (700 mg) in CF3COOH/
H2O (1:19, 5 mL) was stirred (rt, 10 min). Concentration
of the solution left a brown residue that was dissolved in
pyridine (10 mL); Ac2O (5 mL) was added and the solu-
tion stirred (rt, 2 h). The mixture was quenched with
MeOH (5 mL) and subsequent concentration, followed
by a standard work-up (EtOAc) and flash chromatogra-
phy (EtOAc/petrol 1:4), to give the triacetate 47 as a col-
ourless oil (590 mg, 90%), [a]D = +66.9 (c 1, CHCl3). 1H
NMR (600 MHz): d 1.89, 1.97 (2 · s, 6H, CH3CO), 2.31
(s, CH3COS), 3.38 (s, OCH3), 3.53 (dd, J5,6 4.4, J6,6 10.3,
H6), 3.56 (dd, J5,6 3.0, H6), 3.94 (m, H2,5), 4.50, 4.59
(AB, J 12.0, CH2Ph), 4.76 (d, J1,2 3.3, H1), 5.14 (dd,
J2,3 9.2, J3,4 9.7, H3), 5.30 (dd, J4,5 9.4, H4), 7.27–
was obtained as
a colourless oil (1.8 g, 88%),
1
[a]D = +152 (c 1, CHCl3). H NMR (500 MHz): d 1.27
(s, 6H, CH3), 2.33 (s, CH3CO), 3.18, 3.24, 3.34 (3 · s,
9H, OCH3), 3.75 (dd, J5,6 2.0, J6,6 10.9, H6), 3.80 (dd,
J5,6 4.6, H6), 3.84 (dd, J3,4 9.9, J4,5 10.0, H4), 3.86 (dd,
J1,2 3.3, J2,3 9.2, H2), 3.92 (ddd, H5), 3.95 (dd, H3),
4.68, 4.72 (AB, J 13.5, CH2Ar), 4.77 (d, H1), 7.50,
8.19 (AA0BB0, 4H, Ar). 13C NMR (125.7 MHz): d
17.55, 17.62 (2 · C, CH3), 30.46 (CH3CO), 45.96 (C2),
47.84, 47.95, 55.28 (3 · C, OCH3), 66.21 (C3), 68.01
(C4), 68.81 (C6), 69.43 (C5), 72.22 (CH2Ar), 99.62
(C1), 99.86, 100.14 (C20,30), 123.53, 127.32, 145.86,

R. V. Stick, K. A. Stubbs / Tetrahedron: Asymmetry 16 (2005) 321–335
335
147.24 (Ar), 194.38 (C@O). HR-MS (FAB) m/z
References
500.1556 [C22H30NO11S (MꢀH)+ requires 500.1590].
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(iv) Methyl 3,4-di-O-acetyl-2-S-acetyl-6-O-(4-nitrobenz-
yl)-2-thio-a-D-glucoside 52: According to the procedure
described for the preparation of 47 but using 51
(700 mg), triacetate 52 was obtained as a colourless oil
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(v) 1,3,4-Tri-O-acetyl-2-S-acetyl-6-O-(4-nitrobenzyl)-2-
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1
C, 52.4; H, 4.8. H NMR (600 MHz): d 1.94, 1.97, 2.10
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We thank Professor Stephen Withers for a generous gift
of both the glycosynthase and the thioglycoligase (with-
out which this work could not have proceeded) and Dr.
Andrew G. Watts for helpful discussion. K.A.S. would
like to thank The University of Western Australia for
a Hackett postgraduate scholarship.
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¨