1,6-Epithio- and 1,6-Episeleno-β-D-glucopyranose: Useful Adjuncts in the Synthesis of 6-Deoxy-β-D-glucopyranosides

Article abstract of DOI:10.1071/CH99009

Derivatives of 1,6-dideoxy-1,6-epithio- and 1,6-dideoxy-1,6-episeleno-β-D-glucopyranose have been shown to be effective glycosyl donors toward carbohydrate alcohols under the agency of N-iodosuccinimide/trifluoromethanesulfonic acid. Reduction of the inte

Full text of DOI:10.1071/CH99009

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 52, 1999
© CSIRO Australia 1999
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Aust. J. Chem., 1999, 52, 685–693
.
1,6-Epithio- and 1,6-Episeleno- -D-glucopyranose:
Useful Adjuncts in the Synthesis of
6-Deoxy- -D-glucopyranosides
Robert V. Stick,A,B D. Matthew G. Tilbrook A and Spencer J. Williams A
A
Department of Chemistry, The University of Western Australia, Nedlands, W.A. 6907.
Author to whom correspondence should be addressed.
B
Derivatives of 1,6-dideoxy-1,6-epithio- and 1,6-dideoxy-1,6-episeleno- -D-glucopyranose have been
shown to be e ective glycosyl donors toward carbohydrate alcohols under the agency of N -
iodosuccinimide/tri uoromethanesulfonic acid. Reduction of the intermediate disul des and diselenides
a ords 6-deoxy- -D-glucopyranosides. The synthesis of a range of such 60-deoxy disaccharide derivatives
is reported.
Deoxy sugars are widely represented in Nature
and, particularly, in oligosaccharides where they are
frequently present as the terminal sugars necessary
for mediation of recognition processes and tra cking
of molecules within biological systems. Deoxy sugars
such as L-fucose and L-rhamnose are present in bio-
logically active molecules such as the Lea, Leb and
Lex blood group determinants1 and sialyl Lewisx,2
as well as a range of carbohydrate-containing drugs
such as the antibiotic cytovaricin and the antitumour
compound calicheamycin 1. Synthetic approaches to
molecules such as these have been possible only recently
owing to major advances in glycosidic bond-forming
technology.3,4
approach to the synthesis of this molecule centres
on 2-O-acetyl-3,4-anhydro-1,6-dideoxy-1,6-epithio- -D-
galactose (2), a molecule beautifully arranged for the
introduction of an amine (C 4), glycoside formation
(C 1) and deoxygenation (C 6).
We have previously reported on model studies
describing the introduction of nitrogen nucleophiles
at C 4 into a sugar such as (2);6 here, we disclose
full details on the use of 1,6-dideoxy-1,6-epithio and
1,6-dideoxy-1,6-episeleno sugars as glycosyl donors for
the synthesis of 6-deoxy sugars—the general approach
is outlined in Scheme 1.7 At this point, it is worth
noting that Lundt and Skelb k-Pedersen have reported
the synthesis of the crystalline sulfonium salt (3) and
have demonstrated that it has some utility as a glycosyl
donor.8 Our investigations here were aimed at taking
advantage of more recent reagent systems developed
for the activation of thio- and seleno-glycosides.9
Thioglycosides have gained deserved prominence
as reliable glycosyl donors in the preparation of
oligosaccharides.5 Of particular appeal is the stability
of thioglycosides to a broad range of reagents and
conditions, making them ideal starting materials for
the preparation of diversely functionalized glycosyl
donors. One current interest in our laboratory is the
synthesis of -acarbose (1), a putative inhibitor of
enzymes which process -D-glucosidic linkages. One
The 1,6-dideoxy-1,6-epithio sugar (4) was pre-
pared according to known methods.6 Initially, treat-
ment of a mixture of the epithio sugar (4) and
the commercially available alcohol (5) with N -
iodosuccinimide/tri uoromethanesulfonic acid a orded
only the acetate (6), in poor yield. To test the viability
of our glycosylation procedure, the ethylthio D-glucoside
(7) was treated in an identical manner to that above
Manuscript received 21 January 1999
᭧ CSIRO 1999
10.1071/CH99009
0004-9425/99/070685$ 05.00

686
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
with the same alcohol (5). In our hands, the disaccha-
ride (8) and the acetate (6) were formed, each in 32%
yield. Furthermore, the phenylthio D-glucoside (9) was
no more successful as a glycosyl donor, again a ording
both the disaccharide (8) and the acetate (6) in yields of
42% and 32%, respectively. The acetate (6) presumably
arose from acetyl transfer from the donors to the alcohol
(5). Transesteri cation of this sort has previously been
noted with a number of acetylated glycosyl donors,
such as glycosyl bromides10 and thioglycosides.11,12
In the case of the silver tri ate-promoted reaction
of tetra-O-acetyl- -D-galactopyranosyl bromide with
methyl 2,4,6-tri-O-benzoyl- -D-galactoside, a labelled
donor was used to show that the acetyl group
transferred to the acceptor originated from O 2 of
the donor.10 Despite such well established literature
precendents, the observed transesteri cation never-
theless contrasts with the work of Fraser-Reid and
coworkers who were able to e ect glycosylation of the
alcohol (5) with the acetylated donor (9) under the
agency of N -iodosuccinimide/tri uoromethanesulfonic
acid to a ord (8) in 89% yield.13 In both cases, our
yields of the disaccharide (8) were substantially less
than that quoted by Fraser-Reid and coworkers and
the reactions were complicated by the formation of
the acetate (6).
It is well known that benzoyl groups at O 2 direct 1,2-
trans-glycosylation and, moreover, are less susceptible
to transfer to an acceptor alcohol.14 In addition, we were
encouraged by our recent, successful work that used
benzoylated thio-, seleno- and telluro- -D-glucosides
as glycosyl donors.15 Therefore, the tribenzoate (10)

1,6-Epithio- and 1,6-Episeleno- -D-glucopyranose
687
was prepared by treatment of the triacetate (4) with
sodium methoxide in methanol and, subsequently,
benzoyl chloride in pyridine.
compounds may have resulted from debenzoylation
of the substrates, caused by basic residues present
in the Raney nickel, under the prolonged treatment
required for the desulfurization of the apparently unre-
active disul des. Alternatively, in the case of the
disul des (19), (20) and (22), some reductive deben-
zylation may have occurred. In a more successful
approach, the disul des (11) and (18) were deacylated
by treatment with sodium methoxide in methanol and
then acetylated to give the acetates (24) and (25),
respectively. These compounds, upon treatment with
Raney nickel in ethanol, rapidly and reliably gave
the 6-deoxy- -D-glucosides (26) and (27) (Table 2;
method B).
Gratifyingly, treatment of a mixture of the tribenzoate
(10) and the alcohol (5) with N -iodosuccinimide/tri-
uoromethanesulfonic acid a orded the disul de (11)
in an excellent yield. The identity of the disul de (11)
was supported by high-resolution mass spectrometry
and by the presence of a signal at 40 63 in the 13C
n.m.r. spectrum, assigned to C 60. A rationale for the
formation of the disul de is presented in Scheme 2.
Table 2. Preparation of the various
6-deoxy- -D-glucopyranosides
Method A: Raney nickel, EtOH. Method B: (i) NaOMe, MeOH;
(ii) Ac2O, pyridine; (iii) Raney nickel, EtOH. Method C: (i)
NaOMe, MeOH; (ii) Na, NH3, tetrahydrofuran; (iii) Ac2O,
pyridine; (iv) Raney nickel
Method
used
Disul de
treated
Thioacetate/
disul de
6-Deoxy-
-D-glucoside
B
B
C
C
A
C
(11)
(18)
(19)
(20)
(21)
(22)
(24) 81%
(25) 77%
(29) 60%
(30) 57%
— —
(31) 59%
(26) 69%
(27) 75%
(27) 67%
(32) 85%
(23) 84%
(33) 85%
To explore the generality of this reaction the alco-
hols (12),16 (13),17 (14),18 (15),19 (16)20 and (17)
were treated with the tribenzoate (10) in a manner
similar to that above—the results of these reactions
are presented in Table 1. Some aspects of these
results deserve comment. Firstly, the only alcohol
shown to be unreactive to the donor (10) was the
di-O-isopropylidene- -D-glucofuranose (17), a notori-
ously unreactive acceptor. Secondly, the yield of these
glycosylations was dependent upon the scale of the
reaction, with the best results being obtained on a
larger scale—presumably, the variation in yield was
due to a constant amount of adventitious water, the
e ect of which diminished with increasing scale.
Buoyed by these results, we converted the disul de
(22) into the acetate (28), and treated the acetate
with Raney nickel in ethanol; however, again and
disappointingly, a slow conversion into the deoxy sugar
and a poor mass return was evident. Therefore, the
remaining three compounds (19), (20) and (22) were
debenzoylated, then treated with sodium in liquid
ammonia and acetylated to a ord the thioacetates
(29), (30) and (31), respectively. Upon treatment with
Raney nickel in ethanol, all three compounds cleanly
a orded the various 6-deoxy- -D-glucosides in good
yield (Table 2; method C).
