Chemoenzymatic synthesis of carbasugars from iodobenzene

Article abstract of DOI:10.1039/b502009c

The versatile enantiopure cis-dihydrodiol metabolite 1, formed by bacterial metabolism of iodobenzene, has been used for the synthesis of the pyranose carbasugars (pseudosugars) carba-β-D-altropyranose 2, carba-α-L- galactopyranose 3, carba-β-D-idopyranos

Full text of DOI:10.1039/b502009c

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A R T I C L E
Chemoenzymatic synthesis of carbasugars from iodobenzene
Derek R. Boyd,*a Narain D. Sharma,a Nuria M. Llamas,a John F. Malone,a Colin R. O’Dowda
and Christopher. C. R. Allenb
a Centre for the Theory and Application of Catalysis, School of Chemistry, The Queen’s
University of Belfast, Belfast, UK BT9 5AG
b QUESTOR Centre, The Queen’s University of Belfast, Belfast, UK BT9 5AG
Received 8th February 2005, Accepted 15th March 2005
First published as an Advance Article on the web 18th April 2005
The versatile enantiopure cis-dihydrodiol metabolite 1, formed by bacterial metabolism of iodobenzene, has been
used for the synthesis of the pyranose carbasugars (pseudosugars) carba-b-D-altropyranose 2, carba-a-L-galactopyra-
nose 3, carba-b-D-idopyranose 4 and carba-b-L-glucopyranose 5. Substitution of the iodine atom by a carbomethoxy
group, stereoselective catalytic hydrogenation of an a,b-unsaturated ester, and regioselective inversion of one or two
allylic chiral centres are the key steps used in the synthesis of carbasugars 2–5. The relative and absolute
configurations of compounds 2–5 were established by a combination of stereochemical correlation, X-ray
crystallography and 1H-NMR spectroscopy.
galactopyranose ent-3 is one of the few carba-monosaccharides
Introduction
to have been obtained entirely by bacterial enzyme-catalysed
A wide range of cis-dihydrodiol metabolites has been reported
as a result of toluene dioxygenase (TDO)-catalysed asymmetric
dihydroxylation of monocyclic arene substrates, using mutant
synthesis.23 The carba-oligosaccharide fermentation product,
acarbose, was also found to be an enzyme inhibitor.24 Carba-
a-DL-glucopyranose, obtained by chemical synthesis, was found
and recombinant strains of bacteria.1–8 The constitutive mutant
to be an inhibitor of a glucokinase enzyme.25 The chemical
strain, Pseudomonas putida UV, has proved to be particularly
successful and to date more than 50 enantiopure cis-dihydrodiol
syntheses of all 16 racemic carbasugars, and most of the
enantiopure members of the series, have been reviewed.26,26 Prior
metabolites of mono-substituted benzene substrates have been
to this study, few enantiopure carbasugars had been synthesized
isolated. The cis-dihydrodiol metabolite of fluorobenzene was
from benzene cis-dihydrodiol precursors.15,28
exceptional – the only member of the series with a lower enan-
tiomeric excess (ee) value (60–70%).9 Although, enantiopure
Results and discussion
cis-dihydrodiols have been widely utilized in synthesis,1–8 the
majority of reports have focused on cis-dihydrodiols of toluene,
chlorobenzene and bromobenzene as synthetic precursors. The
cis-dihydrodiol derivative 1, first reported in 1991 as a bacterial
metabolite of iodobenzene,10 is undoubtedly the most synthet-
ically versatile cis-dihydrodiol derivative of the halogenated
benzene substrates. However, owing to its commercial unavail-
ability and less stable nature,11 cis-dihydrodiol 1 has received
relatively little attention as a synthetic precursor.9,12–17 Having
recently been able to produce large quantities of iodo-substituted
benzene cis-dihydrodiols, during a single biotransformation,
using in-house large-scale fermenters (100–150 L), a programme
designed to exploit its particular advantages over other substi-
tuted cis-dihydrodiols has been undertaken.
The enantiopure metabolite of iodobenzene, cis-(1S,2S)-1,2-
dihydroxy-1,2-dihydro-3-iodocyclohexa-1,3-diene 1, obtained
using the mutant bacterial strain P. putida UV4, contains two
chiral centres whose absolute configurations are identical to
those found at the C-3 and C-4 positions in the pyranose carba-
sugars carba-b-D-altropyranose 2 and carba-a-L-galactopyra-
nose 3. Protection of cis-diol 1, as the (3aS,7aS)-acetonide
derivative 6 (98% yield), followed by cis-dihydroxylation using
a catalytic quantity of osmium tetroxide in the presence of N-
methylmorpholine N-oxide in a solution of acetone–water af-
forded the (3aS,4R,5R,7aS)-diol acetonide isomer 7 exclusively
(87% yield), as reported (Scheme 1).16 Using similar conditions
to those employed earlier for the palladium-catalysed carbony-
lation of vinyl iodides [Pd(OAc)2/NaOAc/MeOH] under one
atmosphere of carbon monooxide,13 the cis-diol acetonide 7
was converted to the (3aR,6R,7R,7aS)-a,b-unsaturated ester
8 (81% yield). The overall yield of the key intermediate 8,
obtained by the four-step sequence (iodobenzene → 1→ 6 →
7 → 8), was >60%.
One of the major advantages of cis-dihydrodiol 1 is the
ease of replacement of the iodine atom by other atoms or
groups by single-step substitution, using hydrogenolysis or Stille
coupling (e.g. replacement by vinyl, ethynyl, alkyl, allyl, cyano,
sulfanyl), without OH group protection, which has resulted
in the availability of a much wider range of cis-dihydrodiols.9
Furthermore, the relatively large steric requirements of the
iodine atom, can be utilized to direct regio- and stereo-selectivity
of TDO-catalysed cis-dihydroxylation of substituted iodoben-
zene substrates. This selectivity has facilitated the synthesis of
new regio- and stereo-isomers of the cis- and trans-dihydrodiol
isomers of iodobenzene.13,17–21
The synthetic advantages of iodobenzene cis-dihydrodiol 1,
allied to its improved availability, prompted this study to exploit
its potential in the synthesis of four carbasugars (pseudosugars)
2–5 (Scheme 1). Owing to the structural similarities of pyranose
carbasugars with normal sugars, but with resistance of carba-
sugars to ring-opening (mutatarotation) and enzyme-catalysed
hydrolysis, there has been an increasing interest in their synthesis
as potential enzyme inhibitors.22 The antibiotic carba-a-D-
Catalytic hydrogenation of a,b-unsaturated ester 8 (H2,
Rh/Al2O3, EtOH), under pressure (55 psi), was found to occur
preferentially from the less hindered face (trans to the acetonide
group) to give compound 14 as the major component of an
inseparable mixture of diastereoisomers (3aR,4S,6R,7R,7aS)
10 (35%) and (3aR,4R,6R,7R,7aS) 14 (65%) (Scheme 2). The
mixture was converted, directly, to the corresponding diben-
zoates 11/15 in order to effect a chromatographic separation
by multiple-elution Preparative Layer Chromatography (PLC)
(silica-gel, EtOAc–hexane). The less polar dibenzoate 11 (Rf 0.2)
was a crystalline compound (28% yield) whose structure and
stereochemistry were determined by NMR spectroscopic and
X-ray crystallographic analysis. Based on the known absolute
configuration of acetonide 6, an X-ray crystal structure analysis
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3
1 9 5 3
©

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Scheme 1 Reagents and conditions: i 2,2-DMP (98%); ii OsO4, Me2CO, H2O (87%); iii Pd(OAc)2, CO, NaOAc, MeOH (81%); iv BzCl, C6H5N (95%).
