β-Acarbose. VIII the synthesis of some N-linked carba-oligosacchandes

Article abstract of DOI:10.1071/CH99031

Two carbohydrate triflates have been used to alkylate a 1-epivalienamine derivative to give small amounts of the desired secondary amines, in addition to amounts of the products of elimination. Deprotection of the secondary amines afforded a carba-disacch

Full text of DOI:10.1071/CH99031

C S I R O P U B L I S H I N G
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Volume 52, 1999
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Aust. J. Chem., 1999, 52, 895–904
-Acarbose. VIII†
The Synthesis of Some N-Linked Carba-Oligosaccharides
Robert V. Stick,A,B D. Matthew G. TilbrookA and Spencer J. WilliamsA
A Department of Chemistry, The University of Western Australia,
Nedlands, W.A. 6907.
B Author to whom correspondence should be addressed.
Two carbohydrate triflates have been used to alkylate a 1-epivalienamine derivative to give small amounts of the
desired secondary amines, in addition to amounts of the products of elimination. Deprotection of the secondary
amines afforded a carba-disaccharide and a carba-tetrasaccharide which have been shown to be good inhibitors of
-glucosidases.
The previous seven papers in this series have described a
number of approaches to the synthesis of -linked carba-
sugars as potential inhibitors of enzymes which process -D-
glucosidic linkages. The preceeding paper in this series
described an unsuccessful attempt at the preparation of our
ultimate target, methyl -acarboside (1), from which arose
this final, successful approach.
The route used to prepare the anhydro D-glucitol (7) began
with phenyl 1-thio- -D-galactopyranoside, easily prepared
from D-galactopyranose pentaacetate.5,6 Treatment of phenyl
1-thio- -D-galactopyranoside with 2,2-dimethoxypropane
and p-toluenesulfonic acid gave, after chromatography, the
diol (10)7 in an almost quantitative yield. Treatment of the
diol (10) with Raney nickel, at reflux in ethanol, cleanly fur-
nished the 1,5-anhydro D-galactitol (11).7 Iodination of the
primary alcohol of (11) according to the procedure of Garegg
and Samuelsson gave the highly crystalline iodide (12).8
Reduction of the iodide (12) was first attempted with
lithium aluminium hydride in tetrahydrofuran. The reaction
was complicated by the formation of a major by-product,
shown to be the isopropyl ether (13), in addition to the
desired deoxy sugar (14). The structure of (13) was con-
firmed by conversion into the diacetate (15), with a con-
comitant downfield shift in the signals assigned to H2 and
H3. The cleavage of the isopropylidene moiety in (12) was
somewhat surprising; the reduction of acetals of this form
usually requires Lewis acid catalysis.9–11 In this case it is
probable that the aluminium hydride ion and the hydroxy
group of (12) generated an aluminium alkoxide; an
intramolecular hydride transfer could then take place to
afford the isopropyl ether (13).12
A new strategy for the preparation of methyl -acarboside
(1) was planned, involving the alkylation of the amine (2)
with the triflate (3). This synthetic route was based on results
recently obtained in this laboratory. In earlier work, it was
noted that an attempted alkylation of tetra-O-benzyl-1-epi-
valienamine (2) with a range of D-galacto triflates possess-
ing neighbouring benzyl ether protecting groups provided no
products of alkylation; instead, mixtures of 3,4- and 4,5-
elimination products were obtained.1 More recently, during
systematic studies, it was observed that the introduction of a
benzoic acid ester at C3 reduced the tendency for the triflate
(4) to eliminate in the 3,4-sense, enabling the synthesis of the
carba-disaccharide (5) in 43% yield, with the only by-
product being the 4,5-alkene (6) (24%).2 The use of benzoic
acid esters adjacent to leaving groups such as triflates for the
alkylation of other nucleophiles has been noted previously.3
Initially, however, a preliminary target, the N-linked
carba-disaccharide (7), was set. The carba-disaccharide (7)
was of interest for two reasons. Firstly, it allowed for the
preparation of a much simpler molecule using a route analo-
gous to that planned for the carba-tetrasaccharide (1).
Secondly, the carba-disaccharide (7) was a putative inhibitor
of -glucan hydrolases, particularly as the absence of a gly-
cosidic linkage in the inhibitor should preclude detrimental
enzymatic hydrolysis, expected for analogues such as (8)
and (9).2,4
Treatment of the iodide (12) with tributylstannane avoided
the above problem and provided the requisite deoxy sugar (14)
in an excellent yield. The introduction of benzoyl groups at O2
and O3 was achieved in a stepwise fashion, as outlined below.
Treatment of (14) with benzoyl chloride in pyridine gave (16),
which was treated sequentially with trifluoroacetic acid/water
(9 : 1) and then, again, with benzoyl chloride and pyridine at
low temperature, to furnish (17). Finally, treatment of (17)
with triflic anhydride and pyridine gave the triflate (18).
† Part VII, Aust. J. Chem., 1999, 52, 885.
10.1071/CH99031
Manuscript received 10 March 1999
© CSIRO 1999
0004-9425/99/090895

896
R. V. Stick, D. M. G. Tilbrook and S. J. Williams

897
␤-Acarbose. VIII
Alkylation of the amine (2) with the triflate (18) pro-
ceeded readily in 1,3-dimethylimidazolidin-2-one, affording
the coupled product (19) in a moderate yield (20%).Also iso-
lated from the reaction mixture was the enol ether (20), a
product of base-catalysed elimination, as an unstable oil
(18%).
Deprotection of the carba-disaccharide (19) was achieved
through a three-step sequence involving debenzoylation,
debenzylation and acetylation to afford the per-acetate (21)
in an excellent yield. In this case, the low reactivity of the
amine under the acetylation conditions was to be expected on
the basis of substantial literature precedent for these types of
compounds.2,4,13 The actual polyol (7) was also character-
ized, following processing of the per-acetate (21) under stan-
dard deacetylation conditions.
Natural, N-linked carba-sugars containing the 1,5-
anhydro D-glucitol moiety are known. Salbostatin (22), a
potent inhibitor of trehalase from porcine kidney
(Ki 0.18 µM), was isolated as a metabolite from a strain of
Streptomyces albus14 and the total synthesis has since been
described by Ogawa.15,16 In this case, the crucial imino-
linkage was achieved through aminolysis of an epoxide with
a protected valienamine.
On the basis of the satisfying synthetic sequence
described above, the task remaining was to secure a route to
the triflate (3) and to investigate the subsequent alkylations
of the 1-epivalienamine (2). The route chosen is outlined
below.
alcohol (29) was subsequently converted into the triflate (3)
in the usual manner.
With the triflate (3) in hand, it remained to investigate the
alkylation of tetra-O-benzyl-1-epivalienamine (2) with this
compound. A solution of the amine (2) and the triflate (3) in
1,3-dimethylimidazolidin-2-one was heated at 55° for 12 h,
resulting in the gradual disappearance of the triflate, as
shown by thin-layer chromatography. Purification of the
residue after workup was effected in two stages. Flash chro-
matography resolved the mixture into three fractions,
namely, the excess amine (2), a by-product, shown to be the
disaccharide (28), and an inseparable mixture of at least two
compounds (1H n.m.r.). Next, treatment of this mixture with
sodium methoxide in a mixture of tetrahydrofuran and
methanol, and subsequent purification, allowed separation of
the alkene (32) from the desired carba-tetrasaccharide (33).
The carba-tetrasaccharide (33) was isolated in a rather disap-
pointing yield of 4%. This experiment was repeated a
number of times with little variation in the yield.
The formation of the disaccharide (28) can be explained
through hydrolysis of the enol ether of the alkene (34) and
subsequent decompostion of the intermediate hemiacetal at
C5A (Scheme 1). Nevertheless, this result was surprising
given the care taken to avoid acidic conditions.
The thioglycoside (23) was prepared from 1,2:3,4-di-O-
isopropylidene- -D-galactose, according to literature
methods.17 The thioglycoside (23) was deacetylated and the
crude triol (24) was isopropylidenated to afford (25) in a
fashion similar to that used for the preparation of (10). The
resultant alcohol (25) was treated with benzoyl chloride in
pyridine to afford the benzoate (26) which was subsequently
treated with, first, trifluoroacetic acid/water (9: 1) and then
benzoyl chloride and pyridine in the usual manner to afford
the alcohol (27) in an excellent yield.
It was anticipated, in light of the ‘armed–disarmed’
concept, that the alcohol (27) would function as a glycosyl
donor in a glycosylation reaction with the alcohol (28),
affording no products of self-condensation.18 In the event, a
solution of the donor (27) and the alcohol (28) was treated
with N-iodosuccinimide and trifluoromethanesulfonic acid
to afford a difficult-to-purify mixture which was believed to
contain the disaccharide (28) and the trisaccharide (29)
(1H n.m.r.). Consequently, the alcohol (27) was converted
into the chloroacetate (30) by treatment with chloroacetic
anhydride in pyridine. In this reaction, the use of
4-(dimethylamino)pyridine as an acylation catalyst resulted
in the formation of brightly coloured impurities which were
avoided in its absence.
The glycosylation of the alcohol (28) with the donor (30)
proceeded smoothly under the conditions outlined above,
affording the trisaccharide (31) in excellent yield and purity.
The chloroacetyl group of (31) was readily removed upon
treatment with thiourea in a mixture of methanol and
dichloromethane at reflux, affording the alcohol (29). The
The carba-tetrasaccharide (33) was purified further by
recrystallization and, subsequently, treated with sodium
metal in liquid ammonia. Acetylation of the crude residue
then allowed the isolation of the carba-tetrasaccharide (35).
Unfortunately, this material contained a notable amount of
impurities. 1H n.m.r. spectroscopy indicated the presence of
around 10% of another, similar, compound, possibly an
-
anomer (at C1B) resulting from incomplete stereoselectivity
in the earlier glycosylation reaction. That the subsequent
intermediates appeared ‘anomerically pure’ could well have
resulted from the small amount of the diastereoisomer
present and the extensive overlap of benzylic methylene res-
onances with those of the anomeric protons. Such an expla-
nation for a similar occurrence has been suggested recently.19
Repeated recrystallization of the sample obtained as above
failed to purify the carba-tetrasaccharide (35). Eventually, it
was discovered that flash chromatography using a mixture of
dichloromethane and petrol effected a good purification of

898
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
(35). The 1H and 13C n.m.r. spectra of (35) were in agreement
with the proposed structure.