Table 1. Glycosylation reactions of the donors (4) and (10)
with a range of carbohydrate alcohols
The preparation of hepta-O-acetyl-60-deoxy- -cello-
biose (33) by acetolysis of methyl hepta-O-acetyl-60-
deoxy- -cellobioside has been described by Jezo and
Zemek.21 However, the melting point and optical
rotation reported for their material {m.p. 185–186
(CHCl3/petrol), [ ]D +25 3 (CHCl3)} do not agree
with the values obtained here {m.p. 225 5–226 (EtOH),
[ ]D +57 7 (CHCl3)}. On the basis of a doublet at
6 22 (J 3 8 Hz) in the 1H n.m.r. spectrum being
assigned to H 1, the compound here was assigned the
-con guration. Jezo and Zemek fail to report any
n.m.r. data for their material and it would appear
likely that they, in fact, isolated the -anomer, hepta-
O-acetyl-60-deoxy- -cellobiose.
Reactants
Disul de
Reactants
Disul de
(4)+(5)
(10)+(5)
(12)
—
0%A
(10)+(14)
(15)
(16)
(20) 69%
(21) 63%
(22) 82%
(11) 76%
(18) 92%
(19) 51%
(13)
(17)
—
0%
A
Only the acetylated acceptor (6) was isolated.
The reductive desulfurization of these compounds
was the next step to be investigated. Raney nickel is
well known for its selective ability to remove sulfur
from organosulfur compounds; however, treatment of
the disul des (11) and (18)–(22) with Raney nickel in
ethanol was disappointing. Only the disul de (21) was
readily reduced by Raney nickel, a ording the dideoxy
sugar (23) in good yield (Table 2; method A). Chro-
matographic evidence (t.l.c.) otherwise was indicative
of the formation of highly polar compounds—such
The results presented above for the desulfurization
of the various disul des are di cult to rationalize. In
all cases, the Raney nickel was used within 1 month
of preparation and thus retained high activity. The

688
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
Epithio and Episeleno Sugars (10) and (35)
disul de (21) possesses both benzoyl and benzyl groups,
yet was converted rapidly and in high yield into the
dideoxy D-glucoside (23) upon treatment with Raney
nickel. The remaining compounds were recalcitrant
and required quite extensive manipulation to enable
desulfurization.
The mixed and somewhat disappointing results in the
glycosylation studies with the 1,6-dideoxy-1,6-epithio
sugars (4) and (10) prompted investigations into glycosy-
lations with 1,6-dideoxy-1,6-episeleno sugars. In a fash-
ion similar to that of before, a solution of tri-O-acetyl-
1,6-dideoxy-1,6-episeleno- -D-glucopyranose (34)6 and
the di-O-isopropylidene- -D-galactose (5) was treated
with N -iodosuccinimide/tri uoromethanesulfonic acid,
to a ord a mixture from which only the acetate (6)
could be isolated. As before, protecting group exchange
from acetyl to benzoyl a orded the tribenzoate (35).
The tribenzoate (35) was treated with the alcohol (16)
under the now standard conditions to a ord, in an
acceptable yield (54%), the diselenide (36).
2,3,4-Tri-O-benzoyl-1,6-dideoxy-1,6-epithio-
-D-glucose (10)
2,3,4-Tri-O-acetyl-1,6-dideoxy-1,6-epithio- -D-glucose (4)6
(2 5 g, 8 2 mmol) was suspended in dry MeOH (25 ml) at
room temperature and a small piece of sodium metal added.
The mixture was stirred for 90 min and then resin (Dowex 50,
H+) was added until the solution became neutral. The mixture
was ltered and evaporated under reduced pressure, then water
(20 ml) was added. The water was evaporated and the residue
freeze-dried to give a white powder. The solid was suspended
in dry CH2Cl2 (10 ml) and dry pyridine (2 5 ml) and the
suspension was treated with benzoyl chloride (4 0 ml, 4 8 g,
35 mmol) at 0 for 1 h and then stirred at room temperature
for 4 h. T.l.c. analysis indicated complete conversion into a
lower polarity compound. Water (1 ml) was added and the
mixture was stirred for 20 min. The mixture was treated to
the usual workup (CH2Cl2) to give an oil. The oil was taken
up in ether and crystallization ensued upon the addition of
petrol, a ording the tribenzoate (10) as white cubes (3 60 g,
89%), m.p. 170–173 (Et2O/petrol), [ ]D 31 2 (Found: C,
66 3; H, 4 7.
n.m.r. (300 MHz)
3 42, d, J5,6
C
27H22O7S requires C, 66 1; H, 4 5%). 1H
3 31, dd, J5,6 6 7, J6,6 10 2 Hz, H 6;
0 Hz, H 6; 5 03–5 10, m, H 4,5; 5 16, m,
The carbon–selenium bond is considerably weaker
than the carbon–sulfur bond, and, consequently, allows
for milder reagents to e ect its reduction. Thus, the
diselenide (36) was treated with tributylstannane and
H 2; 5 57, m, H 3; 5 77, br s, H 1; 7 38–8 15, m, 15H, Ph.
13C n.m.r. (75 5 MHz)
53 94, C 6; 68 91, 71 66, 73 44,
78 92, 81 69, C 1,2,3,4,5; 128 42–129 98, 133 50, 133 57, Ph;
164 95, 165 34, 165 53, 3C, CO.
,
0-azobisisobutyronitrile at re ux in toluene, result-
ing in the rapid and clean conversion into the 6-deoxy
sugar (37) in an excellent yield (94%).
2,3,4-Tri-O-benzoyl-1,6-dideoxy-1,6-episeleno-
-D-glucose (35)
2,3,4-Tri-O -acetyl-1,6-dideoxy-1,6-episeleno- -D-glucose
(34)6 (6 58 g, 18 8 mmol) was treated in the same man-
ner as for the triacetate (4), yielding the tribenzoate (35) as
colourless needles (7 09 g, 70%) in two crops, m.p. 175–176
Table 3. Glycosylation reactions of the donors (34) and (35)
with a range of carbohydrate alcohols
Reactants
used
6-Deoxy-
-D-glucoside
Reactants
used
6-Deoxy-
-D-glucoside
(CH2Cl2/petrol), [ ]D
27H22O7Se requires C, 60 3; H, 4 1%). 1H n.m.r. (300 MHz)
3 11–3 36, m, H 6; 3 61, br d, J5,6 9 4 Hz, H 6; 5 09, dd,
47 0 (Found: C, 60 1; H, 4 0.
(34)+(5)
(35)+(5)
—
0%A
(38) 73%
(35)+(14)
(16)
(17)
(39) 55%
(37) 64%
C
J3,4 4 9, J4,5 1 9 Hz, H 4; 5 11, br d, H 5; 5 31, d, J2,3 3 7
Hz, H 2; 5 69, dd, H 3; 6 11, br s, H 1; 7 37–8 10, m, 15H,
Ph. 13C n.m.r. (75 5 MHz) 30 18, C 6; 68 89, 72 63, 75 17,
77 07, 80 70, C 1,2,3,4,5; 128 45–129 91, 133 43, Ph; 165 07,
165 47, 165 61, 3C, CO.
—
0%
A
Only the acetylated acceptor (6) was isolated.
The reduced yield of the glycosylation to form the
diselenide (36), compared to the analogous disul de
(22), and the formation of very polar compounds (as
shown by t.l.c.) believed to contain selenium prompted
an approach involving the direct reduction of the
reaction mixture after workup. Now, the tribenzoate
(35) was treated with the alcohols (5), (14) and (16)
as above to a ord a mixture which, after aqueous
workup, was treated directly with tributylstannane
to provide the 6-deoxy- -D-glucosides (38), (39) and
(37), respectively, in excellent overall yields (Table 3).
Unfortunately, but not entirely surprisingly, the treat-
ment of a solution of the donor (35) and the alcohol
(17) with N -iodosuccinimide/tri uoromethanesulfonic
acid a orded no products of glycosylation.
Glycosylations with the Epithio and Episeleno Sugars
Representative Procedures
(a) A solution of N -iodosuccinimide (63 mg, 0 28 mmol)
and tri uoromethanesulfonic acid (2–10 l, 0 02–0 1 mmol) in
dry Et2O/1,2-dichloroethane (1 : 1, 4 ml) at 0 was added to a
solution of the donors (4), (7), (10), (34) or (35) (0 24 mmol)
and acceptor (0 20 mmol) in dry 1,2-dichloroethane (2 ml)
at 0 . After completion of the reaction (t.l.c.), the solution
was quenched with saturated aqueous NaHCO3 (1 ml) and
aqueous Na2S2O3 (10%, 1 ml), the organic layer was separated,
dried, the solvent evaporated and the residue puri ed by ash
chromatography to give the various products.