Scheme 2 Reagents and conditions: i Rh/Al2O3, H2; ii BzCl, C5H5N (28% from 8); iii LiAlH4 (74%); iv TFA (90%); v Ac2O, C5H5N (78%); vi
Rh/Al2O3, H2; vii BzCl, C5H5N (56% from 8); viii LiAlH4 (76%); ix TFA (81%); x Ac2O, C5H5N (84%).
showed that compound 11 had the (3aR,4S,6R,7S,7aR) absolute
configuration (Fig. 1). The carbasugar ring had a pseudo-chair
conformation with the carbomethoxy and benzoate groups cis
to each other and trans to the acetonide group.
Reduction (LiAlH4), of the three ester groups of compound
(3aR,4S,6R,7S,7aR)-11 yielded (3aS,4R,5R,7R,7aR)-acetonide
triol 12 (74% yield). Acid-catalysed deprotection (TFA) gave
(1R,2R,3R,4R,5R)-carba-b-D-altropyranose 2 ([a]D + 44.3, 90%
yield), which after purification by charcoal/Celite chromatog-
raphy, was further characterized as the penta-acetate 13 ([a]D
−7.8, 78% yield, Scheme 2). Following a different approach,
(1S,2S)-iodobenzene cis-dihydrodiol 1 had earlier been used
as a precursor in an eight-stage synthesis of the penta-acetate
derivative 13 of carba-b-D-altropyranose 2.15
The absolute configurations at the five chiral centres, of
dibenzoate 11 (Fig. 1), are identical to those found in the
derived carbasugar 2. Similarly, the X-ray crystal structure
Fig. 1 X-Ray structure of dibenzoate (3aR,4S,6R,7S,7aR)-11.
of compound 11 allowed the absolute configuration of the
epimeric dibenzoate 15 to be rigorously assigned. A similar
synthetic sequence was adopted, utilizing the more polar
(3aR,4R,6R,7S,7aR)-dibenzoate 15 (Rf 0.15) as precur-
sor to (3aS,4R,5R,7S,7aR)-acetonide triol 16 (76% yield),
1 9 5 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3

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Scheme 3 Reagents and conditions: i HCl, MeOH (90%); ii PPh3, DEAD, 4-NO2.C6H4CO2H (70%); iii NaOH, MeOH (87%); iv 2,2-DMP, p-TSA
(89%); v Ac2O, C5H5N (95%); vi CO, Pd(OAc)2, NaOAc, MeOH (87%); vii Rh/Al2O3, H2, EtOH (40%), viii LiAlH4, THF (81%); xi HCl, MeOH
(79%), x Ac2O, C5H5N (97%).
(1R,2R,3R,4R,5S)-carba-a-L-galactopyranose 3 ([a]D −59.2,
81% yield), and (1S,2R,3R,4R,5R)-penta-acetate 17 ([a]D −42.2,
84% yield; Scheme 2). Carbasugar 3 had earlier been synthesized
in enantiopure form, and characterized as a penta-acetate 17,
using a different precursor and synthetic route.28 Penta-acetates
13 and 17 were found to have comparable NMR and chiroptical
data to the literature values.15,28
1,2-dihydro-3-iodocyclohexa-1,3-diene 1. The first synthetic
approach to carbasugar 5 involved inversion of configuration
at two chiral allylic centres; a synthetic sequence involving con-
comitant inversion of configuration at these centres, in tetraol 28,
was developed (Scheme 4). Acid-catalysed deprotection, of cis-
diol acetonide 7 (HCl/MeOH), gave (1R,2R,3S,4S)-anti-tetraol
28 (85% yield). Treatment of tetraol 28 with 1-bromocarbonyl-
1-methylethyl acetate yielded the corresponding (1S,2R,5S,6S)-
dibromo diacetoxy derivative 29 (87% yield), with inversion
of configuration at both allylic chiral centres. The allylic
bromine atoms in compound 29 were both replaced with acetate
groups, with retention of configuration, using the Woodward–
Winstein reaction conditions (AgOAc/AcOH/Ac2O) to give
(1R,2S,5R,6S)-tetra-acetate 30 (77% yield). Substitution of the
iodine atom in compound 30 with a carbomethoxy group
gave unsaturated (3S,4R,5R,6S)-tetra-acetate 31 (73% yield).
Catalytic hydrogenation of compound 31 gave, exclusively, the
saturated (1R,2S,3R,4R,5S)-tetra-acetate 32 (80% yield) as a
crystalline compound. X-Ray crystal structure analysis of com-
pound 32 showed that it exists in the chair conformation with the
acetate and carbomethoxy groups all adopting equatorial posi-
tions and the overall structure having a (1R,2S,3R,4R,5S) ab-
solute configuration, based on the known (1S) configuration of
cis-dihydrodiol 1 (Fig. 2). The crystallographic asymmetric unit
consists of two independent molecules which differ only in some
torsion angles along the acetate and carbomethoxy side-chains.