The failure of this reaction to produce even a limited quan-
tity of an alkylated amine is probably a result of the increased
bulk of the pivalic acid ester at O3A of (36) which, presum-
ably, prevents the approach of the nucleophile towards C4A
and the alternative elimination reaction occurs.
Prompted by the poor results of the coupling reaction
between (2) and (3) and the subsequent difficulties associ-
ated with the presence of impurities in the acetate (35), we
proposed a modified route to the carba-tetrasaccharide (1),
via the triflate (36). Central to this proposal was the inclusion
of pivaloyl protecting groups at O2A and O3A of the triflate.
Pivalic acid esters were proposed as they should be less elec-
tron withdrawing than benzoic acid esters and, therefore,
may increase the reactivity of a neighbouring triflate. It was
hoped that their increased steric bulk (compared to benzoic
acid esters) would allow for complete -stereoselectivity in
the planned glycosylation reaction, thus avoiding the
problem encountered above.
Finally, the small quantity of the carba-tetrasaccharide
(35) in hand was deacetylated by treatment with sodium
methoxide in methanol and the resultant polyol (1) was puri-
fied by means of gel permeation chromatography.
A full assignment of the signals in the 1H n.m.r. spectrum
of methyl -acarboside (1) was possible by the application of
a range of two-dimensional n.m.r. techniques including
1H–1H COSY, TOCSY and relay COSY (Table 1). Similar
methods have been used to assign completely the 1H n.m.r.
spectra of -adiposin-2 (44)13 and cellotriose20 in previous
work.
The route used to prepare the triflate (36) was similar to
that used for (3). The alcohol (25) was treated with pivaloyl
chloride in pyridine containing an equivalent of
4-(dimethylamino)pyridine, furnishing the pivaloate (37). In
this case, the relatively slow acylation reaction was conve-
niently accelerated by heating the reaction mixture.
Removal of the isopropylidene group from (37) was
effected in the usual manner with trifluoroacetic acid/water.
Treatment of the resultant diol (38) with pivaloyl chloride at
room temperature gave only a poor yield of the alcohol (39).
On the other hand, conversion of the diol (38) into the stan-
nylene acetal (upon treatment with dibutyltin oxide in
benzene) and, subsequently, treatment of the crude acetal
with pivaloyl chloride, gave the alcohol (39) in good yield.
Conversion of the alcohol (39) into the chloroacetate (40)
was achieved in the usual fashion by treatment with
chloroacetic anhydride.
Again, the glycosylation of the alcohol (28) with the
donor (40) was performed by using N-iodosuccinimide/tri-
fluoromethanesulfonic acid and proceeded without diffi-
culty, affording (41). Removal of the chloroacetyl group
from (41) to afford (42), and subsequent conversion of this
alcohol into the triflate (36), was accomplished in the usual
manner.
In contrast to the 13C n.m.r. spectrum of the acetate (35),
the 13C n.m.r. spectrum of the polyol (1) contained a number
of broadened signals, in particular, some of those assigned to
the 1-epivalienamine moiety. In this case, it is believed that
these effects arise from a slow inversion about the nitrogen
present in (1). Whilst inversion about nitrogen is usually a
fast process on the n.m.r. time-scale, substitution of nitrogen
with bulky or electron-withdrawing substituents has allowed
the observation of this phenomenon by n.m.r. spec-
troscopy.21,22
The carba-tetrasaccharide (1) and the carba-disaccharide
(7) have been assessed as inhibitors of a number of -glu-
cosidases and cellulases.23 Neither compound exhibited
notable inhibition against cellulases; however, both exhib-
ited strong inhibition of some -glucosidases. For example,
against the -glucosidase from Aspergillus niger, compound
(1) had Ki 6.7 µM and compound (7) had Ki 40 µM. These
inhibition studies will form part of a later publication.
Experimental
General experimental procedures have been given previously.24
Phenyl 3,4-O-Isopropylidene-1-thio- -D-galactoside (10)
Phenyl 1-thio- -D-galactopyranoside5,6 (10.0 g) and TsOH.H2O
(250 mg) were suspended in 2,2-dimethoxypropane (140 ml) and the
mixture was stirred until dissolution had occurred (5 min). The solution
was allowed to stand at room temperature for 2 days and then was neu-
tralized by the addition of Et3N (1 ml). The solvent was evaporated and
the residue dissolved in MeOH (150 ml) and water (1 ml) and AcOH
The coupling of the triflate (36) with the amine (2) was
the final goal. Again, as in the case of the triflate (3), the
reaction was slow and took around 24 h for the complete dis-
appearance of the triflate (36) (t.l.c.). Unfortunately, the only
isolable products were the alkene (43) and the alcohol (28).
Table 1. 1H n.m.r. (500 MHz, D2O) spectroscopic data for (1)
Asterisks * indicate that assignments were made by using two-dimensional (COSY) techniques
Pro-
ton
Ring
A
B
C
D
H 1
H 2
H 3
H 4
H 5
H 6
3.30, m*
5.64, br s
—
4.28, d (J1,2 7.9 Hz)
3.16, dd (J2,3 8.1 Hz)
3.22, m*
4.33, d (J1,2 7.9 Hz)
3.16, dd (J2,3 8.1 Hz)
3.45, m*
4.21, d (J1,2 8.0 Hz)
3.11, dd (J2,3 9.3 Hz)
3.45, m*
4.01, m
3.36, m*
3.30, m*
2.45–2.55, m
3.45, m*
3.45, m*
3.45, m* (J5,6 6.2 Hz)
1.23, d
3.42, m*
3.42, m* (J5,6 2.1 Hz)
3.62, m
3.62, m*
3.77, m
3.80, dd (J6,6 12.2 Hz)
—
H 7
3.91, br d
—
—
4.03, br d (J7,7 14.1 Hz)

899
␤-Acarbose. VIII
(2 ml) was added. The solution was allowed to stand at room tempera-
ture for 8 h, after which t.l.c. indicated the presence of one major com-
pound and a slightly more polar, minor compound. Et3N (2 ml) was
added and the solvent was evaporated. The residue was purified by flash
chromatography (70–90% EtOAc/petrol) to afford the diol (10) as a
clear oil (11.2 g, 97%). The 1H n.m.r. spectrum of this material was in
accordance with that given in the literature.25
(B) A solution of the iodide (12) (294 mg, 936 µmol), Bu3SnH
(302 µl, 1.12 mmol) and 2,2Ј-azobisisobutyronitrile (2 mg) in toluene
(5 ml) was heated at reflux under N2 for 45 min. The solvent was evap-
orated under reduced pressure and the residue partitioned between
MeCN and petrol. The MeCN layer was separated and washed with
petrol (5 times), and then the solvent was evaporated from the MeCN
layer. The residue was purified by flash chromatography (50–70%
EtOAc/petrol) to afford the deoxy sugar (14) as a pale yellow solid
1
(157 mg, 89%). This material was identical by H n.m.r. (200 MHz)
1,5-Anhydro-3,4-O-isopropylidene-D-galactitol (11)
spectroscopy to that prepared above.
A suspension of Raney nickel (2 g) and the diol (10) (507 mg) in
EtOH (25 ml) was heated under reflux for 1 h. The reaction mixture was
cooled and filtered through a plug of Celite (EtOH) and the filtrate
evaporated to afford a dark residue, containing some nickel. The residue
was purified by passage through a plug of silica (10% EtOH/EtOAc)
and the filtrate evaporated to afford the diol (11) as a white, crystalline
solid (300 mg, 90%). A small sample was crystallized as needles, m.p.
89–90° (EtOAc/petrol; lit.7 92–93°), [ ]D +80.4° (lit.7 +73.0°). 1H
n.m.r. (500 MHz) 1.31, 1.47, 2s, CMe2; 2.87–2.93, m, OH; 3.11, dd,
J1,1 11.4, J1,2 10.1 Hz, H 1; 3.55–3.61, m, OH; 3.70–3.78, m, H 2,5,6;
3.85, br dd, J5,6 8.3, J6,6 12.6 Hz, H 6; 3.93, dd, J1,2 5.3 Hz, H 1; 3.97, dd,
J2,3 6.9, J3,4 5.8 Hz, H 3; 4.14, dd, J4,5 2.1 Hz, H 4. 13C n.m.r.
(125.8 MHz) 26.11, 27.94, CMe2; 62.64, 67.86, C 1,6; 69.07, 73.90,
76.29, 79.24, C 2,3,4,5; 109.95, CMe2.
2,3-Di-O-acetyl-1,5-anhydro-6-deoxy-4-O-isopropyl-D-galactitol (15)
The isopropyl ether (13) (61 mg, 321 µmol) was treated with pyri-
dine (2 ml) and Ac2O (1 ml) at room temperature overnight under N2.
The solvent was evaporated with the aid of toluene to afford a yellow
oil which was purified by flash chromatography (10–30%
EtOAc/petrol) to afford the acetate (15) as a white, crystalline solid
(86 mg, 98%). A portion of this was recrystallized as needles, m.p.
84.5–85.5° (petrol), [ ]D +114° (Found: C, 56.9; H, 8.0. C13H22O6
requires C, 56.9; H, 8.1%). 1H n.m.r. (500 MHz) 1.11, 1.19, 2d, J 6.1,
6.1 Hz, CHMe2; 1.21, d, J5,6 6.4 Hz, 3H, H 6; 1.98, 2.05, 2s, 6H, Ac;
3.16, dd, J1,1 10.9, J1,2 10.4 Hz, H1; 3.51, dq, J4,5 1.0 Hz, H5; 3.56,
septet, CHMe2; 3.61, dd, J3,4 3.1 Hz, H4; 4.06, dd, J1,2 5.6 Hz, H1; 4.89,
dd, J2,3 10.2 Hz, H3; 5.24, ddd, H2. 13C n.m.r. (125.8 MHz) 16.91,
C 6; 20.74, 20.87, 2C, COMe; 22.21, 22.66, CHMe2; 67.01, C 1; 67.14,
74.11, 74.74, 74.80, 75.87, C 2,3,4,5, CHMe2; 169.88, 170.51, 2C, CO.