(b) In the case of the 1,6-episeleno donor (35), after
glycosylation and workup as in (a), the crude residue was
dissolved in dry toluene (4 ml) and treated with Bu3SnH
(160 l, 0 60 mmol) and
,
0-azobisisobutyronitrile (1 mg) at
Experimental
re ux. After completion of the reaction (t.l.c.), the solvent
was evaporated and the residue partitioned between MeCN
and petrol. The MeCN layer was separated and evaporated
and the residue subjected to ash chromatography to give the
various 6-deoxy- -D-glucopyranosides.
General experimental procedures have been given
previously.22
Raney nickel (W4) was prepared according to the procedure
of Augustine and used within 1 month of preparation.23

1,6-Epithio- and 1,6-Episeleno- -D-glucopyranose
689
6-O-Acetyl-1,2:3,4-di-O-isopropylidene- -D-galactose (6)
and 1,2:3,4-Di-O-isopropylidene-6-O-(tetra-O-acetyl- -D-
glucosyl)- -D-galactose (8)
2 4 Hz, H 2; 4 46, dd, H 3; 4 90, d, J1 ,2
dd, J3 ,4 9 6, J4 ,5
J2 ,3
9 6 Hz, H 20; 5 79, dd, H 30; 7 22–7 97, m, 15H, Ph.
13C n.m.r. (125 8 MHz)
24 42, 24 83, 25 66, 25 97, 4C,
0
0
7 9 Hz, H 10; 5 33,
0
0
0
0
9 6 Hz, H 40; 5 41, d, H 1; 5 44, dd,
0
0
(a) Ethyl tetra-O-acetyl-1-thio- -D-glucopyranoside (7)24,25
(470 mg, 1 20 mmol) and 1,2:3,4-di-O-isopropylidene- -D-
galactose (5) (2 8 ml of 0 35 M in 1,2-dichloroethane, 1 0
mmol) were treated as described in procedure (a) above to
give, after ash chromatography (25–40% EtOAc/petrol), the
acetate (6) as a syrup (109 mg, 32%). This material gave
an identical 1H n.m.r. (300 MHz) spectrum to the material
prepared as outlined below.
Next to elute was the disaccharide (8) as a foam (186 mg,
32%). This material gave an identical 1H n.m.r. (300 MHz)
spectrum to the material prepared as outlined below.
(b) Phenyl tetra-O -acetyl-1-thio- -D -glucopyranoside
(9)24,25 (440 mg, 1 00 mmol), 1,2:3,4-di-O-isopropylidene- -
D-galactose (5) (3 1 ml of 0 362 M in CH2Cl2, 1 10 mmol),
N -iodosuccinimide (270 mg, 1 2 mmol) and powdered molec-
ular sieves (4 A, 1 g) were suspended in dry CH2Cl2 (3 ml)
Me; 40 63, C 60; 67 43, C 5; 68 32, C 6; 70 33, C 2; 70 53,
C 3; 70 95, C 4; 71 80, C 20; 72 05, C 40; 72 85, C 30; 72 96,
C 50; 96 12, C 1; 101 22, C 10; 108 41, 109 33, 2C, CMe2;
128 13–129 93, 132 95–133 51, Ph; 165 06, 165 34, 165 66,
3C, CO. High-resolution mass spectrum (f.a.b.) m/z 1498 01
[C78H82O26S2 (M+ ) requires 1498 45].
Dimethyl 6,6 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)]bis(2,3,4-tri-O-acetyl- -D-glucoside)
(18)
The tribenzoate (10) (500 mg, 1 02 mmol) and methyl
2,3,4-tri-O-acetyl- -D-glucoside (12)16 (272 mg, 0 849 mmol)
were treated as described in procedure (a) above to give, after
ash chromatography (40–45% EtOAc/petrol), the disul de
(18) as a glass (631 mg, 92%), [ ]D +74 3 (Found: C, 59 1;
H, 5 3. C80H82O32S2 requires C, 59 3; H, 5 1%). 1H n.m.r.
(300 MHz) 1 93, 1 97, 2 00, 3s, 9H, Ac; 2 88–2 93, m, 2H,
H 60; 2 96, s, OMe; 3 60, dd, J5,6 7 0, J6,6 10 9 Hz, H 6;
3 87–4 00, m, H 5,6,50; 4 66, d, J1,2 3 6 Hz, H 1; 4 71, dd,
at
5
under N2. Tri uoromethanesulfonic acid (200 l of
0 15 M in CH2Cl2, 0 03 mmol) was added, whereupon the
suspension turned deep purple over 3 min. T.l.c. indicated the
disappearance of the starting material, so saturated aqueous
sodium bicarbonate solution (1 ml) and aqueous sodium thio-
sulfate solution (1 ml of 0 5 M) were added. The mixture was
ltered, diluted with CH2Cl2 and the organic phase washed
with saturated aqueous NaHCO3, aqueous Na2S2O3 and brine,
then dried. The solvent was evaporated and the residue
puri ed by ash chromatography (25–40% EtOAc/petrol) to
give the acetate (6) as a white, crystalline solid (96 mg, 32%).
This material crystallized as white needles, m.p. 109–110
(EtOH/H2O; lit.26 109–110 ), [ ]D 47 2 (lit.26 47 2 ).
Next to elute was the disaccharide (8) as a white, crystalline
solid (245 mg, 42%). This material crystallized as white
needles, m.p. 140–141 (EtOH; lit.14 140–141 ), [ ]D 58 2
(lit.14 56 ).
J2,3 10 0 Hz, H 2; 4 80, d, J1 ,2
J4,5 9 7 Hz, H 4; 5 33, dd, J3 ,4
5 38, dd, H 3; 5 45, dd, J2 ,3
7 9 Hz, H 20; 5 79, dd, H 30;
0
0
7 9 Hz, H 10; 4 83, t, J3,4
9 6, J4 ,5
9 6 Hz, H 40;
0
0
0
0
0
0
7 23–7 55, 7 77–7 94, 2m, 15H, Ph. 13C n.m.r. (75 5 MHz)
20 55, COMe; 40 83, C 60; 54 74, OMe; 68 19, 69 02, 69 98,
70 74, 71 76, 71 98, 72 55, 73 16, C 2,3,4,5,20,30,40,50; 68 47,
C 6; 96 00, C 1; 101 24, C 10; 128 18–129 70, 133 07, 133 55,
Ph; 164 97, 165 28, 165 60, 3C, COPh; 169 65, 169 90,
169 96, 3C, COMe. High-resolution mass spectrum (f.a.b.)
m/z 1617 9960 [C80H82O32S2 (M+ ) requires 1618 4229].
Dimethyl 6,6 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)]bis(2,3,4-tri-O-benzyl- -D-glucoside)
(19)
6-O-Acetyl-1,2:3,4-di-O-isopropylidene- -D-galactose (6)
The tribenzoate (10) (127 mg, 257 mol) and methyl 2,3,4-
tri-O-benzyl- -D-glucoside (13)17 (100 mg, 216 mol) were
treated as described in procedure (a) above to give, after ash
chromatography (5% EtOAc/toluene), the disul de (19) as a
syrup (105 mg, 51%), [ ]D +51 8 (Found: C, 69 2; H, 5 6.
(a) The triacetate (4) (168 mg, 554 mol) and 1,2:3,4-di-
O-isopropylidene- -D-galactose (5) (120 mg, 462 mol) were
treated as described in procedure (a) above to give, after
ash chromatography (30–50% EtOAc/petrol), the unreacted
triacetate (4) (12 mg).
Next to elute was the acetate (6) as a syrup (50 mg,
35%). This material gave an identical 1H n.m.r. (300 MHz)
spectrum to the material prepared as outlined above. Finally,
also recovered was some unreacted alcohol (5) (9 mg).
(b) The triacetate (34) (143 mg, 407 mol) and 1,2:3,4-
di-O-isopropylidene- -D-galactose (5) (88 mg, 340 mol) were
treated as described in procedure (a) above to give, after ash
chromatography (25–50% EtOAc/petrol), the acetate (6) as
a syrup (13 mg, 20% based on the alcohol consumed). This
material gave an identical 1H n.m.r. (300 MHz) spectrum to
the material prepared as outlined above.