The synthesis of (1R,2R,3R,4S,5R)-carba-b-D-idopyranose 4,
from (1S,2S)-cis-dihydrodiol metabolite 1 (Schemes 1 and 3),
required inversion of configuration at the C-2 chiral centre of
compound 1. This was achieved, indirectly, through the sequence
1→ 6 → 7 → 9 → 18 → 19 → 20 involving protection, dihydrox-
ylation, protection, deprotection, inversion, and deprotection
steps. Thus, treatment of the (3aS,4R,5R,7aS)-diol acetonide
7 with benzoyl chloride in pyridine gave (3aR,4S,5R,7aS)-
dibenzoate 9 (95% yield, Scheme 1), which was, in turn, partially
deprotected under acidic conditions to yield (1S,2R,5S,6R)-
diol dibenzoate 18 (90% yield) (Scheme 3). Application of
the Mitsunobu inversion procedure on diol 18 was found to
occur, exclusively, at the allylic position, to give (1R,4R,5S,6S)-
p-nitrobenzoate 19 (70% yield). Alkaline hydrolysis of triester
19 gave (1R,2R,3S,4R)-tetraol 20 (87% yield). The vicinal cis-
diol moiety in intermediate 20 was protected by formation of
(3aS,4R,5R,7aR)-acetonide 21 (89% yield), while the vicinal
trans-diol group was protected as (3aR,4S,5R,7aR)-diacetate 22
(95% yield).
Palladium-catalysed carbonylation conditions (cf. 7 → 8,
Scheme 1) were employed to replace the iodine atom in com-
pound 22 to give the required (3aR,6S,7S,7aR)-triester 23 (87%
yield, Scheme 3). Catalytic hydrogenation of the alkene bond in
compound 23, under the conditions used earlier (8 → 10 and 14,
Scheme 2), occurred from the less hindered face (trans to the ace-
tonide and proximate ester groups) to yield (3aR,5S,6S,7S,7aR)-
triester 24 (40% yield). Unfortunately, the hydrogenation of
alkene 23 was accompanied by a competing hydrogenolysis
reaction of the allylic acetyloxy group to give (3aR,5S,7R,7aR)-
diester 25 (60% yield), which could be readily separated from the
required triester 24 by chromatography. Reduction (LiAlH4) of
all three ester groups in compound 24 gave (3aR,4R,5S,6R,7aR)-
triol 26 (81% yield), which was deprotected under acidic
conditions to give the target molecule (1R,2R,3R,4S,5R)-carba-
b-D-idopyranose 4 ([a]D −6.1, 79% yield). This carbasugar was
also characterized as the (1R,2R,3R,4S,5R)-penta-acetate 27
([a]D −14.0, 97% yield) (Scheme 3).
Scheme 4 Reagents and conditions: i HCl/MeOH (85%); ii AcOCMe2-
COBr (87%); iii AgOAc/AcOH/Ac2O (77%); iv Pd(OAc)2, CO, NaOAc,
THF, H2O (73%); v Rh/Al2O3, H2 (80%); vi LiAlH4 (12%); vii Ac2O
(95%).
The last pyranose carbasugar, (1S,2R,3R,4S,5S)-carba-b-
L-glucopyranose 5, required the original (2S) absolute con-
figuration to be inverted in the precursor, cis-1,2-dihydroxy-
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3
1 9 5 5

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order to perform these steps in satisfactory yields with the
required stereochemistry, several approaches were investigated.
The optimal procedure involved protection of the free hy-
droxyl group of triester 38 as (1R,4S,5R,6S)-TBDMS ether
39 (93% yield) and deprotection via ester hydrolysis to give
(1S,2R,3S,4R)-triol 40 (86% yield). The iodine atom in the latter
compound was then replaced by a carbomethoxy group. The
resulting a,b-unsaturated (3S,4R,5R,6S)-ester 41 (69% yield)
was hydrogenated (H2, Rh/Al2O3, EtOH) to give, exclusively,
the saturated (1R,2S,3R,4R,5S)-ester 42 (80% yield). The 1R ab-
solute configuration at the new chiral centre at C-1 in compound
42, relative to the other chiral centres of known configuration,
was established using 1H-NMR spectroscopy. The coupling
constant, between H-1 and H-2 hydrogens in hydrogenated ester
42 was found to be 10.0 Hz, which was similar to the coupling
constant (11.0 Hz) found for the saturated methyl ester 32
whose stereochemistry was established by X-ray crystal structure
analysis. Hence, a trans relationship between the methyl ester at
C-1 and the adjacent hydroxyl at C-2 was established. Formation
of (1S,2S,3R,4R,5S)-tri-TBDMS ester 43 (95% yield) followed
by reduction (LiAlH4) of the ester group gave partially protected
alcohol derivative (1S,2R,3R,4S,5S)-tri-TBDMS ether 44 (82%
yield) of the required pyranose carbasugar. Deprotection of
compound 44 (HCl/MeOH) gave (1S,2R,3R,4S,5S)-carba-b-
L-glucopyranose 5 ([a]D −6.5, 78% yield) which was purified
using a charcoal/Celite column and further characterized as
(1S,2S,3R,4R,5S)-penta-acetate 33 ([a]D −5.4, 97% yield). The
chiroptical and spectroscopic data for compound 33 proved to
be similar to that reported.29
Fig. 2 X-Ray structure of (1R,2S,3R,4R,5S)-tetra-acetate 32.
Reduction (LiAlH4) of tetra-acetate 32 gave, after purifica-
tion, the required (1S,2R,3R,4S,5S)-carba-b-L-glucopyranose
5 in low yield ([a]D −6.1, 12%). Although the synthesis of
carbasugar 5 from cis-dihydrodiol 1 was achieved in eight steps
only, using the sequence shown in Scheme 4, a surprisingly low
yield was obtained in the final step compared with similar reduc-
tion steps in the earlier carbasugar syntheses (10 → 12, 14 →
16, 24 → 26, Schemes 2 and 3).
In an attempt to obtain carbasugar 5 in a higher yield, an
alternative synthetic strategy was developed. Two sequential
Mitsunobu inversions, exclusively at the allylic alcohol centres,
were the key steps of this synthesis (Scheme 5). Thus, employing
the Mitsunobu conditions (cf. Scheme 3), the first allylic chiral
centre in (3aS,4R,5R,7aS)-cis-diol acetonide 7 was inverted
to give (3aS,4S,5S,7aS) 4-nitrobenzoate 34 (80% yield). Base-
catalysed hydrolysis of ester 34 gave (3aS,4R,5S,7aS)-trans-
diol acetonide 35 (82% yield), which was protected as the
corresponding (3aS,4S,5R,7aS)-trans-dibenzoate acetonide 36
(93% yield). Removal of the acetonide protecting group from
compound 36 under acidic conditions (HCl/MeOH) gave
(1S,4S,5R,6S)-cis-diol dibenzoate 37 (86% yield). A further
stereoselective Mitsunobu inversion at the second allylic chiral
centre resulted in the formation of (1R,4S,5S,6S)-triester 38
(80% yield) which had the correct absolute configurations at
the four chiral centres required for the synthesis of carba-b-L-
glucopyranose 5 (Scheme 5).