1,5-Anhydro-6-deoxy-6-iodo-3,4-O-isopropylidene-D-galactitol (12)
Iodine (1.52 g, 6.00 mmol) was added to a solution of imidazole
(680 mg, 10 mmol), Ph3P (1.57 g, 6.00 mmol) and the diol (11) (816 mg,
4.00 mmol) in toluene (25 ml) and the mixture was stirred at 90° under
N2 for 8 h. MeOH (1 ml) was added and the mixture was stirred
overnight. The organic layer was washed with water and dried. The
solvent was evaporated and the residue purified by flash chromatogra-
phy (50–70% EtOAc/petrol) to afford the iodide (12) as white crystals
(1.07 g, 85%). A small sample was recrystallized to give needles, m.p.
110–112° (Et2O/petrol), [ ]D +37.1° (Found: C, 34.4; H, 4.7; I, 40.2.
1,5-Anhydro-2-O-benzoyl-6-deoxy-3,4-O-isopropylidene-
D-galactitol (16)
A solution of BzCl (210 µl, 1.80 mmol), the deoxy sugar (14)
(284 mg, 1.51 mmol) and pyridine (360 µl, 4.5 mmol) in dry CH2Cl2
(5 ml) was allowed to stand overnight under N2, firstly at 0° (1 h) and
then at room temperature. MeOH (0.5 ml) was added and the solution
was stirred for 5 min. The solution was diluted with CH2Cl2 and washed
with aqueous HCl (1 M), aqueous Na2CO3 (2 M) and dried. The solvent
was evaporated and the residue purified by flash chromatography
(5–15% EtOAc/petrol) to afford the benzoate (16) as a white, crys-
talline solid (408 mg, 92%). A small portion was recrystallized to give
colourless needles, m.p. 84–86° (Et2O/petrol), [ ]D +110.7° (Found: C,
65.8; H, 6.8. C16H20O5 requires C, 65.7; H, 6.9%). 1H n.m.r. (500 MHz)
1.38, 1.59, 2s, CMe2; 1.40, d, J5,6 6.6 Hz, 3H, H 6; 3.28, dd, J1,1 11.4,
1
C9H15IO4 requires C, 34.4; H, 4.8; I, 40.4%). H n.m.r. (500 MHz)
1.36, 1.51, 2s, CMe2; 2.46, d, J2,OH 3.8 Hz, OH; 3.18, dd, J1,1 11.5, J1,2
9.8 Hz, H 1; 3.31, dd, J5,6 7.3, J6,6 10.1 Hz, H 6; 3.36, dd, J5,6 6.8 Hz, H 6;
3.77–3.83, m, H2; 3.85, ddd, J4,5 2.2 Hz, H5; 3.98, dd, J1,2 5.2 Hz, H1;
4.01, dd, J2,3 6.5, J3,4 5.7 Hz, H 3; 4.37, dd, H 4. 13C n.m.r. (125.8 MHz)
2.15, C 6; 26.05, 27.98, CMe2; 68.14, C 1; 69.13, 73.66, 76.35, 79.05,
C 2,3,4,5; 109.84, CMe2.
J
1,2 9.6 Hz, H 1; 3.85, dq, J4,5 2.2 Hz, H5; 4.14, dd, J3,4 5.7 Hz, H4; 4.16,
dd, J1,2 5.4 Hz, H1; 4.32, dd, J2,3 7.0 Hz, H3; 5.22, ddd, H2; 7.41–7.45,
7.54–7.58, 8.03–8.05, 3m, Ph. 13C n.m.r. (125.8 MHz) 16.96, C 6;
26.20, 27.85, CMe2; 65.55, C 1; 71.19, 72.07, 75.74, 76.32, C 2,3,4,5;
109.89, CMe2; 128.33–133.17, Ph; 165.68, CO.
1,5-Anhydro-6-deoxy-3,4-O-isopropylidene-D-galactitol (14) and
1,5-Anhydro-6-deoxy-4-O-isopropyl-D-galactitol (13)
(A) LiAlH4 (150 mg, 4.0 mmol) was added portionwise to a solution
of the iodide (12) (330 mg, 1.05 mmol) in tetrahydrofuran (10 ml) and the
resultant mixture heated at reflux under N2 for 4 h. Na2SO4·10H2O
(200 mg) was added in portions to the mixture, followed by water (1 ml).
The mixture was stirred for 1 h and then was filtered through a plug of
Celite and the solvent was evaporated from the filtrate. The residue was
purified by flash chromatography (50–100% EtOAc/petrol). First to elute
was the deoxy sugar (14) as a white, crystalline solid (27 mg, 14%), a
portion of which was recrystallized as flakey shards, m.p. 88–89°
(Et2O/petrol), [ ]D +84.9° (Found: C, 57.6; H, 8.4. C9H16O4 requires C,
57.4; H, 8.6%). 1H n.m.r. (500 MHz) 1.35, d, J5,6 6.6 Hz, 3H, H6; 1.35,
1.52, 2s, CMe2; 3.09, dd, J1,1 11.4, J1,2 10.5 Hz, H1; 3.75, dq, J4,5 2.3 Hz,
H5; 3.78, ddd, J1,2 5.4, J2,3 7.2 Hz, H2; 3.91, dd, H1; 3.94, dd, J3,4 5.6 Hz,
H3; 4.02, dd, H 4. 13C n.m.r. (125.8 MHz) 16.87, C 6; 26.27, 28.22,
CMe2; 68.15, C 1; 69.45, 72.38, 76.25, 79.63, C 2,3,4,5; 109.50, CMe2.
Next to elute was the isopropyl ether (13) as a white, crystalline solid
(123 mg, 62%), a portion of which was recrystallized as needles, m.p.
106–108° (Et2O/petrol), [ ]D +81.3° (Found: C, 57.1; H, 9.4. C9H18O4
requires C, 56.8; H, 9.5%). 1H n.m.r. (500 MHz) 1.18, 1.21, 2d, J 6.2,
6.1 Hz, CHMe2; 1.25, d, J5,6 6.5 Hz, 3H, H6; 2.96–3.07, br m, OH; 3.10,
dd, J1,1 11.0, J1,2 10.4, Hz, H 1; 3.43, dd, J2,3 9.4, J3,4 3.6 Hz, H3; 3.46, dq,
1,5-Anhydro-2,3-di-O-benzoyl-6-deoxy-D-galactitol (17)
The benzoate (16) (292 mg, 1.00 mmol) was dissolved in trifluo-
roacetic acid/water (9: 1, 3 ml) and the solvent immediately evaporated
with the aid of toluene. The residue was dried under high vacuum (2 h),
during which the sample crystallized. The residue and 4-(dimethyl-
amino)pyridine (12 mg) were dissolved in dry CH2Cl2 (10 ml) and pyri-
dine (1 ml). The solution was cooled to –40° and BzCl (245 µl,
2.12 mmol) was added in portions with regular monitoring (t.l.c.) until
the starting material had nearly disappeared. MeOH (0.5 ml) was added
to the reaction mixture and the resultant solution was allowed to warm
to room temperature. Usual workup (CH2Cl2), followed by evaporation
of the solvent and flash chromatography (20–40% EtOAc/petrol),
afforded the alcohol (17) as a white solid (217 mg, 61%). A portion was
recrystallized to afford colourless shards, m.p. 131–132° (Et2O/petrol),
[ ]D +154° (Found: C, 67.5; H, 5.8. C20H20O6 requires C, 67.4; H,
5.7%). 1H n.m.r. (300 MHz) 1.35, d, J5,6 6.4 Hz, 3H, H6; 2.15–2.35,
br m, OH; 3.44, dd, J1,1 < J1,2 10.8 Hz, H 1; 3.75, dq, J4,5 0.84 Hz, H5;
4.10, br d, H4; 4.29, dd, J1,2 5.7 Hz, H1; 5.37, dd, J2,3 10.1, J3,4 3.1 Hz,
H3; 5.67, ddd, H 2; 7.32–7.53, 7.91–8.02, 2m, 10H, Ph. 13C n.m.r.
(75.5 MHz) 16.59, C 6; 67.29, 70.70, 75.04, 75.28, C 2,3,4,5; 67.41,
C 1; 128.39–133.37, Ph; 165.76, 165.98, 2C, CO.
J
4,5 1.1 Hz, H 5; 3.50, dd, H4; 3.75, septet, CHMe2; 3.78, dd, J1,2 5.4 Hz,
H2; 3.96, dd, H 1. 13C n.m.r. (125.8 MHz) 17.19, C 6; 22.50, 22.69,
CHMe2; 68.21, 74.16, 75.24, 75.71, 77.86, C 2,3,4,5, CHMe2; 69.61, C1.

900
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
1,5-Anhydro-2,3-di-O-benzoyl-6-deoxy-4-O-
matography (30–50% EtOAc/petrol plus 1% Et3N) to give the per-
acetate (21) as a white solid (44 mg, 69%) which crystallized as
needles, m.p. 145–146° (EtOH), [ ]D –84.1° (Found: C, 53.6; H, 6.1.
C25H35NO13 requires C, 53.9; H, 6.3%). 1H n.m.r. (500 MHz) 1.27, d,
trifluoromethylsulfonyl-D-galactitol (18)
Triflic anhydride (235 µl, 1.40 mmol) was added dropwise to a solu-
tion of the alcohol (17) (356 mg, 1.00 mmol) and pyridine (240 µl,
3.0 mmol) in dry CH2Cl2 (25 ml) at –60° under N2. The reaction mixture
was allowed to warm to 0°, then was quenched by the addition of satu-
rated aqueous NaHCO3 solution (2 ml) and allowed to warm to room
temperature. The organic layer was separated, washed with water and
dried. The solvent was evaporated and the residue purified by flash
chromatography (20–30% EtOAc/petrol) to afford the triflate (18) as a
light pink, crystalline solid (455 mg, 93%). A small portion was recrys-
tallized as very fine, colourless needles, m.p. 123–124° (Et2O/petrol),
[ ]D +108° (Found: C, 51.5; H, 4.0. C21H19F3O8S requires C, 51.6; H,
3.9%). 1H n.m.r. (300 MHz) 1.38, d, J5,6 6.5 Hz, 3H, H 6; 3.51, dd, J1,1
11.1, J1,2 9.9 Hz, H 1; 3.94, br q, H 5; 4.39, dd, J1,2 4.9 Hz, H 1; 5.26, d,
J
5,6 6.1 Hz, 3H, H6; 2.00, 2.01, 2.03, 2.05, 2.05, 2.09, 6s, 18H,Ac; 2.40,
dd, J3,4 < J4,5 9.7 Hz, H4; 3.10–3.18, m, H5; 3.22, dd, J1,1 11.1, J1,2 10.4
Hz, H 1; 3.39, br d, J1Ј,6Ј 7.8 Hz, H1Ј; 4.00, dd, J1,2 5.5 Hz, H 1; 4.35,
br d, J7Ј,7Ј 13.0 Hz, H7Ј; 4.66, br d, H7Ј; 4.85, br dd, J2,3 < J3,4 9.7 Hz,
H3; 4.93, ddd, H 2; 4.97, br dd, J5Ј,6Ј 10.6 Hz, H6Ј; 5.23, dd, J4Ј,5Ј 7.7
Hz, H5Ј; 5.67, br d, H4Ј; 5.84, br s, H 2Ј. 13C n.m.r. (125.8 MHz)
17.94, C 6; 20.62, 20.71, 20.76, 20.84, 6C, COMe; 58.24, C 4; 62.39,
69.85, 70.18, 72.33, 72.62, 75.64, 78.69, C 2,3,5,1Ј,4Ј,5Ј,6Ј; 62.97,
C 7Ј; 66.58, C 1; 129.57, C 2Ј; 130.95, C 3Ј; 169.96, 170.02, 170.16,
170.31, 171.31, 6C, CO.