C
110H106O26S2 requires C, 69 2; H, 5 6%). 1H n.m.r. (500
MHz) 2 83, dd, J5 ,6 2 8, J6 ,6
14 2 Hz, H 60; 2 92, dd,
J5 ,6 J4,5 9 4 Hz,
8 8 Hz, H 60; 3 24, s, Me; 3 41, t, J3,4
0
0
0
0
0
0
H 4; 3 45, dd, J1,2 3 5, J2,3 9 6 Hz, H 2; 3 68–3 72, m, H 5;
3 76, dd, J5,6 3 8, J6,6 10 3 Hz, H 6; 3 89, dd, H 3; 3 91, dd,
J4 ,5
6H, CH2Ph; 4 53, d, H 1; 4 69, d, J1 ,2
7 8 Hz, H 10; 5 32,
dd, J3 ,4
0
9 6 Hz, H 40; 5 51, dd, J2 ,3 9 8 Hz, H 20; 5 79,
0
0
9 3 Hz, H 50; 4 18, dd, J5,6 1 4 Hz, H 6; 4 25–4 90, m,
0
0
0
0
0
dd, H 30; 7 00–7 53, 7 77, 7 88, 2m, Ph. 13C n.m.r. (125 8
MHz) 40 58, C 60; 55 05, Me; 68 08, C 6; 69 31, C 5; 71 78,
C 20; 71 99, C 40; 72 65, C 30; 73 16, C 50; 73 38, 74 61, 75 50,
3C, CH2Ph; 77 14, C 4; 79 69, C 2; 81 86, C 3; 99 97, C 1;
100 88, C 10; 127 42–129 87, 133 11–133 64, 138 15, 138 78,
Ph; 164 86, 165 34, 165 73, 3C, CO. Mass spectrum (f.a.b.)
m/z 1906 (very weak) [C110H106O26S2 (M+ ) requires 1906].
Next to elute was some unreacted alcohol (5) (23 mg).
6,6 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-deoxy- -D-
glucosyl)]bis(1,2:3,4-di-O-isopropylidene- -D-galactose)
(11)
Dimethyl 3,3 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)]bis(2,4,6-tri-O-benzyl- -D-glucoside)
(20)
The tribenzoate (10) (319 mg, 651 mol) and 1,2:3,4-di-
O-isopropylidene- -D-galactose (5) (141 mg, 542 mol) were
treated as described in procedure (a) above to give, after ash
chromatography (5–15% EtOAc/toluene), the disul de (11) as
a syrup (311 mg, 76%), [ ]D +14 2 (Found: C, 62 1; H, 5 8;
S, 4 4. C78H82O26S2 requires C, 62 5; H, 5 5; S, 4 3%). 1H
n.m.r. (500 MHz) 1 19, 1 26, 1 42, 3s, 12H, Me; 2 88–2 99,
2H, m, H 60; 3 82, dd, J5,6 6 9, J6,6 10 9 Hz, H 6; 3 87,
ddd, J4,5 1 8, J5,6 4 4 Hz, H 5; 3 97–4 00, m, H 50; 4 01,
dd, H 6; 4 15, dd, J3,4 7 9 Hz, H 4; 4 20, dd, J1,2 5 0, J2,3
The tribenzoate (10) (89 mg, 181 mol) and methyl 2,4,6-
tri-O-benzyl- -D-glucoside (14) (70 mg, 151 mol) were treated
as described in procedure (a) above to give, after ash chro-
matography (5% EtOAc/toluene), the disul de (20) as a clear
syrup (99 mg, 69%), [ ]D +13 8 (Found: C, 69 4; H, 5 7.
C
110H106O26S2 requires C, 69 2; H, 5 6%). 1H n.m.r. (300
MHz) 2 57, dd, J5 ,6 7 6, J6 ,6
14 1 Hz, H 60; 2 74, dd,
J5 ,6
3 1 Hz, H 60; 3 24, s, Me; 3 30, dd, J1,2 3 5, J2,3 9 6
0
0
0
0
0
0

690
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
0 0
3 2 Hz, H 60; 3 18–3 24, m, H 5; 3 43–3 71, m, 5H,
dd, J5 ,6
Hz, H 2; 3 54–3 75, m, 4H, H 4,5,6; 3 95, ddd, J4 ,5
H 50; 4 07–5 12, m, 6H, CH2Ph; 4 25, d, H 1; 4 34, t, J2,3
J3,4 9 3 Hz, H 3; 5 33, dd, J3 ,4
5 39, d, J1 ,2
5 85, dd, H 30; 7 00–8 01, m, Ph. 13C n.m.r. (75 5 MHz)
40 50, C 60; 54 92, Me; 68 49, C 6; 69 37, 72 05, 72 58, 73 00,
75 24, 79 18, 80 79, 8C, C 2,3,4,5,20,30,40,50; 73 41, 73 77,
74 27, 3C, CH2Ph; 97 73, C 1; 100 59, C 10; 127 24–129 77,
133 14, 133 31, 137 90–138 86, Ph; 165 13, 165 24, 165 70,
3C, CO. High-resolution mass spectrum (f.a.b.) m/z 1907 40
[C110H107O26S2 (M+H)+ requires 1906 64].
0
0
10 1 Hz,
H 2,3,6,50; 4 08, t, J3,4
8H, CH
J4,5 9 2 Hz, H 4; 4 38–5 02, m,
0 0
2Ph; 4 41, d, J1,2 7 2 Hz, H 1; 4 80, d, J1 ,2 7 9
J4 ,5 9 6 Hz, H 40;
9 9 Hz, H 20;
0
0
0
0
0
0
7 9 Hz, H 10; 5 54, dd, J2 ,3
0
0
Hz, H 10; 5 18, dd, J3 ,4
J2 ,3
0 0
0
0
9 6, J4 ,5
0
0
9 6 Hz, H 40; 5 37, dd,
9 8 Hz, H 20; 5 58, dd, H 30; 7 07–8 11, m, Ph. 13C
n.m.r. (75 5 MHz) 31 42, C 60; 67 66, 70 89, 73 63, 74 80,
74 90, 5C, C 6, CH2Ph; 72 55, 72 98, 74 14, 74 40, 76 62,
81 69, 82 37, 8C, C 2,3,4,5,20,30,40,50; 99 73, C 10; 102 46, C 1;
127 06–139 45, Ph; 164 78, 165 23, 165 62, 3C, CO.
Benzyl 2,3,6-Tri-O-benzyl-4-O-(2,3,4-tri-O-benzoyl-6-deoxy-
-D-glucosyl)- -D-glucoside (37)
Dimethyl 4,4 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)]bis(2,3-di-O-benzyl-6-deoxy- -D-
glucoside) (21)
(a) A solution of the diselenide (36) (32 mg, 15 mol)
in dry toluene (3 ml) was treated with Bu3SnH (25 l, 26
mg, 89 mol) and
,
0-azobisisobutyronitrite (2 mg) at re ux
The tribenzoate (10) (165 mg, 335 mol) and methyl 2,3-
di-O-benzyl-6-deoxy- -D-glucopyranoside (15)19 (100 mg, 279
mol) were treated as described in procedure (a) above to give,
after ash chromatography (5% EtOAc/toluene), the disul de
(21) as a clear oil (149 mg, 63%) which crystallized as akes,
m.p. 116–119 (CH2Cl2/petrol), [ ]D +60 5 (Found: C, 68 2;
H, 5 5. C96H94O24S2 requires C, 68 1; H, 5 5%). 1H n.m.r.
under N2 for 3 h. The solvent was evaporated and the residue
dissolved in MeCN and the solution washed (5 ) with petrol.
The solvent was evaporated from the acetonitrile layer and
the residue puri ed by passage through a short plug of silica
(0–10% EtOAc/toluene) to give the deoxy sugar (37) as a clear
oil (28 mg, 94%). This oil crystallized as chunky crystals, m.p.
225 5–226 0 (Et2O/petrol), [ ]D 17 6 (Found: C, 73 2;
(500 MHz) 1 22, d, J5,6 6 2 Hz, 3H, H 6; 2 46, dd, J5 ,6
0
0
H, 6 1.
(300 MHz) 1 19, d, J5 ,6
H 5; 3 47–3 62, m, H 2,3,6,50; 3 67, dd, J5,6 3 7, J6,6 11 0
Hz, H 6; 4 04, t, J3,4 J4,5 9 2 Hz, H 4; 4 37–5 05, m, 8H,
CH2Ph; 4 41, d, J1,2 7 6 Hz, H 1; 4 92, d, J1 ,2 8 0 Hz,
H 10; 5 25, t, J3 ,4 9 6 Hz, H 40; 5 44, dd, J2 ,3
J4 ,5
C
61H58O13 requires C, 73 3; H, 5 9%). 1H n.m.r.
6 2 Hz, 3H, H 60; 3 18–3 25, m,
7 5, J6 ,6
0
0
14 2 Hz, H 60; 2 59, dd, J5 ,6 3 1 Hz, H 60; 3 29,
0
0
0
0
dq, J4,5 9 4 Hz, H 5; 3 42, dd, J1,2 7 9, J2,3 9 1 Hz, H 2;
3 51, s, OMe; 3 52, dd, J3,4 9 3 Hz, H 4; 3 63, dd, H 3;
3 81, ddd, J4 ,5
4 69–5 06, m, 4H, CH2Ph; 5 03, d, H 1; 5 29, dd, J3 ,4
J4 ,5
9 6 Hz, H 40; 5 48, dd, J2 ,3 9 9 Hz, H 20; 5 77, dd,
0
0
9 6 Hz, H 50; 4 25, d, J1 ,2
0
0
7 8 Hz, H 10;
0
0
0
0
0
0
0
0
0
0
9 8 Hz, H 20; 5 64, dd, H 30; 7 16–7 94, m, Ph. 13C n.m.r.