Conclusion
Using the enantiopure (1S,2S)-cis-dihydrodiol metabolite of
iodobenzene 1 as precursor, it has been possible to obtain
the four pyranose carbasugars, carba-b-D-altrose 2, carba-a-
L-galactose 3, carba-b-D-idose 4 and carba-b-L-glucose 5. The
opposite (1R,2R)-cis-dihydrodiol enantiomer of iodobenzene 1,
now available to us via chemoenzymatic routes, will allow the
synthesis of the enantiomeric pseudosugars 2, 3, 4 and 5. The
synthetic methods thus described will allow 8 of the 32 possible
pyranose carbasugars to be synthesized from the enantiomeric
cis-dihydrodiol derivatives of iodobenzene. Chemoenzymatic
methods have also recently been developed in our laboratories
to produce all of the possible regioisomers and enantiomers of
both cis- and trans-dihydrodiol metabolites from cis-dihydrodiol
precursors, and this should allow the synthesis of an even wider
range of carbasugars.
The next phase of the synthesis involved the substitution
of an iodine atom of a vinyl iodide with a carbomethoxy
group, followed by a catalytic hydrogenation step, using similar
conditions to those already discussed (cf. Schemes 1–3). In
Scheme 5 Reagents and conditions: i PPh3, DEAD, 4-NO2.C6H4CO2H (80%); ii K2CO3, MeOH (82%); iii BzCl, C5H5N (93%); iv HCl, MeOH
(86%); v PPh3, DEAD, 4-NO2.C6H4CO2H (80%); vi TBDMSTf (93%); vii NaOH, MeOH (86%); viii CO, Pd(OAc)2, NaOAc, THF, H2O (69%); ix
Rh/Al2O3, H2 (80%); x TBDMSTf (95%); xi LiAlH4 (82%); xii TBAF, THF (78%); xiii Ac2O, C5H5N (97%).
1 9 5 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3

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monoxide until all of the starting material had reacted (ca. 6 h).
Removal of the solvent from the reaction mixture under reduced
pressure and purification of the EtOAc-soluble portion of the
crude product by PLC (60% EtOAc in hexane) yielded a,b-
unsaturated methy◦l ester 8 as a white, crystalline solid (0.32 g,
81%); mp 144–146 C, (lit.30 143–145 ◦C); (Rf 0.2, 60% EtOAc in
hexane); [a]D −39 (c 0.6, CHCl3), (lit.30 [a]D −41); dH (500 MHz,
CDCl3) 1.36, 1.41 [3H × 2, s, –C(Me)2], 2.78 (1H, d, J 3.7, –OH),
2.89 (1H, d, J 7.0, –OH), 3.82 (3H, s, –OMe), 4.25 (1H, dd, J 7.0,
J 3.5, 7-H), 4.48 (1H, m, 7a-H), 4.52 (1H, br s, 6-H), 5.04 (1H,
dd, J3a,7a 5.8, J3a,5 1.2, 3a-H), 6.87 (1H, dd, J5,6 2.6, J5,3a 1.3, 5-H).
Experimental
1H-NMR spectra were recorded at 300 MHz (Bruker Avance
DPX-300) and at 500 MHz (Bruker Avance DRX-500). Chemi-
cal shifts (d) are reported in ppm relative to SiMe4 and coupling
constants (J) are given in Hz. Mass spectra were recorded at
70 eV on a VG Autospec Mass Spectrometer, using a heated
inlet system. Accurate molecular weights were determined by
the peak matching method with perfluorokerosene as standard.
Elemental microanalyses were obtained on a Perkin-Elmer 2400
CHN microanalyser. Optical rotation ([a]D) measurements were
carried out with a Perkin-Elmer 214 polarimeter at ambient
◦
temperature (ca. 20 C) and are expressed in units of 10−1
Hydrogenation of compound 8
deg cm2 g−1. Flash column chromatography and PLC were
preformed on Merck Kieselgel type (250–400 mesh) and PF
A solution of a,b-unsaturated methyl ester 8 (0.4 g, 1.64 mmol)
in ethanol (20 cm3) was stirred under an atmosphere of H2 (55 psi
for 20 h) in the presence of 5% Rh/Al2O3 catalyst (0.05 g). The
catalyst was removed by filtration and the solvent distilled off to
give the crude hydrogenated product as an inseparable mixture of
diastereoisomers 10 and 14 (0.41 g). The mixture was converted
(benzoyl chloride/pyridine) into the corresponding dibenzoates
11 and 15 which could be separated by multiple-elution PLC
(15% EtOAc in hexane).
respectively. Merck Kieselgel 60F254 analytical plates were
254/366
used for TLC.
(3aS,7aS)-4-Iodo-2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxole 6
To a stirred solution (0 ◦C) of cis-(1S,2S)-1,2-dihydroxy-3-
iodocyclohexa-3,5-diene 1 (0.9 g, 3.8 mmol) in a mixture of
acetone (5 cm3) and 2,2-dimethoxypropane (5 cm3) was added
p-toluenesulfonic acid (0.075 g) and the reaction mixture was
allowed to warm to room temperature. When the starting
material had reacted completely (ca. 4 h, TLC analysis), the
solvents were removed under reduced pressure, the residual
material extracted with Et2O (50 cm3), and the ether extract
washed with water (2 × 15 cm3). The dried extract (Na2SO4) was
evaporated and the crude product obtained was purified by flash
column chromatography, to furnish the acetonide derivative 6 as
colourless, viscous oil (1.03 g, 98%); (Rf 0.26, 10% diethyl ether
in hexane); [a]D +122 (c 0.97, CHCl3); (Found: M+, 278.0010;
C9H11127IO2 requires 278.0009); dH (300 MHz, CDCl3) 1.43, 1.45
[3H × 2, s, –C(Me)2], 4.64 (1H, dd, J7a,3a 8.0, J7a,7 4.0, 7a-H), 4.73
(1H, d, J3a,7a 8.0, 3a-H), 5.78 (1H, dd, J6,7 10.0, J6,5 6.2, 6-H),
6.00 (1H, dd, J7,6 10.0, J7,7a 4.0, 7-H), 6.66 (1H, d, J5,6 6.2, 5-H);
m/z (EI) 278 (M+, 14%), 163 (34), 248 (12), 209 (54), 167 (22),
145 (24), 112 (87), 99 (23), 72 (10), 51 (17), 43 (100).