1,5-Anhydro-4,6-dideoxy-4-[(1 R,4 R,5 S,6 S)-4,5,6-trihydroxy-3-
J
3,4 2.8 Hz, H 4; 5.58, dd, J2,3 10.3 Hz, H3; 5.64, ddd, H 2; 7.32–7.57,
7.88–8.08, 2m, 10H, Ph. 13C n.m.r. (75.5 MHz) 16.80, C 6; 66.38,
71.68, 73.26, 85.78, C 2,3,4,5; 67.50, C 1; 118.36, q, JC,F 319 Hz, CF3;
128.47–133.74, Ph; 165.36, 165.86, 2C, CO.
(hydroxymethyl)cyclohex-2-enyl]amino-D-glucitol (7)
A solution of the per-acetate (21) (13 mg) in dry MeOH (3 ml) was
treated with a small piece of sodium metal at room temperature for 2 h.
The solution was treated with resin (IR-50, H+ form) until it became
neutral, then the solution was filtered and evaporated. The residue was
purified by gel permeation chromatography (Sephadex LH-20,
120 2.6 cm, MeOH) to afford the polyol (7) as a clear oil (6.7 mg,
94%), [ ]D –267° (H2O). 1H n.m.r. (300 MHz, D2O) 1.19, d, J5,6 6.2
Hz, 3H, H 6; 2.30, t, J3,4 < J4,5 9.6 Hz, H 4; 3.11, t, J1,1 < J1,2 11.0 Hz,
H 1; 3.15, t, J2,3 < J3,4 9.5 Hz, H 3; 3.19–3.32, m, H 5,1Ј,6Ј; 3.35–3.53,
m, H 2,5Ј; 3.79, dd, J1,2 5.5 Hz, H 1; 3.92, br d, J7Ј,7Ј 13.9 Hz, H 7Ј;
4.01–4.11, m, H 4Ј,7Ј; 5.67, br s, H 2Ј. 13C n.m.r. (75.8 MHz, D2O)
18.16, C 6; 59.84, 62.98, 70.34, 71.91, 74.38, 76.17, 76.60, 77.88,
C 2,3,4,5,1Ј,4Ј,5Ј,6Ј; 61.66, C 7Ј; 69.04, C 1; 124.44, C 2Ј; 137.75,
C 3Ј.
1,5-Anhydro-2,3-di-O-benzoyl-4,6-dideoxy-4-[(1 R,4 R,5 S,6 S)-4,5,6-
tribenzyloxy-3-(benzyloxymethyl)cyclohex-2-enyl]amino-D-
glucitol (19) and 1,5-Anhydro-2,3-di-O-benzoyl-4,6-dideoxy-L-
threo-hex-4-enitol (20)
A solution of the triflate (18) (244 mg, 0.500 mmol) and the amine
(2) (670 mg, 1.25 mmol) in 1,3-dimethylimidazolidin-2-one (1 ml) was
heated at 50° under N2 for 20 h, during which time a thick precipitate
formed. The mixture was diluted with EtOAc and washed with water,
then brine and dried. The solvent was evaporated and the residue puri-
fied by flash chromatography (5–20% EtOAc/petrol plus 1% Et3N, then
50 : 40 : 5: 1 EtOAc/toluene/EtOH/Et3N) to afford, first, the enol ether
(20) as a pale yellow oil (31 mg, 18%), [ ]D +237°. 1H n.m.r.
(500 MHz) 1.89, s, 3H, H 6; 4.24, br d, J1,1 12.3 Hz, H 1; 4.43, br d,
H1; 4.96, d, J3,4 5.0 Hz, H 3; 5.32–5.34, m, H 2; 5.38–5.42, m, H 4;
7.43–7.61, 8.03–8.07, 2m, 10H, Ph. 13C n.m.r. (125.8 MHz) 20.08,
C 6; 64.16, C 1; 65.39, 67.22, C 2,3; 93.00, C 4; 128.37–133.33, Ph;
156.51, C 5; 165.47, 2C, CO.
Phenyl 6-Deoxy-3,4-O-isopropylidene-1-thio- -D-galactoside (25)
A small piece of sodium metal was added to a suspension of phenyl
2,3,4-tri-O-acetyl-6-deoxy-1-thio- -D-galactoside (23)17 (5.25 g) in dry
MeOH (50 ml) and the mixture stirred overnight. The resultant solution
was neutralized by the addition of resin (Dowex-50, H+ form) and the
solvent was evaporated. The residue was treated with 2,2-
dimethoxypropane (25 ml) and TsOH·H2O (100 mg) at room tempera-
ture and the solution was allowed to stand at room temperature for 4 h.
The solution was quenched by the addition of Et3N (1 ml) and the
solvent was evaporated. The residue was purified by flash chromatog-
raphy (10–30% EtOAc/petrol plus 1% Et3N) to afford the alcohol (25)
as an oil which crystallized (3.10 g, 76%). Recrystallization afforded
needles, m.p. 82–83° (Et2O/petrol), [ ]D +7.6° (Found: C, 60.9; H, 6.8.
Next to elute was the D-glucitol (19) as a yellow oil (89 mg, 20%)
which crystallized as needles, m.p. 138–139° (CH2Cl2/Pri2O), [ ]D
–31.1° (Found: C, 75.7; H, 6.5. C55H55NO9 requires C, 75.6; H, 6.3%).
1H n.m.r. (500 MHz)† 1.42, d, J5,6 6.1 Hz, 3H, H6; 2.67, dd, J3,4 < J4,5
9.5 Hz, H4; 3.25, d, J7Ј,7Ј 11.4 Hz, H7Ј; 3.28–3.36, m, H 5,1Ј,6Ј; 3.42,
t, J1,1 < J1,2 10.1 Hz, H 1; 3.72–4.93, m, 8H, CH2Ph; 3.73–3.76, m, H 5Ј;
4.07, br d, H 7Ј; 4.12, br d, J4Ј,5Ј 7.4 Hz, H 4Ј; 4.26, dd, J1,2 5.1 Hz, H 1;
5.29–5.36, m, H 2,3; 5.62, br s, H2Ј; 7.12–7.48, 7.88–8.07, 2m, 10H,
Ph. 13C n.m.r. (125.8 MHz) 18.52, C 6; 60.42, C 1Ј; 62.81, C 4; 66.76,
C 1; 70.67, C 7Ј; 70.85, 75.95, C 2,3; 71.60, 74.58, 75.08, 75.86, 4C,
CH2Ph; 79.40, 79.46, C 5,4Ј; 83.18, C 6Ј; 84.64, C 5Ј; 127.37–138.61,
Ph; 133.37, C 2Ј; 134.89, C 3Ј; 165.64, 166.79, 2C, CO. High-resolu-
1
C15H20O4S requires C, 60.8; H, 6.8%). H n.m.r. (300 MHz) 1.34,
1.42, 2s, CMe2; 1.42, d, J5,6 6.6 Hz, 3H, H6; 2.64, d, J2,OH 2.5 Hz, OH;
3.54, ddd, J1,2 10.2, J2,3 6.4 Hz, H2; 3.87, dq, J4,5 2.0 Hz, H5;
4.01–4.08, m, H3,4; 4.42, d, H1; 7.26–7.33, 7.52–7.58, 2m, Ph. 13C
n.m.r. (75.5 MHz) 16.88, C 6; 26.29, 28.05, CMe2; 71.21, 72.69,
76.23, 79.04, C 2,3,4,5; 87.73, C 1; 109.79, CMe2; 127.92–132.56, Ph.
+•
tion mass spectrum (f.a.b.) m/z 874.3896 [C55H56NO9 (M+H)
requires 874.3955].
Finally, a large amount of the amine (2) was recovered (485 mg).
Phenyl 2-O-Benzoyl-6-deoxy-3,4-O-isopropylidene-1-thio- -D-
2,3-Di-O-acetyl-1,5-anhydro-4,6-dideoxy-4-[(1 R,4 R,5 S,6 S)-4,5,6-
galactoside (26)
triacetoxy-3-(acetoxymethyl)cyclohex-2-enyl]amino-D-glucitol (21)
BzCl (0.50 ml, 4.3 mmol) was added dropwise to a solution of the
alcohol (25) (1.16 g, 3.91 mmol) and pyridine (1 ml) in dry CH2Cl2
(25 ml) at room temperature under N2. The solution was left for 1 h,
then 4-(dimethylamino)pyridine (10 mg) was added and the solution
allowed to stand for a further 4 h. MeOH (1 ml) was added and the solu-
tion was allowed to stand for 5 min. Usual workup (CH2Cl2), omitting
the brine wash, followed by flash chromatography of the residue
(5–20% EtOAc/petrol plus 1% Et3N) afforded the benzoate (26) as an
oil (1.39 g, 89%) which crystallized. Recrystallization gave fine
needles, m.p. 110–111° (Et2O/petrol), [ ]D +60.5° (Found: C, 66.0; H,
6.1. C22H24O5S requires C, 66.0; H, 6.0%). 1H n.m.r. (500 MHz) 1.36,
1.59, 2s, CMe2; 1.48, d, J5,6 6.6 Hz, 3H, H6; 3.96, dq, J4,5 2.1 Hz, H5;
A solution of the D-glucitol (19) (100 mg) in dry tetrahydrofu-
ran/MeOH (1:1, 4 ml) was treated with a small piece of sodium metal.