(75 5 MHz) 17 46, C 60; 67 84, 70 99, 73 44, 74 88, 75 47,
5C, C 6, CH2Ph; 70 37, 72 70, 73 13, 74 00, 74 46, 76 93,
81 79, 82 82, 8C, C 2,3,4,5,20,30,40,50; 100 16, C 10; 102 46,
C 1; 127 28–139 04, Ph; 164 85, 165 40, 165 76, 3C, CO.
(b) The tribenzoate (35) (119 mg, 222 mol) and benzyl
2,3,6-tri-O-benzyl- -D-glucopyranoside (16) (100 mg, 185 mol)
were treated as described in procedures (a) then (b) as above
to give, after ash chromatography (0–5% EtOAc/toluene),
the deoxy sugar (37) as a clear oil (118 mg, 64%). This
material gave identical 1H (300 MHz) and 13C n.m.r. (75 5
MHz) spectra to the material prepared as outlined above.
0
0
0
0
H 30; 7 16–7 55, 7 78–7 98, 2m, Ph. 13C n.m.r. (75 5 MHz)
17 69, C 6; 40 11, C 60; 56 87, OMe; 70 55, C 5; 71 70, C 40;
72 63, C 20; 72 92, C 50; 72 94, C 30; 74 59, 74 66, 2C, CH2Ph;
82 12, C 2; 82 23, C 3; 82 92, C 4; 100 57, C 10; 104 19, C 1;
127 00–129 63, 133 10–133 43, 138 54, 139 34, Ph; 164 89,
165 15, 165 63, 3C, CO.
Dibenzyl 4,40-O-[6,6 0-Dithiobis(2,3,4-tri-O-benzoyl-6-deoxy-
-D-glucosyl)]bis(2,3,6-tri-O-benzyl- -D-glucoside) (22)
The tribenzoate (10) (436 mg, 888 mol) and benzyl 2,3,6-
tri-O-benzyl- -D-glucopyranoside (16)20 (400 mg, 741 mol)
were treated as described in procedure (a) above to give, after
ash chromatography (5% EtOAc/toluene), the disul de (22)
as a syrup (623 mg, 82%), [ ]D +28 3 (Found: C, 71 0; H,
1,2:3,4-Di-O-isopropylidene-6-O-(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)- -D-galactose (38)
5 5.
(500 MHz) 2 40, dd, J5 ,6
dd, J5 ,6
2 7 Hz, H 60; 3 24, m, H 5; 3 54, dd, J1,2 7 7, J2,3
C
122H114O26S2 requires C, 71 1; H, 5 6%). 1H n.m.r.
8 1, J6 ,6
14 3 Hz, H 60; 2 56,
The tribenzoate (35) (141 mg, 263 mol) and 1,2:3,4-di-
O-isopropylidene- -D-galactose (5) (57 mg, 220 mol) were
treated as described in procedures (a) then (b) as above to
give, after ash chromatography (5–10% EtOAc/toluene), the
deoxy disaccharide (38) as a clear oil (115 mg, 73%), [ ]D
33 0 (Found: C, 65 0; H, 6 0. C39H42O13 requires C,
65 2; H, 5 9%). 1H n.m.r. (500 MHz) 1 21, 1 25, 1 42, 3s,
0
0
0
0
0
0
9 1 Hz, H 2; 3 60, dd, J3,4 8 8 Hz, H 3; 3 61, dd, J5,6 1 8,
J6,6 10 9 Hz, H 6; 3 71, dd, J5,6 3 6 Hz, H 6; 3 77, ddd,
J4 ,5
m, 8H, CH2Ph; 4 44, d, H 1; 4 85, d, J1 ,2
5 20, dd, J3 ,4
9 5 Hz, H 40; 5 40, dd, J2 ,3
0
9 5 Hz, H 50; 4 13, dd, J4,5 9 7 Hz, H 4; 4 41–5 06,
0
0
0
8 0 Hz, H 10;
9 8 Hz, H 20;
0
0
0
0
12H, CMe2; 1 37, d, J5 ,6
0 0
6 2 Hz, 3H, H 60; 3 82, dd, J5,6
6 7, J6,6 11 1 Hz, H 6; 3 85–3 90, m, H 5,50; 4 03, dd, J5,6
5 0 Hz, H 6; 4 14, dd, J3,4 7 9, J4,5 1 8 Hz, H 4; 4 21, dd,
5 60, dd, H 30; 7 19–7 93, m, Ph. 13C n.m.r. (75 5 MHz)
39 68, C 60; 67 58, 70 83, 73 61, 74 72, 74 87, 5C, C 6,
CH2Ph; 71 98, 72 45, 72 80, 72 99, 74 37, 76 58, 81 60,
82 42, C 2,3,4,5,20,30,40,50; 99 66, C 10; 102 44, C 1; 127 01–
129 63, 133 05–133 43, 137 53–139 46, Ph; 164 73, 165 19,
165 56, 3C, CO. High-resolution mass spectrum (f.a.b.) m/z
2059 494 [C122H114O26S2 (M+ ) requires 2058 704].
J1,2 5 0, J2,3 2 4 Hz, H 2; 4 44, dd, H 3; 4 93, d, J1 ,2
Hz, H 10; 5 33, dd, J3 ,4 9 6 Hz, H 40; 5 42, d,
9 6, J4 ,5
H 1; 5 49, dd, J2 ,3
9 8 Hz, H 20; 5 82, dd, H 30; 7 23–8 00,
0
0
8 0
0
0
0
0
0
0
m, 15H, Ph. 13C n.m.r. (125 8 MHz) 17 46, C 60; 24 08,
24 73, 25 60, 25 80, 4C, CMe2; 67 14, C 5; 67 94, C 6; 70 30,
C 2; 70 39, C 3; 70 45, C 50; 70 79, C 4; 71 92, C 20; 72 94,
C 30; 73 88, C 40; 96 06, C 1; 101 99, C 10; 108 32, 109 09, 2C,
CMe2; 128 07–129 85, 132 87–133 22, Ph; 165 06, 165 34,
165 74, 3C, CO. High-resolution mass spectrum (f.a.b.) m/z
717 2567 [C39H41O13 (M H)+ requires 717 2547].
Dibenzyl 4,4 0-O-[6,6 0-Diselenobis(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)]bis(2,3,6-tri-O-benzyl- -D-glucoside)
(36)
The tribenzoate (35) (238 mg, 443 mol) and benzyl 2,3,6-
tri-O-benzyl- -D-glucopyranoside (16) (200 mg, 370 mol) were
treated as described in procedure (a) above to give, after ash
chromatography (0–5% EtOAc/toluene), the diselenide (36) as
a yellow oil (214 mg, 54%), [ ]D +49 9 (Found: C, 67 9; H,
5 3. C122H114O26Se2 requires C, 68 0; H, 5 3%). 1H n.m.r.
Methyl 2,4,6-Tri-O-benzyl-3-O-(2,3,4-tri-O-benzoyl-6-deoxy-
-D-glucosyl)- -D-glucoside (39)
The tribenzoate (35) (132 mg, 246 mol) and methyl 2,4,6-
tri-O-benzyl- -D-glucoside (14) (95 mg, 205 mol) were treated
as described in procedures (a) then (b) as above to give, after
(300 MHz) 2 64, dd, J5 ,6 8 5, J6 ,6
0 0 0
13 0 Hz, H 60; 2 74,
0

1,6-Epithio- and 1,6-Episeleno- -D-glucopyranose
691
ash chromatography (5% EtOAc/toluene), the deoxy disac-
charide (39) as a clear syrup (103 mg, 55%), [ ]D 34 2
(Found: C, 71 4; H, 5 9. C55H54O13 requires C, 71 6; H,
ash chromatography (35% EtOAc/petrol), the disul de (28)
as a pale-yellow oil (113 mg, 90%), [ ]D +39 3 (Found: C,
65 6; H, 6 1. C92H102O26S2 requires C, 65 5; H, 6 1%). 1H
5 9%). 1H n.m.r. (300 MHz) 1 23, d, J5 ,6
0
0
6 2 Hz, 3H, H 60;
n.m.r. (500 MHz)
1 88, 1 90, 1 93, 3s, 9H, OAc; 2 37,
13 9 Hz, H 60; 2 53, dd, J5 ,6
3 16, s, OMe; 3 24, dd, J1,2 3 6, J2,3 9 5 Hz, H 2; 3 44–3 64,
m, 4H, H 4,5,6; 3 76, dq, J4 ,5
9 6 Hz, H 50; 4 05–5 06, m,
6H, CH2Ph; 4 19, d, H 1; 4 29, dd, J3,4 J4,5 9 1 Hz, H 3;
5 28, dd, J3 ,4
9 6 Hz, H 40; 5 36, d, J1 ,2 6 7 Hz, H 10;
5 50, dd, J2 ,3
9 8 Hz, H 20; 5 79, dd, H 30; 7 00–7 95, Ph.