Methyl (3aR,4S,6R,7S,7aR)-6,7-di(benzoyloxy)-2,2-
dimethylperhydro-1,3-benzodioxole-4-carboxylate 11
White, crystalline solid (0.21 g, 28%); mp 156–158 ◦C (from
Et2O–hexane); (Rf 0.2, 20% EtOAc in hexane); [a]D −71 (c 0.42,
CHCl3); (Found C 66.0, H 5.6l C25H26O8 requires C 66.1, H
5.8%); dH (500 MHz, CDCl3) 1.42, 1.59 [3H × 2, s, –C(Me)2],
2.34 (1H, ddd, J 14.5, J 6.0, J 3.0, 5-H), 2.55 (1H, m, 5ꢀ-H),
3.11 (1H, m 4-H), 3.46 (3H, s, –OMe), 4.60 (1H, dd, J7a,7 6.4,
J7a,3a 5.0, 7a-H), 4.90 (1H, t, J3a,4 = J3a,7 5.0, 3a-H), 5.51 (1H,
dd, J7,7a 6.4, J7,6 3.3, 7-H), 5.61 (1H, m, 6-H), 7.37–7.44 (4H, m,
Ar–H), 7.54 (2H, m, Ar–H), 7.93 (2H, m, Ar–H), 7.99 (2H, m,
Ar–H); dC (75 MHz, CDCl3) 26.24, 26.47, 28.20, 41.05, 52.16,
69.78, 72.35, 73.99, 74.82, 109.44, 128.39, 128.46, 129.31, 129.40,
129.48, 129.60, 129.77, 129.82, 133.26, 133.32, 165.36, 165.70,
173.00 (×3).
Crystal data for 11. C25H26O8, M = 454.5, orthorhombic,
(3aS,4R,5R,7aS)-7-Iodo-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-
benzodioxole-4,5-diol 7
˚
a = 6.622(2), b = 8.534(2), c = 39.364(13) A, U = 2224.5(11)
3
˚
˚
A , T = 150(2) K, Mo-Karadiation, k = 0.71073 A, space group
P212121 (no. 19), Z = 4, F(000) = 960, Dx = 1.357 g cm−3, l =
0.101 mm−1, Siemens P4 diffractometer, x scans, scan range 1.0◦,
4.1 < 2h < 50.0◦, measured/independent reflections: 3144/2889,
direct methods solution, full matrix least squares refinement
on Fo2, anisotropic displacement parameters for most non-
hydrogen atoms (two carbon atoms could not be refined
anisotropically), hydrogens included at positions determined
by the geometry of the molecule using the riding model, with
isotropic vibration parameters, R1 = 0.096 for 1108 data with
Fo > 4r(Fo), 301 parameters, wR2 = 0.260 (all data), GoF =
A solution of acetonide 6 (0.8 g, 2.88 mmol) in a mixture of ace-
tone and water (5 : 1, 25 cm3) containing N-methylmorpholine
N-oxide (0.8 g) was treated with a catalytic amount of osmium
tetroxide. The reaction mixture was allowed to stir at ambient
temperature (12 h) and then a saturated solution of sodium
metabisulfite (1 cm3) was added; it was further stirred for
an hour. The solvents were removed in vacuo, a saturated
solution of sodium chloride (25 cm3) added to the residue and
the mixture extracted with EtOAc (3 × 25 cm3). The combined
organic extracts were dried (Na2SO4), the solvent evaporated,
and the crude product obtained was purified by flash column
chromatography (50% EtOAc in hexane) to furnish acetonide
diol 7 as a white, crystalline solid (0.78 g, 87%); mp 139–
141 ◦C; (Rf 0.35, 50% EtOAc in hexane); [a]D +28 (c 0.62,
CHCl3); (Found: M+, 311.9857; C9H13127IO4 requires 311.9860);
dH (500 MHz, CHCl3) 1.40, 1.44 [3H × 2, s, –C(Me)2], 4.25 (1H,
dd, J4,3a 6.5, J4,5 3.5, 4-H), 4.36 (1H, dd, J5,4 3.5, J5,6 3.2, 5-H),
4.42 (1H, dd, J3a,4 6.5, J3a,7a 5.4, 3a-H), 4.65 (1H, d, J7a,3a 5.4,
7a-H), 6.43 (1H, d, J6,5 3.2, 6-H); m/z (EI) 312 (M+, 3%), 254
(75), 212 (100), 109 (54), 85 (71), 81 (59), 57 (87), 39 (72), 29 (78).
−3
˚
1.06, Dqmin,max = −0.48/0.44 e A .
CCDC reference number 262885. See http://www.rsc.org/
suppdata/ob/b5/b502009c/ for crystallographic data in CIF
or other electronic format.
Methyl (3aR,4R,6R,7S,7aR)-6,7-di(benzoyloxy)-2,2-
dimethylperhydro-1,3-benzodioxole-4-carboxylate 15
White, crystalline solid (0.34 g, 56%); mp 154–155 ◦C (decomp.)
(from Et2O–hexane); (Rf 0.15, 20% EtOAc in hexane); [a]D −131
(c 0.3, CHCl3); (Found: C 66.0, H 5.7; C25H26O8 requires C 66.1,
H 5.8%); dH (500 MHz, CDCl3) 1.40, 1.59 [3H × 2, s, –C(Me)2],
Methyl (3aR,6R,7R,7aS)-6,7-dihydroxy-2,2-dimethyl-3a,6,7,7a-
tetrahydro-1,3-benzodioxole-4-carboxylate 8
2.31 (1H, dt, J5,5 9.8, J5,6 = J5,4 4.9, 5-H), 2.41 (1H, m, 5ꢀ-H),
ꢀ
3.26 (1H, m, 4-H), 3.78 (3H, s, OMe), 4.56 (1H, dd, J7a,7 7.6, J7a,3a
4.7, 7a-H), 4.82 (1H, t, J3a,4 = J3a,7a 4.7, 3a-H), 5.34 (1H, dd, J7,7a
7.6, J7,6 2.6, 7-H), 5.72 (1 H, m, 6-H), 7.36 (2H, m, Ar–H), 7.46
(2H, m, Ar–H), 7.51 (1H, m, Ar–H), 7.58 (1H, m, Ar–H), 7.96
(4H, m, Ar–H); dC (75 MHz, CDCl3) 25.44, 26.60, 28.33, 38.82,
Palladium(II) acetate (0.018 g, 5 mol%) was added to a solution
of acetonide diol 7 (0.5 g, 1.60 mmol) and NaOAc·3H2O (0.88 g,
6.4 mmol) in methanol (25 cm3). The reaction mixture was
stirred at room temperature under an atmosphere of carbon
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3
1 9 5 7

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52.68, 70.25, 73.97, 74.46, 76.29, 110.53, 128.52, 128.61, 128.70,
128.96, 129.15, 129.54, 129.97, 130.19, 133.53, 133.73, 165.64,
166.22, 171.81 (×3).