The solution was left to stand at room temperature for 2 h. The solvent
was evaporated and the residue was suspended in dry tetrahydrofuran
(5 ml). Upon the addition of liquid ammonia (20 ml), the solid material
went into solution. Small pieces of sodium metal were added until the
mixture went blue and remained so for 2 h, then NH4OAc (0.1 g) was
added and the ammonia allowed to evaporate under a flow of nitrogen.
The residue was treated withAc2O (2 ml) and pyridine (5 ml) overnight.
The solvent was evaporated and the residue dissolved in EtOAc and
washed successively with saturated aqueous NaHCO3 and brine, dried
and the solvent evaporated. The residue was purified by flash chro-
† Primes refer to protons residing on the cyclohexene moiety.

901
␤-Acarbose. VIII
dd, J6,6 10.9 Hz, H 6B; 3.53–3.59, m, H6B,3C; 3.56, s, OMe; 3.61, dq, J4,5
0.6 Hz, H5A; 3.65, dd, J6,6 10.7 Hz, H6C; 3.84, dd, H 6C; 3.92, dd, J3,4
9.6 Hz, H 4C; 4.05, 4.10, ABq, J 14.7 Hz, ClCH2; 4.10, dd, J3,4 8.6 Hz,
H4B; 4.13–5.13, m, CH2Ph; 4.27, d, H1C; 4.31, d, J1,2 7.5 Hz, H1B;
4.82, d, J1,2 8.0 Hz, H1A; 5.24, dd, J2,3 10.5, J3,4 3.5 Hz, H3A; 5.43, dd,
H4A; 5.61, dd, H 2A; 7.12–7.62, 7.88–7.94, 2m, Ph. 13C n.m.r.
(125.8 MHz) 16.02, C 6A; 40.35, ClCH2; 57.00, OMe; 67.72, 67.82,
C 6B,6C; 68.89, C 5A; 69.95, C 2A; 71.84, C 3A; 72.51, C 4A; 73.11,
73.16, 74.81, 74.92, 75.24, 6C, CH2Ph; 74.22, C 5B; 74.79, C 5C; 75.71,
C 4B; 76.75, C 4C; 81.53, C 2C; 81.89, 82.72, 82.78, C (2,3)B,3C; 99.56,
C 1A; 102.29, C 1B; 104.58, C 1C; 127.37–139.11, Ph; 165.06, 165.40,
166.94, 3C, CO.
4.13, dd, J3,4 5.3 Hz, H 4; 4.33, dd, J2,3 7.2 Hz, H 3; 4.76, d, J1,2 10.1 Hz,
H1; 5.27, dd, H2; 7.24–7.59, 8.04–8.08, 2m, 10H, Ph. 13C n.m.r.
(125.8 MHz) 16.90, C 6; 26.36, 27.71, CMe2; 72.00, 72.62, 76.38,
77.31, C 2,3,4,5; 85.71, C 1; 110.26, CMe2; 127.63–133.47, Ph; 165.34,
CO.
Phenyl 2,3-Di-O-benzoyl-6-deoxy-1-thio- -D-galactopyranoside (27)
The benzoate (26) (2.40 g, 6.00 mmol) was treated with trifluo-
roacetic/water (10 ml, 9: 1) at room temperature and the solvent evap-
orated with the aid of toluene. The residue was dried under high vacuum
(2 h), during which time the sample crystallized. The residue and 4-
(dimethylamino)pyridine (73 mg, 0.60 mmol) were dissolved in dry
CH2Cl2 (150 ml) and pyridine (2 ml). The solution was cooled to –60°
and BzCl (1.0 ml, 8.6 ml) was added dropwise. The solution was
allowed to warm to –50°, whereupon t.l.c. indicated the consumption of
the starting material. MeOH (1 ml) was added to the reaction mixture
and the resultant solution was allowed to warm to 0°. Usual workup
(CH2Cl2) afforded a residue which was purified by flash chromatogra-
phy (10–40% EtOAc/petrol) to give the alcohol (27) as a white solid
(2.53 g, 91%). A portion was recrystallized to afford small chunky crys-
tals, m.p. 178–180° (CH2Cl2/petrol), [ ]D +123.0° (Found: C, 67.3; H,
5.1. C26H24O6S requires C, 67.2; H, 5.2%). 1H n.m.r. (300 MHz) 1.44,
d, J5,6 6.5 Hz, 3H, H6; 3.93, dq, J4,5 0.9 Hz, H 5; 4.10–4.15, m, H4;
4.91, d, J1,2 10.0 Hz, H1; 5.32, dd, J2,3 10.0, J3,4 10.0 Hz, H 3; 5.71, dd,
H2; 7.25–7.56, 7.91–8.05, 2m, 15H, Ph. 13C n.m.r. (75.5 MHz) 16.55,
C 6; 67.80, 70.23, 74.84, 75.95, C 2,3,4,5; 86.39, C 1; 128.07–133.39,
Ph; 165.29, 165.86, 2C, CO.
Methyl O-(2,3-Di-O-benzoyl-6-deoxy- -D-galactopyranosyl)-(1 4)-
O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-2,3,6-tri-O-benzyl- -D-
glucoside (29)
A solution of the chloroacetate (31) (786 mg, 592 µmol), thiourea
(450 mg, 5.92 mmol) and 2,6-lutidine (69 µl, 590 µmol) in
CH2Cl2/MeOH (20 ml, 1:1) was heated under reflux overnight. The
solvent was evaporated and the residue partitioned between CH2Cl2 and
water. The organic phase was separated and washed with aqueous HCl
(1 M), saturated aqueous NaHCO and dried. The solvent was evapo-
3
rated and the residue purified by flash chromatography (5–15%
EtOAc/toluene) to give the alcohol (29) as a syrup (727 mg, 98%), [ ]D
+38.4° (Found: C, 72.0; H, 6.2. C75H78O17 requires C, 72.0; H, 6.3%).
1H n.m.r. (500 MHz) 1.26, d, J5,6 6.5 Hz, 3H, H 6A; 2.03, d, J4,OH 6.6
Hz, OH; 2.94, ddd, J4,5 9.8, J5,6 1.5, 3.0 Hz, H 5B; 3.32, ddd, J4,5 9.8, J5,6
1.9, 3.6 Hz, H5C; 3.34–3.42, m, H(2,3)B,2C; 3.49, dd, J6,6 11.0 Hz, H 6B;
3.54–3.61, m, H 5A,6B,3C; 3.58, s, OMe; 3.67, dd, J6,6 10.7 Hz, H6C;
3.86, dd, H 6C; 3.95, dd, J3,4 9.0 Hz, H4C; 3.99, dd, J3,4 3.3 Hz, H4A;
4.11, dd, J3,4 8.8 Hz, H4B; 4.18–5.13, m, CH2Ph; 4.31, d, J1,2 7.8 Hz,
H1C; 4.33, d, J1,2 7.5 Hz, H1B; 4.82, d, J1,2 8.0 Hz, H1A; 5.12, dd, J2,3
10.4 Hz, H3A; 5.68, dd, H 2A; 7.15–7.61, 7.92–8.04, 2m, Ph. 13C n.m.r.
(125.8 MHz) 15.95, C 6A; 56.97, OMe; 67.73, C 6B; 67.79, C 6C;
70.01, 70.06, C (2,4)A; 70.30, C 5A; 73.05, 73.14, 74.74, 74.87, 75.33,
Phenyl 2,3-Di-O-benzoyl-4-O-chloroacetyl-6-deoxy-1-thio- -D-
galactoside (30)
A solution of the alcohol (27) (502 mg, 1.08 mmol), chloroacetic
anhydride (256 mg, 1.50 mmol) and pyridine (1 ml) in CH2Cl2 (25 ml)
was allowed to stand at room temperature for 4 h. Water (1 ml) was
added and the mixture stirred for 5 min. Usual workup (CH2Cl2)
afforded a yellow, crystalline solid which was passed through a plug of
silica (20–40% EtOAc/petrol) to give a white, crystalline solid which
was recrystallized to give the chloroacetate (30) as a white powder
(2.64 g, 90%), m.p. 114–115° (Et2O/petrol), [ ]D +92.5° (Found: C,
62.2; H, 4.8. C28H25ClO7S requires C, 62.2; H, 4.7%). 1H n.m.r.
(300 MHz) 1.34, d, J5,6 6.4 Hz, 3H, H 6; 4.06, dq, J4,5 0.9 Hz, H 5;
4.13, s, ClCH2; 4.96, d, J1,2 9.9 Hz, H 1; 5.48, dd, J2,3 9.9, J3,4 3.2 Hz,
H3; 5.56, dd, H 4; 5.66, dd, H 2; 7.29–7.56, 7.85–8.00, 2m, 15H, Ph.
13C n.m.r. (75.5 MHz) 16.57, C 6; 40.36, ClCH2; 67.61, 72.61, 73.02,
73.20, C 2,3,4,5; 86.36, C 1; 128.21–133.45, Ph; 165.17, 165.51,
166.93, 3C, CO.
6C, CH Ph; 74.31, C 5B; 74.76, C 5C; 74.82, C 3A; 75.69, C 4B; 76.66,
2
C 4C; 81.50, 81.96, 82.87, C (2,3)B,2C; 82.73, C 3C; 99.80, C 1A; 102.24,
C 1B; 104.54, C 1C; 127.52–138.62, Ph; 165.11, 165.75, 2C, CO.