13C n.m.r. (75 5 MHz) 17 46, C 60; 54 94, OMe; 68 36,
dd, J5 ,6 7 0, J6 ,6 3 7 Hz,
0
0
0
0
0
0
0
0
H 60; 3 25, br d, J4,5 9 8 Hz, H 5; 3 32–3 49, m, H 2,3,50;
3 62–3 70, m, 2H, H 6; 3 89, dd, J3,4 8 7 Hz, H 4; 4 39, d,
0
0
0
0
J1,2 7 4 Hz, H 1; 4 40–4 89, m, 8H, CH2Ph; 4 50, d, J1 ,2
8 0 Hz, H 10; 4 74–4 82, m, H 20,40; 4 92, dd, J2 ,3
J3 ,4
9 4 Hz, H 30; 7 14–7 36, m, Ph. 13C n.m.r. (75 5 MHz)
0
0
0
0
0
0
0
0
73 50, 73 81, 75 07, C 6, CH2Ph; 69 48, 70 25, 72 95, 73 14,
74 15, 75 43, 78 44, 80 75, C 2,3,4,5,20,30,40,50; 97 74, C 1;
100 41, C 10; 127 62–129 78, 133 06–133 27, 137 82–138 38,
Ph; 165 17, 165 49, 165 84, 3C, CO.
20 55, 20 71, 20 89, 3C, Me; 40 83, C 60; 67 62, 70 94, 72 97,
74 84, 74 88, 5C, C 6, CH2Ph; 71 24, 72 12, 72 97, 74 66,
76 68, 81 69, 82 30, 8C, C 2,3,4,5,20,30,40,50; 127 10–128 64,
137 75–139 22, Ph; 169 08, 169 66, 170 11, 3C, CO.
Deprotection and Deoxygenation of the Disul des
General Procedure for the Preparation of the Thioacetates
(29)–(31)
General Procedure for the Deacylation and Acetylation of
the Tribenzoates (11), (18) and (22)
A solution of the disul de in dry tetrahydrofuran/MeOH
(1 : 1, 10 ml) was treated with a small piece of sodium metal.
The solution was left to stand overnight under N2. The
solvent was evaporated and the residual oil was taken up in
dry tetrahydrofuran (5 ml) and liquid ammonia (20 ml) added
at 78 . Small pieces of sodium metal were added until the
mixture went blue and remained so for 1 h. NH4OAc (0 5 g)
was then added and the ammonia allowed to evaporate under
A solution of the disul de in the speci ed solvent was treated
with a small piece of sodium metal overnight. The solvent was
evaporated and the residue treated with pyridine (3 ml), Ac2O
(2 ml) and 4-(dimethylamino)pyridine (5 mg). The solvent
was evaporated and the residue subjected to the usual workup
(CH2Cl2). The residue was puri ed by ash chromatography
to a ord the per -acetates.
a
ow of N2. The residue was treated with Ac2O (1 ml),
6,6 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-acetyl-6-deoxy- -D-
glucosyl)]bis(1,2:3,4-di-O-isopropylidene- -D-galactose)
(24)
pyridine (3 ml) and 4-(dimethylamino)pyridine (2 mg) at room
temperature overnight. The solvent was evaporated and the
residue was subjected to the usual workup (CH2Cl2) to give
a residue which was puri ed by ash chromatography to give
the various thioacetates in the indicated yield.
The disul de (11) (286 mg) dissolved in dry MeOH (5
ml) was treated as above to yield, after ash chromatography
(40–50% EtOAc/petrol), the disul de (24) as a clear syrup (175
mg, 81%), [ ]D 6 6 (Found: C, 51 3; H, 6 4. C48H70O26S2
Methyl 2,3,4-Tri-O-acetyl-6-O-(2,3,4-tri-O-acetyl-6-S-
acetyl-6-thio- -D-glucosyl)- -D-glucoside (29)
requires C, 51 1; H, 6 3%). 1H n.m.r. (300 MHz)
1 26,
1 28, 1 40, 1 44, 4s, 12H, CMe2; 1 99, 2 00, 2 01, 3s, 9H, Ac;
The disul de (19) (203 mg) was treated according to the
procedure above to give, after ash chromatography (40%
EtOAc/petrol), the thioacetate (29) as a clear oil (85 mg, 60%),
[ ]D +62 6 (Found: C, 48 7; H, 6 0. C27H38O17S requires
C, 48 7; H, 5 8%). 1H n.m.r. (300 MHz) 1 94, 1 94, 1 98,
2 78, dd, J5 ,6 7 6, J6 ,6 3 3
13 8 Hz, H 60; 2 88, dd, J5 ,6
0 0 0 0 0
0
Hz, H 60; 3 62–3 70, m, H 50; 3 64, dd, J5,6 7 6, J6,6 11 4
Hz, H 6; 3 85–3 90, m, H 5; 3 97, dd, J5,6 3 4 Hz, H 6; 4 15,
dd, J3,4 7 9, J4,5 1 8 Hz, H 4; 4 24, dd, J1,2 5 0, J2,3 2 5
7 9 Hz, H 10; 4 89, dd,
9 6 Hz, H 20;
1 99, 2 01, 2 02, 6s, 18H, OAc; 2 29, s, SAc; 2 99, dd, J5 ,6
7 0, J6 ,6
14 3 Hz, H 60; 3 20, dd, J5 ,6 2 9 Hz, H 60; 2 29,
s, 3H, OMe; 3 48, dd, J5,6 4 7, J6,6 11 0 Hz, H 6; 3 56, dd,
J4 ,5
9 9 Hz, H 50; 3 83, J5,6 2 1 Hz, H 6; 3 90, m, H 5; 4 46,
d, J1 ,2
8 0 Hz, H 10; 4 79, dd, J1,2 3 6, J2,3 10 2 Hz, H 2;
4 86–4 95, H 1,4,20,40; 5 12, t, J2 ,3 9 4 Hz, H 30;
J3 ,4
0
0
Hz, H 2; 4 54, dd, H 3; 4 56, d, J1 ,2
0
0
9 5 Hz, H 40; 4 92, dd, J2 ,3
0
0
0
0
0
0
J3 ,4 9 5, J4 ,5
0
0
0
0
5 15, dd, H 30; 5 45, d, H 1. 13C n.m.r. (75 5 MHz) 20 53,
20 59, 3C, COMe; 24 35, 24 96, 25 91, 25 96, 4C, CMe2;
41 06, C 60; 67 81, 70 37, 70 57, 71 16, 71 46, 72 10, 72 55,
8C, C 2,3,4,5,20,30,40,50; 69 44, C 6; 96 11, C 1; 101 37, C 10;
108 54, 109 37, 2C, CMe2; 169 44, 169 65, 170 07, 3C, CO.
0
0
0
0
0
0
0
0
5 40, dd, J3,4 9 3 Hz, H 3. 13C n.m.r. (75 5 MHz) 20 49,
20 57, 6C, OCOMe; 30 03, SCOMe; 30 30, C 60; 55 18, OMe;
67 92, C 6; 68 16, 68 95, 70 11, 70 64, 70 77, 71 12, 72 57,
73 03, C 2,3,4,5,20,30,40,50; 96 42, C 1; 100 67, C 10; 169 22,
169 56, 169 64, 169 94, 170 02, 170 10, 6C, OCO; 194 48,
SCO.
Dimethyl 6,6 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-acetyl-6-deoxy-
-D-glucosyl)]bis(2,3,4-tri-O-acetyl- -D-glucoside) (25)
The disul de (18) (163 mg) dissolved in dry MeOH (3
ml) was treated as above to yield, after ash chromatography
(55–60% EtOAc/petrol), the disul de (25) as a clear syrup
(97 mg, 77%), [ ]D +106 5 . 1H n.m.r. (300 MHz) 1 93,
1 94, 1 97, 1 99, 2 00, 2 01, 6s, 18H, Ac; 2 77–2 84, m, 2H,
H 60; 3 50, dd, J5,6 5 6, J6,6 10 8 Hz, H 6; 3 65, m, H 50;
Methyl 2,4,6-Tri-O-acetyl-3-O-(2,3,4-tri-O-acetyl-6-S-
acetyl-6-thio- -D-glucosyl)- -D-glucoside (30)
The disul de (20) (225 mg) was treated according to the
procedure above to give, after ash chromatography (40–50%
EtOAc/petrol), the thioacetate (30) as a clear oil (90 mg, 57%),
[ ]D +28 0 (Found: C, 48 6; H, 6 0. C27H38O17S requires
C, 48 6; H, 5 8%). 1H n.m.r. (300 MHz) 1 91, 1 92, 2 02,
3 85–3 94, m, H 5,6; 4 49, d, J1 ,2
J1,2 3 6, J2,3 10 2 Hz, H 2; 4 85–4 96, m, H 1,4,20,40; 5 15, t,
J2 ,3 J3 ,4
9 5 Hz, H 30; 5 40, dd, J3,4 9 7 Hz, H 3. 13C
n.m.r. (75 5 MHz)
20 49, 20 58, 6C, COMe; 40 99, C 60;
0
0
7 9 Hz, H 10; 4 79, dd,
0
0
0
0
55 20, OMe; 67 75, C 6; 68 04, 68 75, 70 11, 70 72, 71 19,
71 37, 72 36, 72 49, C 2,3,4,5,20,30,40,50; 96 42, C 1; 100 63,
C 10; 169 25, 169 46, 169 60, 169 96, 6C, CO. High-resolution
2 05, 2 13, 5s, 18H, OAc; 2 32, s, SAc; 2 99, dd, J5 ,6
J6 ,6
14 3 Hz, H 60; 3 20, dd, J5 ,6 2 9 Hz, H 60; 3 37, s,
OMe; 3 53, ddd, J4 ,5
9 8 Hz, H 50; 3 89, ddd, J4,5 10 2,
J5,6 2 4, 4 6 Hz, H 5; 4 02–4 11, m, H 3,6; 4 16, dd, J6,6
12 3 Hz, H 6; 4 59, d, J1 ,2
8 1 Hz, H 10; 4 78–4 86, m,
H 1,2,20; 4 90, dd, J3 ,4 10 0 Hz, H 40; 4 95, dd, J3,4 9 3 Hz,
9 4 Hz, H 30. 13C n.m.r. (75 5 MHz)
0
0
6 9,
0
0
0
0
0
0
mass spectrum (f.a.b.) m/z 1246 3292 [C50H70O32S2 (M+
)
requires 1246 3290].