CHCl3), (lit.15 [a]D −8.1); dH (300 MHz, CDCl3) 1.83 (1H, q,
J6,6 = J6,5 = J6,1 11.4, 6-H), 1.98 (1H, m, 6ꢀ-H), 2.01, 2.02, 2.07,
ꢀ
2.11, 2.14 (3H each, s, 5 × –OCOCH3), 2.35 (1H, m, 1-H), 4.08
(2H, d, J 5.8, 7-H, 7ꢀ-H), 5.08 (1H, dd, J2,1 10.59, J2,3 3.0, 2-H),
5.20 (1H, m, 5-H), 5.27 (1H, m, 4-H), 5.34 (1H, dd, J3,4 4.89, J3,2
3.0, 3-H).
(3aS,4R,5R,7R,7aR)-7-Hydroxymethyl-2,2-dimethylperhydro-
1,3-benzodioxole-4,5-diol 12
A solution of dibenzoate 11 (0.28 g, 0.62 mmol) in anhydrous
THF (10 cm3) was treated with LiAlH4 powder (0.08 g,
2.1 mmol). After refluxing the reaction mixture (12 h) under
anhydrous conditions it was cooled in an ice bath and quenched
by the addition of a THF–water mixture. The precipitated inor-
ganic material was removed by filtration, the filtrate was dried
(Na2SO4) and concentrated in vacuo to yield the crude product
as an oil. Purification by flash column chromatography (10%
MeOH in CHCl3) afforded the partially protected carbasugar 12
as colourless oil (0.10 g, 74%); (Rf 0.35, 10% MeOH in CHCl3);
[a]D +46 (c 0.47, MeOH); (Found: M+ − Me, 203.0924; C9H15O5
requires 203.0919); dH (500 MHz, acetone-d6) 1.26, 1.38 [3H ×
2, s, –C(Me)2], 1.57 (1H, m, 6-H), 1.67–1.76 (2H, m, 7-H, 6ꢀ-H),
3.49 (1H, m, 1-H), 3.54 (2H, br s, 4-H, OH), 3.65 (3H, m, 1ꢀ-H,
2 × –OH), 3.97 (2H, m, 3a-H, 5-H), 4.16 (1H, dd, J7a,3a 5.3, J7a,7
3.7, 7a-H); dC (75 MHz, acetone-d6) 26.75, 29.10, 42.37, 64.88,
69.72, 71.80, 75.75, 79.65 (×2), 108.85; m/z (EI) 203 (M+ − Me,
78%), 143 (18), 125 (45), 95 (52), 79 (57), 71 (47), 59 (62), 57
(57), 43 (100), 29 (82).
(1R,2R,3R,4R,5S)-5-(Hydroxymethyl)cyclohexane-1,2,3,4-
tetraol (carba-a-L-galactopyranose) 3
Carbasugar 16 (0.13 g, 0.62 mmol) was deprotected (as com-
pound 12 → 2) to yield carba-a-L-galactopyranose 3 as a white
◦
solid (0.09 g, 81%); mp 162–163 C (MeOH), (lit.28 161.5–
162.5 ◦C); [a]D −59.2 (c 0.76, H2O), (lit.28 [a]D +66.3 for the
enantiomer); (Found: M+ − 2H2O, 142.0632; C7H10O3 requires
142.0630; dH (500 MHz, D2O) 1.60 (1H, m, 7ꢀ-H), 1.72 (1H, dt,
ꢀ
J7,5 = J7,1 3.7, J7,7 14.5, 7a-H), 2.06 (1H, m, 5-H), 3.56 (1H, dd,
J6,6 11, J6,5 6.4, 6-H), 3.70 (1H, dd, J6 ,6 11, J6 ,5 7.9, 6ꢀ-H), 3.76
(2H, t, J 1.1, 2-H, 3-H), 4.15 (2H, m, 1-H, 4-H); dC (75 MHz,
D2O) 27.90, 36.55, 62.88, 69.39, 70.36, 71.35, 71.53; m/z (EI)
142 (M+ − 2 × H2O, 15%), 124 (10), 116 (14), 111 (26), 86 (62),
83 (53), 73 (100), 57 (52).
ꢀ
ꢀ
ꢀ
[(1S,2R,3R,4R,5R)-2,3,4,5-Tetra(acetyloxy)cyclohexyl]methyl
acetate (carba-a-L-galactopyranose penta-acetate) 17
Carba-a-L-galactopyranose 3 (0.04 g, 0.25 mmol) was converted
(acetic anhydride–pyridine) to the penta-acetate 17 as a white
solid (0.08 g, 84%); mp 145–146 ◦C (Et2O–hexane); (lit.28 143–
144 ◦C); [a]D −42.2 (c 0.49, CHCl3), (lit.28 [a]D +43.2 for the
enantiomer); (Found M+ 388.1360; C17H24O10 requires 388.1369;
dH (500 MHz, CDCl3) 1.77 (2H, m, J 10.2, J 3.0, 6-H, 6ꢀ-H),
1.99, 2.01, 2.04 (3H each, s, 3 × –OCOCH3), 2.11 (6H, s, 2 ×
(3aS,4R,5R,7S,7aR)-7-Hydroxymethyl-2,2-dimethylperhydro-
1,3-benzodioxole-4,5-diol 16
Partially protected carbasugar 16 was similarly obtained from
dibenzoate 15 (0.3 g, 0.66 mmol) as compound 11 → 12.
Purification by PLC (10% MeOH in CHCl3) gave protected
pseudosugar 16 as a colourless oil (0.11 g, 76%); (Rf 0.37, 10%
MeOH in CHCl3); [a]D −47 (c 0.67, MeOH); (Found: M+ − Me,
203.0914; C9H15O5 requires 203.0919); dH (500 MHz, acetone-
ꢀ
ꢀ
–OCOCH3), 2.46 (1H, m, 1-H), 3.88 (1H, dd, J7,7 11, J7,1 5.7,
7-H), 3.96 (1H, dd, J7 ,7 11, J7 ,1 9.3, 7ꢀ-H), 5.18 (1H, dd, J4,3 10.9,
J4,5 2.9, 4-H), 5.23 (1H, dd, J3,4 10.9, J3,2 2.6, 3-H), 5.52 (1H, q,
ꢀ
ꢀ
ꢀ
d6) 1.22, 1.34 [3H × 2, s, –C(Me)2], 1.43 (1H, dt, J6,6 13.2, J6,5
=
J5,4 = J5,6 = J5,6 2.9, 5-H), 5.58 (1H, t, J2,3 = J2,1 2.6, 2-H); dC
J6,7 2.8, 6-H), 1.66 (1H, m, 6ꢀ-H), 2.34 (1H, m, 7-H), 3.48 (4H,
m, 4-H, 1-H, 2 × –OH), 3.62 (2H, m, 1ꢀ-H, –OH), 3.91 (1H,
m, 5-H), 3.96 (1H, dd, J3a,7a 4.9, J3a,4 6.9, 3a-H), 4.29 (1H, t,
J7a,3a = J7a,7 4.9, 7a-H); dC (75 MHz, acetone-d6) 26.94, 28.99,
35.48, 64.87, 70.19, 75.00, 75.87, 80.70 (×2), 109.06; m/z (EI)
203 (M+ − Me, 88%), 185 (10), 143 (12), 125 (56), 107 (38), 95
(54), 83 (63), 79 (74), 59 (78), 43 (100), 29 (79).