Methyl O-(2,3-Di-O-benzoyl-6-deoxy-4-O-trifluoromethylsulfonyl- -
D-galactosyl)-(1 4)-O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-
2,3,6-tri-O-benzyl- -D-glucoside (3)
Triflic anhydride (150 µl, 890 µmol) was added dropwise to a solu-
tion of the alcohol (29) (558 mg, 446 µmol) and pyridine (180 µl,
2.2 mmol) in dry CH2Cl2 (15 ml) at –60° under N2. The reaction mixture
was allowed to warm to 10°, and then was quenched by the addition of
saturated aqueous NaHCO3 solution (2 ml). The organic layer was sep-
arated and washed with water and dried. The solvent was evaporated
and the residue purified by flash chromatography (10–30%
EtOAc/petrol) to afford the triflate (3) as a colourless foam (535 mg,
87%), [ ]D +18.8° (Found: C, 65.7; H, 6.1. C76H77F3O19S requires C,
Methyl O-(2,3-Di-O-benzoyl-4-O-chloroacetyl-6-deoxy- -D-
galactosyl)-(1 4)-O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-
2,3,6-tri-O-benzyl- -D-glucoside (31)
A solution of N-iodosuccinimide (819 mg, 3.64 mmol) and TfOH
(100 µl) in dry dichloroethane/Et O (16 ml, 1:1) at 0° was added to a
2
1
66.0; H, 5.6%). H n.m.r. (500 MHz) 1.24, d, J5,6 6.5 Hz, 3H, H6A;
solution of methyl 2,3,6,2Ј,3Ј,6Ј-hexa-O-benzyl- -cellobioside (28)26
(1.81 g, 2.02 mmol) and the chloroacetate (30) (1.53 g, 2.83 mmol) in
dry dichloroethane (12 ml) at 0° under N2. The solution was allowed to
warm to room temperature and was left to stand for 30 min. Water
(100 µl) was added and the mixture was stirred for 5 min. The mixture
was quenched by the addition of saturated aqueous NaHCO2 (1 ml) and
aqueous Na2S2O3 (5 ml, 0.5 M) and the resultant mixture was stirred for
5 min. The organic phase was separated, dried and the solvent was
evaporated. The residue was purified by flash chromatography (5–10%
EtOAc/toluene) to afford the chloroacetate (31) as a foam (2.03 g,
76%), [ ]D +28.3° (Found: C, 69.4; H, 5.9. C77H79ClO18 requires C,
69.6; H, 6.0%). 1H n.m.r. (500 MHz) 1.16, J5,6 6.5 Hz, 3H, H6A; 2.91,
ddd, J4,5 9.8, J5,61.4, 2.9 Hz, H 5B; 3.30, ddd, J4,5 9.9, J5,6 1.9, 3.6 Hz,
H5C; 3.31–3.36, m, H (2,3)B; 3.38, dd, J1,2 7.8, J2,3 9.2 Hz, H2C; 3.48,
2.86, ddd, J4,5 9.9, J5,6 1.3, 2.5 Hz, H 5B; 3.27, ddd, J4,5 9.8, J5,6 1.8, 3.4
Hz, H 5C; 3.31–3.35, m, H(2,3)B; 3.37, dd, J1,2 7.8, J2,3 9.1 Hz, H2C;
3.45, dd, J6,611.0 Hz, H 6B; 3.54, dd, J3,4 9.0 Hz, H 3C; 3.54–3.57, m,
H6B; 3.55, s, OMe; 3.60, br q, H5A; 3.62, dd, J6,6 10.7 Hz, H6C; 3.83,
dd, H6C; 3.91, dd, H4C; 4.03–4.07, m, H4B; 4.11–5.10, m, CH2Ph;
4.26, d, H 1C; 4.27–4.28, m, H 1B; 4.80, d, J1,2 8.1 Hz, H1A; 5.11, br d,
J
3,4 3.1 Hz, H4A; 5.24, dd, J2,3 10.6 Hz, H3A; 5.65, dd, H 2A; 7.11–7.61,
7.86–8.02, 2m, Ph. 13C n.m.r. (125.8 MHz) 16.25, C 6A; 57.03, OMe;
67.67, C 6C; 67.79, C 6B; 68.68, C 5A; 68.98, C 2A; 71.11, C 3A; 73.13,
73.20, 74.87, 74.91, 75.60, 6C, CH2Ph; 74.14, C 5B; 74.76, C 5C; 76.13,
C 4B; 76.74, C 4C; 81.54, C 2C; 82.02, 82.51, C (2,3)B; 82.78, C 3C;
85.11, C 4A; 99.73, C 1A; 102.28, C 1B; 104.61, C 1C; 118.29, q, JC,F 320
Hz, CF3; 127.41–139.34, Ph; 164.69, 165.65, 2C, CO.

902
R. V. Stick, D. M. G. Tilbrook and S. J. Williams
Methyl O-{4,6-Dideoxy-4-[(1R,4R,5S,6S)-4,5,6-tribenzyloxy-3-
(benzyloxymethyl)cyclohex-2-enyl]amino- -D-glucosyl}-(1 4)-O-
(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-2,3,6-tri-O-benzyl- -D-
glucoside (33) and Methyl O-(4,6-Dideoxy- -L-threo-hex-4-enosyl)-
(1 4)-O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-2,3,6-tri-O-benzyl-
-D-glucoside (32)
mixture of compounds as a colourless glass (24 mg) which crystallized
1
as needles, m.p. 124–126° (EtOH). This material was shown by H
n.m.r. (500 MHz) spectroscopy to be impure.
(B) The accumulated residues from several reactions of the type
described in (A) were purified by flash chromatography (30–35%
CH2Cl2/petrol) to give the per-acetate (35) as a fine powder, [ ]D
–49.1° (Found: C, 51.6; H, 5.8. C50H69NO30 requires C, 51.6; H, 6.0%).
1H n.m.r. (500 MHz) 1.29, d, J5,6 6.2 Hz, 3H, H 6B; 1.96, 1.99, 2.00,
2.02, 2.03, 2.04, 2.04, 2.12, 2.13, 9s, 36H, Ac; 2.43, t, J3,4 < J4,5 9.7 Hz,
H4B; 3.14, dq, H5B; 3.30–3.37, m, H 1A; 3.52–3.58, m, H 5C,5D; 3.73,
t, J3,4 < J4,5 9.1 Hz, 3.75, t, J3,4 < J4,5 9.4 Hz, H4C,4D; 4.05–4.10, m,
H6C,6D; 4.05–4.10, m, H6C,6D; 4.32, d, J1,2 7.6 Hz, H 1B; 4.45, d, J1,2
7.9 Hz, H1C; 4.34, br d, J7,7 13.5 Hz, H7A; 4.36, d, J1,2 7.9 Hz, H 1D;
4.37, dd, J5,6 1.8, J6,6 12.0 Hz, 4.52, dd, J5,6 2.1, J6,6 12.0 Hz, H6C,6D;
4.75, t, J2,3 < J3,4 9.7 Hz, H 3B; 4.80, dd, H2B; 4.84, dd, J2,3 9.1 Hz, 4.87,
dd, J2,3 9.4 Hz, H2C,2D; 4.94, dd, J1,6 8.7, J5,6 10.5 Hz, H6A; 5.09, t, J2,3
< J3,4 9.1 Hz, 5.15, t, J2,3 < J3,4 9.4 Hz, H 3C,3D; 5.21, dd, J4,5 7.6 Hz,
H5A; 5.65, br d, H4A; 5.79, br s, H 2A. 13C n.m.r. (125.8 MHz) 17.80,
C 6B; 20.51, 20.61, 20.65, 20.70, 20.78, 20.87, 20.98, 12C, COMe;
57.00, OMe; 58.21, C 1A; 61.71, 62.20, C 6C,6D; 61.91, C 4B; 62.89,
C 7A; 70.05, C 4A; 71.54, 71.79, 72.22, 72.40, 72.51, 72.64, 72.73,
73.27, C (5,6)A,2B,(2,3,5)C,(2,3,5)D; 74.09, C 5B; 74.65, C 3B; 76.08,
76.35, C 4C,4D; 100.47, 100.53, C 1B,1C; 101.41, C 1D; 129.04, C 2A;
131.19, C 3A; 169.33, 169.44, 169.64, 169.70, 169.76, 169.92, 169.99,
170.10, 170.22, 170.26, 170.31, 171.14, 12C, CO.
A solution of the amine (2) (387 mg, 723 µmol) and the triflate (3)
(400 mg, 289 µmol) in 1,3-dimethylimidazolidin-2-one (1 ml) was
heated at 60° under N2 overnight. The solution was diluted with EtOAc
and washed with water, then dried and the solvent evaporated to give
an orange oil. This oil was purified by flash chromatography
(5–20% EtOAc/toluene plus 1% Et3N, then 50 : 44: 5: 1
EtOAc/toluene/EtOH/Et3N) to give, first, another orange oil (200 mg),
shown to be a mixture of compounds, and, second, unreacted amine (2)
(348 mg). The orange oil was further purified by flash chromatography
(30–35% Et2O/petrol plus 1% Et3N) to give, first, a light brown oil
(100 mg), still being a mixture of compounds, and, next, the disaccha-
ride alcohol (28) (96 mg, 37%). The light brown oil was then dissolved
in dry MeOH/tetrahydrofuran (4 ml) and treated with a small piece of
sodium metal overnight under N2. The solvent was evaporated and the
residue purified by flash chromatography (20–50% EtOAc/toluene plus
1% Et3N) to afford, firstly, the carba-tetrasaccharide (33) (20 mg) as a
light brown oil which crystallized as needles, m.p. 129–132°, [ ]D
–21.5° (Found: C, 73.8; H, 6.8. C96H105NO18 requires C, 73.9; H, 6.8%).
1H n.m.r. (500 MHz) 1.17, d, J5,6 6.2 Hz, 3H, H 6B; 2.12, t, J3,4 < J4,5
9.6 Hz, H 4B; 2.84, dq, H 5B; 2.89–2.94, m, H 3B; 3.21–3.27, 3.30–3.36,
2m, H (1,6)A,2B,5C,5D; 3.39, 3.42, 2dd, J1,2 7.8, J2,3 9.0 Hz, H2C,2D;
3.54, 3.57, 2t, J2,3 < J3,4 9.0 Hz, H 3C,3D; 3.56, s, OMe; 3.63, 3.79, 2dd,
J5,6 2.2, 3.0, J6,6 11.7 Hz, 3.72, 3.82, 2dd, J5,6 1.2, 1.5, J6,6 11.2 Hz,
H6C,6D; 3.78–3.85, m, H 5A; 3.86, br d, J7,7 11.8 Hz, H7A; 4.01, 4.04,
2t, J3,4 < J4,5 9.0 Hz, H 4C,4D; 4.23, br d, H 7A; 4.28–4.31, m, H 4A; 4.29,
4.52, 2d, H 1C,1D; 4.40–5.03, m, CH2Ph; 4.54, d, J1,2 7.7 Hz, H1B; 5.72,
br s, H 2A; 7.15–7.35, m, Ph. 13C n.m.r. (125.8 MHz) 18.45, C 6B;
57.02, OMe; 58.55, C 1A; 62.48, C 4B; 68.07, 68.51, C 6C,6D; 70.36,
C 7A; 72.36, 73.12, 73.31, 74.55, 74.81, 74.99, 75.26, 75.30, 10C,
CH2Ph; 73.90, C 5B; 74.20, 74.95, C 5C,5D; 74.44, C 3B; 75.38, C 2B;
76.23, 76.97, C 4C,4D; 80.04, C 4A; 81.73, 82.57, C 2C,2D; 82.26, C 6A;
82.63, 84.06, C 3C,3D; 85.06, C 5A; 102.40, 104.65, C 1C,1D; 102.91,
C 1B; 126.96, C 2A; 127.14–139.11, m, C 3A,Ph.