0
0
0
0
Dibenzyl 4,4 0-O-[6,6 0-Dithiobis(2,3,4-tri-O-acetyl-6-deoxy-
-D-glucosyl)]bis(2,3,6-tri-O-benzyl- -D-glucoside) (28)
0
0
H 4; 5 03, dd, J2 ,3
20 25, 20 50, 20 59, 20 70, 20 79, 20 92, 6C, OCOMe; 30 05,
C 60; 30 37, SCOMe; 55 34, OMe; 62 04, C 6; 67 34, 67 81,
70 31, 71 24, 72 83, 72 91, 75 95, C 2,3,4,5,20,30,40,50; 96 67,
The disul de (22) (153 mg) dissolved in dry tetrahydrofu-
ran/MeOH (1 : 1, 10 ml) was treated as above to yield, after

692
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
C 1; 100 41, C 10; 168 98, 169 59, 169 75, 170 29, 170 68, 6C,
OCO; 194 42, SCO.
C24H36O13 requires C, 54 1; H, 6 8%). 1H n.m.r. (500 MHz)
1 20, d, J5 ,6
0
8 0 Hz, 3H, H 60; 1 29, 1 29, 1 41, 1 47, 4s,
0
12H, CMe2; 1 96, 2 00, 2 03, 3s, 9H, Ac; 3 53, dq, J4 ,5 9 7
0
0
Hz, H 50; 3 63, dd, J5,6 7 4, J6,6 11 3 Hz, H 6; 3 89, m, H 5;
3 98, dd, J5,6 3 7 Hz, H 6; 4 15, dd, J3,4 7 9, J4,5 1 9 Hz,
1,2,3,6-Tetra-O-acetyl-4-O-(2,3,4-tri-O-acetyl-6-S-acetyl-6-
thio- -D-glucosyl)- -D-glucose (31)
H 4; 4 25, dd, J1,2 5 0, J2,3 2 4 Hz, H 2; 4 53, d, J1 ,2
Hz, H 10; 4 55, dd, H 3; 4 57, dd, J3 ,4 9 6 Hz, H 40; 4 94, dd,
J2 ,3
9 8 Hz, H 20; 5 13, dd, H 30; 5 47, d, H 1. 13C n.m.r.
0
0
8 0
(a) The disul de (22) (145 mg) was treated according to
the procedure above to give, after ash chromatography (50%
EtOAc/petrol), a clear oil (63 mg, 64%).
0
0
0
0
(125 8 MHz) 17 31, C 60; 20 65, 20 69, 3C, COMe; 24 27,
25 01, 25 90, 26 01, 4C, CMe2; 67 67, 69 88, 70 42, 70 59,
71 20, 71 39, 72 72, 73 52, C 2,3,4,5,20,30,40,50; 69 35, C 6;
96 17, C 1; 101 27, C 10; 108 62, 109 33, 2C, CMe2; 169 61,
169 70, 170 31, 3C, CO.
(b) A portion of the above mixture (49 mg) was treated
with a solution of fused zinc chloride (100 mg) in Ac2O at 100
under Argon for 30 min. The brown solution was poured into
ice-water and stirred for 10 min. The mixture was extracted
with EtOAc and the organic extract washed with saturated
aqueous NaHCO3 and brine, then dried. The solvent was
evaporated and the residue crystallized to give the thioacetate
(31) as needles (29 mg, 59%), m.p. 216–218 (EtOAc/EtOH),
[ ]D +23 (Found: C, 48 5; H, 5 5. C28H38O18S requires C,
Methyl 2,3,4-Tri-O-acetyl-6-O-(2,3,4-tri-O-acetyl-6-deoxy-
-D-glucosyl)- -D-glucoside (27)
(a) The thioacetate (29) (69 mg) and Raney nickel (1 g; 6
h) yielded the deoxy disaccharide (27) as a pale brown oil (43
mg, 67%) that crystallized as plates, m.p. 158–160 (EtOH),
[ ]D +70 8 (Found: C, 50 4; H, 6 0. C25H36O16 requires C,
48 4; H, 5 5%). 1H n.m.r. (300 MHz)
1 95, 1 99, 2 01,
2 04, 2 05, 2 11, 2 15, 7s, 21H, OAc; 2 35, s, SAc; 3 05, dd,
J5 ,6
0
3 56, ddd, J4 ,5
0
6 9, J6 ,6
0
0
14 5 Hz, H 60; 3 22, dd, J5 ,6
9 6 Hz, H 50; 3 78, t, J3,4
0
0
3 1 Hz, H 60;
J4,5 9 7 Hz,
50 7; H, 6 1%). 1H n.m.r. (300 MHz) 1 21, d, J5 ,6 6 2
Hz, 3H, H 60; 1 95, 1 96, 1 99, 2 00, 2 01, 2 03, 6s, 18H, Ac;
3 35, s, OMe; 3 51, dd, J5,6 6 9, J6,6 10 0 Hz, H 6; 3 53,
0
0
0
0
H 4; 3 97, m, H 5; 4 09, dd, J5,6 4 3, J6,6 12 2 Hz, H 6; 4 45,
d, J1 ,2
7 9 Hz, H 10; 4 44–4 48, m, H 6; 4 88, dd, J2 ,3
9 3 Hz, H 20; 4 95, dd, J3 ,4 9 7 Hz, H 40; 5 01, dd, J1,2
0
0
0
0
dq, J4 ,5 10 1 Hz, H 50; 3 87, dd, J5,6 2 1 Hz, H 6; 3 91, m,
0
0
0
0
3 8, J2,3 10 3 Hz, H 2; 5 10, dd, H 30; 5 42, dd, H 3; 6 24,
d, H 1. 13C n.m.r. (75 5 MHz) 20 53, 20 59, 20 65, 20 79,
20 93, 21 00, 7C, OCOCH3; 29 99, C 60; 30 44, SCOCH3;
61 34, C 6; 69 19, 69 49, 70 19, 70 82, 71 72, 72 92, 73 45,
75 45, C 2,3,4,5,20,30,40,50; 88 97, C 1; 100 38, C 10; 168 91,
169 04, 169 66, 169 95, 170 18, 7C, OCO; 194 24, SCO. High-
0
0
H 5; 4 48, d, J1 ,2 7 9 Hz, H 10; 4 78, t, J3,4
H 4; 4 81, dd, J1,2 3 6, J2,3 10 2 Hz, H 2; 4 88, d, H 1; 4 89,
J4,5 9 5 Hz,
dd, J3 ,4 10 1 Hz, H 40; 4 95, dd, J2 ,3 9 6 Hz, H 20; 5 12,
dd, H 30; 5 42, dd, H 3. 13C n.m.r. (75 5 MHz) 17 26, C 60;
20 63, 6C, COMe; 55 22, OMe; 67 86, C 6; 68 13, 69 00,
70 07, 70 15, 70 82, 71 40, 72 75, 73 31, C 2,3,4,5,20,30,40,50;
96 43, C 1; 100 65, C 10; 169 35, 169 62, 170 03, 170 29, 6C,
CO.
0
0
0
0
resolution mass spectrum (f.a.b.) m/z 695 0897 [C28H39O18
(M+H)+ requires 695 1856].
S
(b) The disul de (25) (47 mg) and Raney nickel (0 5 g;
1 5 h) yielded the deoxy disaccharide (27) as a pale yellow oil
(35 mg, 75%). This material was identical by 1H n.m.r. (300
MHz) spectroscopy to that prepared above.
General Procedure for the Reduction of the Disul des (21),
(24) and (25) and the Thioacetates (29)–(31) with Raney
Nickel
A solution of the thioacetate or disul de in EtOH (5–10 ml)
was treated with Raney nickel under re ux for the speci ed time.