(75 MHz, CDCl3) 20.40, 20.42, 20.45, 20.67, 20.73, 26.33, 32.89,
62.61, 67.93, 67.95, 69.03, 69.30, 169.69, 169.72, 169.81, 169.98,
170.47; m/z (EI) 388 (M+, 12%), 329 (15), 268 (21), 243 (45), 226
(37), 166 (74), 124 (75), 43 (100).
(3aR,4S,5R,7aS)-5-(Benzoyloxy)-7-iodo-2,2-dimethyl-
3a,4,5,7a-tetrahydro-1,3-benzodioxol-5-yl benzoate 9
A solution of diol acetonide 7 (2.3 g, 7.4 mmol) in pyridine
(1 cm3) was treated with benzoyl chloride (2.5 g, 17.6 mmol);
the reaction mixture was left at room temperature overnight.
Pyridine was removed under reduced pressure and the residue
taken up in EtOAc (70 cm3). The EtOAc extract was washed
with 5% aq. NaHCO3 solution (2 × 40 cm3), dried (Na2SO4) and
concentrated (rotary evaporator) to give the crude dibenzoate 9
as a cream-coloured solid. Crystallization afforded dibenzoate 9
as a white, crystalline solid (3.5 g, 95%); mp 94–95 ◦C (MeOH);
(Rf 0.25, 15% Et2O in hexane); [a]D −70.0 (c 0.86, CHCl3);
(Found: C 52.9, H 4.0; C23H21127IO6 requires C 53.1, H 4.0%); dH
(500 MHz, CDCl3) 1.44, 1.53 [3H each, s, –C(Me)2], 4.62 (1H,
dd, J3a,7a 5.4, J3a,4 6.0, 3a-H), 4.82 (1H, d, J7a,3a 5.4, 7a-H), 5.80
(1H, dd, J4,3a 6.0, J4,5 3.7, 4-H), 5.87 (1H, d, J5,6 = J5,4 3.7, 5-H),
6.63 (1H, d, J6,5 3.7, 6-H), 7.35–7.58 (6H, m, Ar–H), 7.91–8.00
(4H, m, Ar–H); dC (125 MHz, CDCl3) 26.25, 27.65, 68.67, 69.47,
73.96, 78.84, 101.39, 110.69, 128.44, 128.53, 129.35, 129.39,
129.77, 129.87, 133.37, 133.47, 134.65, 134.79, 135.22, 135.49,
136.01, 165.36, 165.54; m/z (EI) 520 (M+, 6%), 504 (2), 398 (5),
341 (6), 336 (11), 213 (7), 105 (100), 147 (12), 78 (6), 43 (21).
(1R,2R,3R,4R,5R)-5-(Hydroxymethyl)cyclohexane-1,2,3,4-
tetraol (carba-b-D-altropyranose) 2
Protected carbasugar 12 (0.05 g, 0.25 mmol) was dissolved
in a mixture of TFA–THF–H2O (0.5 : 4 : 1; 2 cm3) and the
solution was kept at 50 ◦C (2 h). The reaction mixture was then
allowed to stir at room temperature overnight. The solvents were
removed under reduced pressure and the crude product purified
by charcoal–celite (1 : 1, v/v) column chromatography (water →
5% ethanol in water) to yield carba-b-D-altropyranose 2 as a
colourless syrup (0.04 g, 90%); [a]D +44.3 (c 0.44, MeOH), (lit.31
−49.5, for the enantiomer); (Found: M+ − 2H2O, 142.0624;
C7H10O3 requires 142.0629); dH (500 MHz, D2O) 1.59 (1H, q,
J7 ,7 = J7 ,5 = J7 ,1 12.1, 7ꢀ-H), 1.84 (1H, m, 7-H), 1.96 (1H, m,
5-H), 3.67 (2H, m, 3-H, 6-H), 3.79 (2H, m, 4-H, 6ꢀ-H), 4.04
(2H, m, 1-H, 2-H); dC (75 MHz, D2O) 28.79, 37.91, 63.58, 67.35,
68.65, 72.64, 73.05; m/z (EI) 142 (M+ − 2H2O, 18%), 124 (11),
116 (16), 111 (25), 86 (68), 83 (55), 73 (100).
ꢀ
ꢀ
ꢀ
[(1R,2R,3R,4R,5R)-2,3,4,5-Tetra(acetyloxy)cyclohexyl]methyl
acetate (carba-b-D-altropyranose penta-acetate) 13
(1S,2R,5S,6R)-2-(Benzoyloxy)-5,6-dihydroxy-4-iodo-3-
cyclohexenyl benzoate 18
To a solution of acetonide 9 (0.4 g, 0.8 mmol) in MeOH (20 cm3),
a HCl solution (1.5 M, 1 cm3) was added and the reaction
mixture kept at 50 ◦C until completion of the reaction (ca.