Phenyl 6-Deoxy-3,4-O-isopropylidene-2-O-pivaloyl-1-thio- -D-
galactoside (37)
A solution of the alcohol (25) (4.78 g, 16.2 mmol), 4-(dimethyl-
amino)pyridine (1.97 g, 16.2 mmol) and pivaloyl chloride (6.0 ml,
49 mmol) in pyridine (100 ml) was left at room temperature overnight
under N2 and then heated at 100° for 1 h. The mixture was cooled and
then water (2 ml) was added and the mixture stirred for 5 min. The
solvent was evaporated and the residue dissolved in EtOAc and the
solution was sequentially washed with water, brine and dried. The
solvent was evaporated and the residue purified by flash chromatogra-
phy (5–30% EtOAc/petrol plus 1% Et3N) to afford the pivaloate (37) as
colourless needles (5.47 g, 89%), m.p. 131–132° (Et2O/petrol), [ ]D
+20.3° (Found: C, 63.3; H, 7.2. C20H28O5S requires C, 63.1; H, 7.4%).
1H n.m.r. (500 MHz) 1.22, s, CMe3; 1.31, 1.49, 2s, CMe2; 1.40, d, J5,6
6.6 Hz, 3H, H 6; 3.84, dq, J4,5 2.0 Hz, H5; 4.02, dd, J3,4 5.3 Hz, H4;
4.11, dd, J2,3 7.1 Hz, H 3; 4.56, d, J1,2 10.2 Hz, H 1; 4.98, dd, H2;
7.19–7.29, 7.39–7.48, 2m, Ph. 13C n.m.r. (75.5 MHz) 16.85, C 6;
26.38, 27.63, CMe2; 27.05, CMe3; 38.61, CMe3; 70.80, 72.36, 76.24,
77.26, C 2,3,4,5; 85.92, C 1; 110.02, CMe2; 127.53–133.80, Ph; 176.76,
CO.
Last to elute was the alkene (32) (30 mg, 10%) as a clear oil,
[ ]D +8.0° (Found: C, 71.4; H, 6.6. C61H68O14 requires C, 71.5; H,
6.7%). 1H n.m.r. (500 MHz)
1.48, br s, 3H, H 6A; 2.43–2.50,
2.65–2.74, 2 br s, OH; 3.15–3.19, m, H 5B; 3.31, ddd, J4,5 9.8, J5,6 1.7,
3.5 Hz, H 5C; 3.35–3.42, m, H (2,3)C; 3.41, dd, J1,2 7.8, J2,3 9.1 Hz, H2B;
3.54–3.60, m, H 3A,3B; 3.56, s, OMe; 3.60–3.65, m, 2H, H6B; 3.69, dd,
J
6,6 10.6 Hz, H6C; 3.83, dd, H 6C; 3.93–3.98, m, H 2A; 3.97, t, J3,4 < J4,5
9.1 Hz, H 4B; 4.03, t, J3,4 < J4,5 9.8 Hz, H 4C; 4.28, d, H 1B; 4.35–5.03,
m, CH2Ph; 4.46–4.48, m, H 1C; 4.62, br d, J1,2 3.8 Hz, H 1A; 5.12, br d,
J3,4 5.0 Hz, H4A; 7.18–7.36, m, 30H, Ph. 13C n.m.r. (125.8 MHz)
19.23, C 6A; 57.01, OMe; 67.38, C 2A; 67.96, C 6C; 68.84, C 6B; 71.06,
C 3A; 73.17, 73.39, 74.80, 75.05, 75.15, 6C, CH2Ph; 74.09, C 5B; 74.83,
C 5C; 76.30, C 4C; 77.00, C 4B; 81.63, C 2B; 82.59, 82.65, 82.84,
C 3B,(2,3)C; 98.51, C 1A; 100.30, C 4A; 102.21, C 1C; 104.63, C 1B;
127.25–138.59, Ph; 149.73, C 5A.
Phenyl 6-Deoxy-2,3-di-O-pivaloyl-1-thio- -D-galactopyranoside (39)
(A) The pivaloate (37) (1.30 g, 3.41 mmol) was treated with trifluo-
roacetic acid/water (3 ml, 9:1) at room temperature and the solvent
evaporated with the aid of toluene. The residue was purified by passage
through a short plug of silica (50–100% EtOAc/petrol) to afford a
white, crystalline solid. A mixture of the residue and dibutyltin oxide
(848 mg, 3.41 mmol) in benzene (25 ml) was distilled to remove water
as an azeotrope. The residual solvent was evaporated and the residue
was dissolved in dry dichloroethane (8 ml) and treated with pivaloyl
chloride (421 µl, 3.41 mmol) at room temperature for 1 h. The solvent
was evaporated and the residue was purified by flash chromatography
(10–40% EtOAc/petrol) to afford a white solid (1.44 g). This material
was taken up in CH2Cl2 and crystallized upon addition of petrol to
afford the alcohol (39) as colourless needles (1.08 g, 74%), m.p.
164–165° (Et2O/petrol), [ ]D +23.8° (Found: C, 61.9; H, 7.7.
Methyl O-{2,3-Di-O-acetyl-4,6-dideoxy-4-[(1R,4R,5S,6S)-4,5,6-
triacetoxy-3-(acetoxymethyl)cyclohex-2-enyl]amino- -D-glucosyl}-
(1 4)-O-(tri-O-acetyl- -D-glucosyl)-(1 4)-tri-O-acetyl- -D-
glucoside (35)
(A) Small pieces of sodium metal were added to a mixture of the
carba-tetrasaccharide (33) (43 mg) in liquid ammonia (20 ml) and dry
tetrahydrofuran (3 ml) until the mixture went blue and remained so for
2 h. NH4OAc (0.1 g) was added and the ammonia allowed to evaporate
under a flow of nitrogen. The residue was treated with Ac2O (3 ml) and
pyridine (5 ml) overnight. The solvent was evaporated and the residue
partitioned between CH2Cl2 and water. The organic layer was separated
and washed successively with water, then was dried and the solvent
evaporated under reduced pressure. The residue was purified by flash
chromatography (50–100% EtOAc/petrol plus 1% Et3N) to give a
1
C22H32O6S requires C, 62.2; H, 7.6%). H n.m.r. (300 MHz) 1.18,
1.20, 2s, 18H, CMe3; 1.36, d, J5,6 6.4 Hz, 3H, H6; 3.74, dq, J4,5 0.93 Hz,
H5; 3.87, dd, J3,4 3.1 Hz, H4; 4.68, d, J1,2 10.1, Hz, H1; 4.97, dd, J2,3
9.9 Hz, H 3; 5.29, dd, H 2; 7.28–7.34, 7.45–7.51, 2m, Ph. 13C n.m.r.
(75.5 MHz) 16.47, C 6; 27.06, 27.09, 6C, CMe3; 38.68, 38.86, 2C,
CMe3; 66.66, 70.12, 74.58, 4C, C 2,3,4,5; 86.75, C 1; 127.92–133.04,
Ph; 176.56, 177.55, 2C, CO.

903
␤-Acarbose. VIII
H2A; 7.14–7.44, m, Ph. 13C n.m.r. 15.87, C 6A; 27.08, 27.24, 6C,
(B) The pivaloate (37) (1.12 g, 3.19 mmol) was treated with trifluo-
roacetic acid/water (2 ml, 9:1) at room temperature and the solvent evap-
orated with the aid of toluene to afford a white crystalline solid. The
residue was dried under high vacuum and then dissolved in dry
CH2Cl2/pyridine (1:1, 50 ml). The solution was treated with 4-(dimeth-
ylamino)pyridine (389 mg, 3.19 mmol) and pivaloyl chloride (550 µl,
4.47 mmol) at 0° for 1 h, then overnight at room temperature. Water
(1 ml) was added to the reaction mixture and the resultant mixture was
stirred overnight. Usual workup (CH2Cl2) and flash chromatography
(10–40% EtOAc/petrol) of the residue afforded the alcohol (39) as a
white solid (651 mg, 48%). The 1H n.m.r. (200 MHz) spectrum of this
material was identical to that of the material prepared above.
CMe3; 38.70, 38.84, 2C, CMe3; 57.05, OMe; 67.87, 67.99, C 6B,6C;
A
A
69.31, C 2 ; 69.94, C 4 ; 70.11, 77.15, 81.62, 81.89, 82.91, 82.94,
C 5A,(2,3)B,(2,3,5)C; 73.06, 73.24, 74.84, 75.02, 75.48, 6C, CH2Ph;
73.77, C 3A; 74.31, C 4B; 74.69, C 5B; 75.48, C 4C; 98.99, C 1A; 102.64,
C 1B; 104.61, C 1C; 127.33–138.70, m, Ph; 176.56, 177.58, 2C, CO.
High-resolution mass spectrum (f.a.b.) m/z 1209.5718 [C71H85O17
+•
(M–H) requires 1209.5787].
Methyl O-(6-Deoxy-2,3-di-O-pivaloyl-4-O-trifluoromethylsulfonyl- -
D-galactosyl)-(1 4)-O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-
2,3,6-tri-O-benzyl- -D-glucoside (36)
The alcohol (42) (706 mg) was treated with triflic anhydride and
pyridine in CH2Cl2 as for the alcohol (29) above. The reaction was sub-
jected to the usual workup (CH2Cl2) to afford a pale yellow oil which
was purified by flash chromatography (10–20% EtOAc/petrol) to
furnish the triflate (36) as a colourless foam (678 mg, 87%), [ ]D –2.0°
Phenyl 4-O-Chloroacetyl-6-deoxy-2,3-di-O-pivaloyl-1-
thio- -D-galactoside (40)
A solution of the alcohol (39) (474 mg, 1.12 mmol), chloroacetic
anhydride (286 mg, 1.67 mmol) and pyridine (1 ml) in dry CH2Cl2
(10 ml) was allowed to stand at room temperature overnight. Water
(1 ml) was added and the mixture stirred for 5 min. The mixture was
subjected to the usual workup (CH2Cl2) to give a yellow oil which was
purified by flash chromatography (20–40% EtOAc/petrol) to afford the
chloroacetate (40) as a white solid (497 mg, 89%). Recrystallization
then afforded colourless needles, m.p. 130–130.5° (Et2O/petrol), [ ]D
–6.1° (Found: C, 57.6; H, 6.4. C24H33ClO7S requires C, 57.5; H, 6.6%).