The reaction mixture was cooled and ltered through Celite
and the ltrate evaporated. The residue was passed through a
short plug of silica (EtOAc) and the solvent evaporated from
the eluate to a ord the deoxy disaccharides.
Methyl 2,4,6-Tri-O-acetyl-3-O-(2,3,4-tri-O-acetyl-6-deoxy-
-D-glucosyl)- -D-glucoside (32)
The thioacetate (30) (71 mg) and Raney nickel (0 5 g;
2 h) yielded the deoxy disaccharide (32) as a light brown
oil (56 mg, 85%). The colour was removed by careful ash
chromatography (40% EtOAc/petrol) to give a clear oil which
crystallized, m.p. 190–193 (EtOH), [ ]D +37 9 (Found: C,
Methyl 2,3-Di-O-benzyl-6-deoxy-4-O-(2,3,4-tri-O-benzoyl-6-
deoxy- -D-glucosyl)- -D-glucoside (23)
50 4; H, 6 0.
n.m.r. (300 MHz)
1 93, 1 99, 2 00, 2 05, 2 13, 6s, 18H, Ac; 3 37, s, OMe; 3 48,
dq, J4 ,5
9 7 Hz, H 50; 3 88, ddd, J4,5 10 3, J5,6 2 4, 4 4 Hz,
H 5; 4 04–4 11, m, H 3,6; 4 16, dd, H 6; 4 56, d, J1 ,2 8 1
Hz, H 10; 4 74, dd, J3 ,4 9 5 Hz, H 40; 4 79–4 83, m, H 1,20;
4 85, dd, J1,2 3 5, J2,3 9 9 Hz, H 2; 4 94, dd, J3,4 9 2 Hz,
C
25H36O16 requires C, 50 7; H, 6 1%). 1H
1 17, d, J5 ,6
6 2 Hz, 3H, H 60; 1 92,
0
0
The disul de (21) (88 mg) and Raney nickel (0 5 g; 1 h)
yielded a clear residue which was puri ed by ash chromato-
graphy (5% EtOAc/toluene) to give the dideoxy disaccharide
(23) as a clear oil (71 mg, 84%). A small portion was taken
and crystallized to give akes, m.p. 139–140 (CH2Cl2/petrol),
[ ]D +7 5 (Found: C, 70 7; H, 6 0. C48H48O12 requires C,
0
0
0
0
0
0
H 4; 5 03, dd, J2 ,3
0
8 3 Hz, H 30. 13C n.m.r. (75 5 MHz)
0
70 6; H, 5 9%). 1H n.m.r. (300 MHz) 1 16, d, J5,6
0 0
J5 ,6
17 43, C 60; 20 34, 20 61, 20 72, 20 80, 20 94, 6C, COMe;
55 34, OMe; 62 11, C 6; 67 33, 68 06, 69 78, 71 73, 72 65,
73 05, 73 26, 75 93, C 2,3,4,5,20,30,40,50; 96 78, C 1; 100 39,
C 10; 169 12, 169 56, 169 81, 170 41, 170 71, 6C, CO.
6 0 Hz, 6H, H 6,60; 3 27, dq, J4,5 9 4 Hz, H 5; 3 39, dd, J1,2
7 8, J2,3 9 0 Hz, H 2; 3 45, dd, J3,4 9 4 Hz, H 4; 3 49, s,
OMe; 3 61, dd, H 3; 3 64, dq, J4 ,5
H 1; 4 64–5 03, m, 4H, CH2Ph; 5 08, d, J1 ,2
8 0 Hz, H 10;
5 28, dd, J3 ,4
0
9 9 Hz, H 40; 5 49, dd, J2 ,3 9 9 Hz, H 20;
0
9 9 Hz, H 50; 4 22, d,
0
0
0
0
0
0
5 75, dd, H 30; 7 16–7 98, m, Ph. 13C n.m.r. (75 5 MHz)
17 44, 17 69, C 6,60; 56 99, OMe; 70 59, 70 62, 72 91, 73 09,
73 75, 82 32, 82 84, 83 53, C 2,3,4,5,20,30,40,50; 101 26, C 10;
104 33, C 1; 127 08–129 69, 133 10–133 29, 138 48, 139 11,
Ph; 165 01, 165 39, 165 82, 3C, CO.
1,2,3,6-Tetra-O-acetyl-4-O-(2,3,4-tri-O-acetyl-6-deoxy- -D-
glucosyl)- -D-glucose (33)
The thioacetate (31) (18 5 mg) and Raney nickel (0 5 g; 1
h) yielded the deoxy disaccharide (33) as a white, crystalline
solid (14 mg, 85%). This material crystallized as white needles,
m.p. 225 5–226 (EtOH; lit.21 185–186 ), [ ]D +57 7 (lit.21
+25 3 ) (Found: C, 50 5; H, 5 7. Calc. for C26H36O17: C,
1,2:3,4-Di-O-isopropylidene-6-O-(2,3,4-tri-O-acetyl-6-
deoxy- -D-glucosyl)- -D-galactose (26)
50 3; H, 5 8%). 1H n.m.r. (300 MHz) 1 23, d, J5 ,6
Hz, 3H, H 60; 1 95, 1 98, 2 01, 2 02, 2 10, 2 15, 6s, 21H, Ac;
3 50, dq, J4 ,5 J4,5 9 6 Hz, H 4;
9 7 Hz, H 50; 3 76, t, J3,4
3 96, ddd, J5,6 2 0, 4 2 Hz, H 5; 4 08, dd, J6,6 12 1 Hz, H 6;
4 45, d, J1 ,2 9 7
8 0 Hz, H 10; 4 45, dd, H 6; 4 78, dd, J3 ,4
0
0
6 2
The disul de (24) (106 mg) and Raney nickel (2 g; 1 5
h) yielded the deoxy disaccharide (26) as a white, crystalline
solid (69 mg, 69%). Recrystallization a orded needles, m.p.
163 5–165 (EtOH), [ ]D 62 8 (Found: C, 53 9; H, 6 6.
0
0
0
0
0
0

1,6-Epithio- and 1,6-Episeleno- -D-glucopyranose
693
8
Hz, H 40; 4 89, dd, J2 ,3
0
0
9 5 Hz, H 20; 4 99, dd, J1,2 3 8, J2,3
Lundt, I., and Skelb k-Pedersen, B., Acta Chem. Scand.,
Ser. B, 1981, 35, 637.
Toshima, K., and Tatsuta, K., Chem. Rev., 1993, 93, 1503.
Ziegler, T., Kovac, P., and Glaudemans, C. P. J., Liebigs
Ann. Chem., 1990, 613.
Fukase, K., Kinoshita, I., Kanoh, T., Nakai, Y., Hasuoka,
A., and Kusumoto, S., Tetrahedron, 1996, 52, 3897.
Kartha, K. P. R., and Field, R. A., Tetrahedron Lett., 1997,
38, 8233.
Konradsson, P., Udodong, U. E., and Fraser-Reid, B.,
Tetrahedron Lett., 1990, 31, 4313.
Garegg, P. J., and Norberg, T., Acta Chem. Scand., Ser.
B, 1979, 33, 116.
Stick, R. V., Tilbrook, D. M. G., and Williams, S. J., Aust.
J. Chem., 1997, 50, 237.
Horton, D., and Lauterback, J. H., J. Org. Chem., 1969,
34, 86.
Eby, R., and Schuerch, C., Carbohydr. Res., 1974, 34, 79.
Koto, S., Takebe, Y., and Zen, S., Bull. Chem. Soc. Jpn,
1972, 45, 291.
McAuli e, J. C., and Stick, R. V., Aust. J. Chem., 1997,
50, 197.
Petit, J.-M., and Sinay, P., Carbohydr. Res., 1978, 64, 9.
Jezo, I., and Zemek, J., Chem. Pap., 1986, 40, 839.
McAuli e, J. C., and Stick, R. V., Aust. J. Chem., 1997,
50, 193.
Augustine, R. L., ‘Catalytic Hydrogenation’ pp. 147–148
(Marcel Dekker: New York 1965).
Dasgupta, F., and Garegg, P. J., Acta Chem. Scand., 1989,
43, 471.
10 4 Hz, H 2; 5 08, dd, H 30; 5 41, dd, H 3; 6 22, d, H 1. 13C
n.m.r. (75 5 MHz) 17 54, C 60; 20 47, 20 58, 20 81, 20 91,
21 05, 7C, COCH3; 61 41, C 6; 69 35, 69 61, 70 16, 70 76,
72 07, 72 95, 76 10, C 2,3,4,5,20,30,40,50; 88 99, C 1; 100 83,
C 10; 168 92, 169 18, 169 52, 169 58, 169 93, 170 29, 7C, CO.
9
10
11
12
13
14
15
16
Acknowledgments
We thank the Australian Research Council for nan-
cial assistance and Dr J. C. McAuli e and Dr W.
M. Best for the supply of some of the carbohydrate
alcohols.
17
18
References
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7