1H n.m.r. (500 MHz) 1.10, 1.20, 2s, 18H, CMe3; 1.25, d, J5,6 6.4 Hz,
3H, H6; 3.88, dq, J4,5 0.95 Hz, H 5; 4.08–4.18, m, CH2Cl; 4.72, d, J1,2
9.9 Hz, H 1; 5.11, dd, J2,3 9.9, J3,4 3.3 Hz, H 3; 5.25, dd, H 2; 5.36, dd,
H4; 7.28–7.35, 7.46–7.52, 2m, Ph. 13C n.m.r. (75.5 MHz) 16.44, C 6;
26.90, 27.08, 6C, CMe3; 38.68, 38.75, 2C, CMe3; 40.42, ClCH2; 66.50,
71.98, 72.39, 72.87, C 2,3,4,5; 128.08–132.72, Ph; 166.98, COCH2Cl;
176.46, 177.21, 2C, COCMe3.
1
(Found: C, 64.3; H, 6.2. C72H85F3O19S requires C, 64.4; H, 6.4%). H
n.m.r. (300 MHz) 1.16, 1.22, 2s, 18H, CMe3; 1.18–1.22, m, 3H, H6A;
3.08–3.14, m, H5B; 3.27–3.69, H5A,(2,3,6,6)B,(2,3,5,6)C; 3.56, s, OMe;
3.87, dd, J5,6 3.6, J6,6 10.7 Hz, H6C; 3.97, dd, J3,4 < J4,5 9.3 Hz, H4C;
4.08–4.17, m, H 4B; 4.15–5.16, m, CH2Ph; 4.29, d, J1,2 7.7 Hz, H 1C;
4.37–4.41, m, 4.44, d, J1,2 8.0 Hz, H1A,1B; 4.81, dd, J2,3 10.5, J3,4 2.9
Hz, H 3A; 4.92, br d, H4A; 5.22, dd, J1,2 8.0 Hz, H2A; 7.08–7.45, m, Ph.
13C n.m.r. (75.5 MHz) 16.19, C 6A; 27.08, 27.30, 6C, CMe3; 38.74,
39.00, 2C, CMe3; 57.06, OMe; 67.78, 67.95, C 6B,6C; 68.43, 68.47,
70.70, 74.45, 74.74, 74.81, 77.18, 81.61, 81.90, 82.56, 82.90, 85.18,
C (2,3,4,5)A,(2,3,4,5)B,(2,3,4,5)C; 99.01, C 1A; 102.64, C 1B; 104.63,
C 1C; 118.34, q, JC,F 319 Hz, CF3; 127.02–139.41, Ph; 176.09, 177.99,
2C, CO. High-resolution mass spectrum (f.a.b.) m/z 1341.5278
+•
[C72H84F3O19S (M –H) requires 1341.5280].
Methyl O-(4-O-Chloroacetyl-6-deoxy-2,3-di-O-pivaloyl- -D-
galactosyl)-(1 4)-O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-
2,3,6-tri-O-benzyl- -D-glucoside (41)
Attempted Coupling of the Triflate (36) with the Amine (2)
A solution of the amine (2) (299 mg, 558 µmol) and the triflate (36)
(300 mg, 223 µmol) in 1,3-dimethylimidazolidin-2-one (2 ml) was
heated at 55° under N2 for 1 day. The solution was diluted with EtOAc
and washed with water, then dried and the solvent evaporated to give
an orange oil. This was purified by flash chromatography
(0–20% EtOAc/toluene plus 1% Et3N, then 50: 44 : 5: 1
EtOAc/toluene/EtOH/Et3N) to give, first, a yellow oil (200 mg) shown
to be a mixture of compounds and, second, a light orange oil (159 mg),
shown to consist mainly of the alcohol (28). The yellow oil was further
purified by flash chromatography (25–35% Et2O/petrol plus 1% Et3N)
to give a dark yellow oil (157 mg), shown to be mainly the alkene (43).
Partial 1H n.m.r. for (43): 1.07, 1.21, 18H, CMe3; 1.45, br s, 3H, H6A;
3.56, s, OMe; 5.04–5.07, m, H4A; 7.10–7.40, m, Ph. Partial 13C n.m.r.
for (43): 19.58, C 6A; 26.88, 27.14, 6C, CMe3; 38.57, 38.73, 2C,
CMe3; 57.02, OMe; 102.51, C 1C; 104.59, C 1B; 127.17–138.55, Ph;
152.49, C 5A; 177.03, 177.94, CO.
The chloroacetate (40) (800 mg, 892 µmol) was treated with the
alcohol (28) (800 mg, 892 µmol) as for (30) above to afford, after flash
chromatography (5–10% EtOAc/toluene), the chloroacetate (41) as a
foam (945 mg, 82%), [ ]D +1.6° (Found: C, 68.3; H, 6.9. C73H87ClO18
requires C, 68.1; H, 6.8%). 1H n.m.r. (500 MHz) 1.10, d, J5,6 6.5 Hz,
3H, H6A; 1.11, 1.13, 2s, 18H, CMe3; 3.09–3.14, m, H 5B; 3.30–3.43,
3.54–3.68, 2m, H 5A,(2,3,6,6)B,(2,3,5,6)C; 3.56, s, OMe; 3.86, dd, J5,6
3.9, J6,6 10.9 Hz, H 6C; 3.95, d, J 15.0 Hz, 1H, CH2Cl; 3.97, dd, J3,4 <˜
J
4,5 9.3 Hz, H 4C; 4.01, d, 1H, CH2Cl; 4.13, dd, J3,4 8.7, J4,5 9.8 Hz, H 4B;
4.16–5.14, m, CH2Ph; 4.28, d, J1,2 7.8 Hz, H1C; 4.41, d, J1,2 7.5 Hz,
H1A; 4.43, d, J1,2 8.0 Hz, H1A; 4.81, dd, J2,3 7.0, J3,4 3.5 Hz, H3A; 5.13,
dd, H 2A; 5.18, br d, H 4A; 7.16–7.44, m, Ph. 13C n.m.r. (125.8 MHz)
15.93, C 6A; 26.94, 27.21, 6C, CMe3; 38.70, 38.71, 2C, CMe3; 40.36,
CH2Cl; 57.04, OMe; 67.86, 67.92, C 6B,6C; 68.59, 74.84, 81.60, 81.75,
82.73, 82.92, C 5A,(2,3)B,(2,3,5)C; 69.27, C 2A; 71.04, C 3A; 72.38, C 4A;
73.08, 73.23, 74.82, 74.87, 75.01, 75.29, 6C, CH2Ph; 74.32, C 4B;
74.55, C 5B; 77.21, C 4C; 98.71, C 1A; 102.65, C 1B; 104.59, C 1C;
127.01–139.38, Ph; 167.00, COCH2Cl; 176.54, 177.19, 2C, COCMe3.
Methyl O-{4,6-Dideoxy-4-[(1R,4R,5S,6S)-4,5,6-trihydroxy-3-
(hydroxymethyl)cyclohex-2-enyl]amino- -D-glucosyl}-(1 4)-O-
-D-glucosyl-(1 4)-O- -D-glucoside, Methyl -Acarboside (1)
High-resolution mass spectrum (f.a.b.) m/z 1286.5589 [C73H87ClO18
A suspension of the acetate (35) (9 mg) in dry MeOH was treated
with a small piece of sodium metal and the mixture stirred (2 h). The
solution was neutralized with resin (Dowex-50, H+ form), filtered and
the solvent evaporated. The residue was purified by gel permeation
chromatography (Sephadex LH-20, 40 3.5 cm, MeOH/H2O, 1:1) to
afford the polyol (1) as a clear gum (4.5 mg, 90%), [ ]D –18.6° (H2O).
13C n.m.r. (125.8 MHz, D2O) 17.64, C 6B; 57.40, OMe; 60.04, 60.10,
C 6C,6D; 61.42, C 7A; 62.76, C 4B; 71.69, C 4A; 73.06, 73.18, 73.81,
74.01, 74.11, 74.25, 74.43, 74.91, 74.94, 76.33, 78.66, 78.86,
C (1,5,6)A,(2,3,5)B,(2,3,4,5)C,(2,3,4,5)D; 102.52, C 1C; 102.75, C 1B;
103.27, C 1D; 138.92, C 3A. The signal for C 2A could not be located.
35
+•
( Cl) (M) requires 1286.5581].
Methyl O-(6-Deoxy-2,3-di-O-pivaloyl- -D-galactopyranosyl)-(1 4)-
O-(2,3,6-tri-O-benzyl- -D-glucosyl)-(1 4)-2,3,6-tri-O-benzyl- -D-
glucoside (42)
The chloroacetate (41) (800 mg, 892 µmol) was treated as for (31)
above to afford, after flash chromatography (5–10% EtOAc/toluene),
the alcohol (42) as a foam (780 mg, 91%), [ ]D +18.1° (Found: C, 70.2;
1
H, 7.2. C71H86O17 requires C, 70.4; H, 7.2%). H n.m.r. (500 MHz)
1.13, 1.18, 2s, 18H, CMe3; 1.16, d, J5,6 6.5 Hz, 3H, H 6A; 3.10, m, H 5B;
3.27–3.42, 3.54–3.70, 2m, H 5A,(2,3,6,6)B,(2,3,5,6)C; 3.55, s, OMe;
3.68, br d, J3,4 3.3, J4,5 < 0 Hz, H 4A; 3.85, dd, J5,6 3.9, J6,6 10.8 Hz, H6C;
3.96, dd, J3,4 < J4,5 9.6 Hz, H 4C; 4.11, dd, J3,4 < J4,5 8.9 Hz, H4B;
4.17–5.13, m, CH2Ph; 4.28, d, J1,2 7.8 Hz, H1C; 4.40, d, J1,2 7.8 Hz,
H1B; 4.41, d, J1,2 8.0 Hz, H 1A; 4.65, dd, J2,3 10.3 Hz, H3A; 5.14, dd,
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