Carba-b-D-altropyranose 2 (0.03 g, 0.17 mmol) was converted to
penta-acetate 13 by reacting it with acetic anhydride in pyridine
at room temperature. The crude product was purified by column
chromatography (hexane → 50% Et2O in hexane) to yield penta-
acetate 13 as a colourless oil (0.05 g, 78%); [a]D −7.8 (c 1.43,
1 9 5 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3

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4 h, TLC analysis). Removal of the solvents from the reaction
mixture using a rotary evaporator and crystallization of the
residue gave white crystals of diol dibenzoate 18 (0.33 g, 90%);
chromatography (50% EtOAc in hexane) gave acetonide 21 as
a white, crystalline compound (1.0 g, 89%); mp 165–167 ◦C
(CHCl3–hexane); (Rf 0.34, 50% EtOAc in hexane); [a]D +15 (c
0.65, CHCl3); (Found: C 34.5, H 4.2; C9H13127IO4 requires C 34.6,
H 4.2%); dH (500 MHz, CDCl3) 1.38, 1.50 [3H × 2, s, –C(Me)2],
2.79 (1H, d, J 3.3, –OH), 2.93 (1H, d, J 6.7, –OH), 3.93 (1H, dd,
J4,3a 7.3, J4,5 6.9, 4-H), 4.03 (1H, d, J5,4 6.9, 5-H), 4.25 (1H, dd,
◦
mp 85–87 C (from MeOH); (Rf 0.23, 35% EtOAc in hexane);
[a]D −142 (c 0.58, CHCl3); (Found: M+ 480.0094; C20H17127IO6
requires 480.0070); dH (500 MHz, CDCl3), 4.50 (1H, dd, J6,1 8.9,
J6.5 3.7, 6-H), 4.57 (1H, d, J5,6 3.5, 5-H), 5.72 (1H, dd, J1,6 8.9,
J1,2 4.0, 1-H), 5.85 (1H, dd, J2,3 4.4, J2,1 4.0, 2-H), 6.65 (1H,
d, J3,2 4.4, 3-H), 7.36–7.46 (4H, m, Ar–H), 7.52–7.99 (6H, m,
Ar–H); dC (125 MHz, CDCl3) 68.26, 69.03, 69.52, 74.40, 105.32,
128.47, 128.50, 129.30, 129.79, 129.84, 130.12, 131.02, 131.34,
131.56, 131.88, 132.11, 133.45, 133.90, 165.52, 166.28; m/z (EI)
480 (M+, 23%), 401 (21), 367 (42), 335 (65), 236 (79), 205 (35),
169 (43), 149 (97), 136 (42), 122 (100), 105 (27), 31 (99).
J
3a,4 7.3, J3a,7a 6.2, 3a-H), 4.52 (1H, dd, J7a,7 3.9, J7a,3a 6.2, 7a-H),
6.56 (1H, dd, J7,7a 3.9, 7-H); dC (125 MHz, CDCl3) 20.08, 28.07,
72.61, 73.97, 74.46, 76.28, 106.97, 111.04, 134.52; m/z (EI) 312
(M+, 13%), 297 (42), 254 (26), 231 (14), 207 (65), 187 (12), 165
(45), 124 (18) 100 (76), 79 (67), 75 (60), 63 (41), 43 (100).
(3aR,4S,5R,7aR)-4-Acetyloxy-6-iodo-2,2-dimethyl-3a,4,5,7a-
tetrahydro-1,3-benzodioxol-5-yl acetate 22
(1R,4R,5S,6S)-4,5-Di(benzoyloxy)-6-hydroxy-2-iodo-2-
cyclohexenyl 4-nitrobenzoate 19
Acetonide diol 21 (0.1 g, 0.32 mmol) was acetylated (Ac2O–
pyridine) and the product purified by PLC (15% EtOAc in
hexane) to give diacetate 22 as a white, crystalline solid (0.12 g,
To a suspension of diol dibenzoate 18 (0.5 g, 1 mmol) in dry ben-
◦
3
˚
95%); mp 135–137 C (from MeOH); (Rf 0.41, 25% EtOAc in
zene (10 cm ) containing activated 3 A molecular sieves (0.5 g)
−1
=
hexane); [a]D −29 (c 0.58, CHCl3); mmax (cm ) 1753.6 (C O),
and triphenylphosphine (0.34 g, 1.3 mmol), DEAD (0.23 g,
1.32 mmol) was added drop-wise. After stirring the reaction
mixture at room temperature (0.5 h), p-nitrobenzoic acid (0.2 g,
1.2 mmol) was added and the stirring continued (0.5 h); it
was then refluxed at 90 ◦C (1.5 h). The molecular sieves were
filtered off, the solvent was removed from the filtrate, and the
crude product obtained was purified by column chromatography
(10% EtOAc in hexane) to yield p-nitrobenzoate 19 as an off-
1636.3 (C C); (Found: C 39.3, H 4.3; C13H17127IO6 requires C
=
39.4, H 4.3%); dH (500 MHz, CDCl3) 1.37, 1.51 [3H × 2, s, –
C(Me)2], 2.08, 2.14 (3H each, s, 2 × –OCOMe), 4.28 (1H, dd,
J
3a,4 8.6, J3a,7a 5.9, 3a-H), 4.50 (1H, dd, J7a,3a 5.9, J7a,7 4.5, 7a-H),
5.28 (1H, dd, J4,3a 8.6, J4,5 8.2, 4-H), 5.52 (1H, dd, J5,4 8.2, J5,7
2.0, 5-H), 6.69 (1H, dd, J7,7a 4.5, J7,5 2.0, 7-H); dC (125 MHz,
CDCl3) 20.86, 20.98, 26.34, 27.76, 71.29, 72.42, 73.77, 74.47,
101.74, 111.58, 135.93, 169.73, 170.04; m/z (EI) 381 (M+ − Me,
15%), 279 (43), 269 (80), 237 (100), 236 (25), 227 (14), 207 (5),
169 (77), 152 (21), 127 (29), 110 (63), 109 (39), 81 (16), 69 (5).
◦
white crystalline solid (0.44 g, 70%); mp 72 C; (Rf 0.23, 35%
EtOAc in hexane); [a]D −37 (c 0.75, CHCl3); (Found: C 51.25,
H 3.01; C27H20N127IO9 requires C 51.51, H 3.18%); dH (500 MHz,
CDCl3) 4.66 (1H, dd, J6,5 9.0, J6,1 6.3, 6-H), 5.64 (1H, dd, J5,6
9.0, J5,4 4.4, 5-H), 5.88 (1H, dd, J4,3 4.8, J4,5 4.4, 4-H), 5.91 (1H,
d, J1,6 6.3, 1-H), 6.87 (1H, d, J3,4 4.8, 3-H), 7.32–7.46 (10H,
m, Ar–H), 7.91–8.05 (4H, m, Ar–H); dC (125 MHz, CDCl3)
70.45, 71.12, 71.84, 79.98, 102.88, 125.32, 130.23, 130.34, 130.87,
131.01, 131.59, 132.59, 132.95, 133.04, 133.24, 134.56, 134.78,
134.99, 135.10, 135.33, 135.36, 136.36, 138.98, 152.50, 165.82,
167.28, 167.67; m/z (EI) 611 (M+ − H2O, 7%), 536 (67), 513
(21), 466 (12), 391 (64), 376 (77), 293 (6), 235 (6), 207 (15), 181
(77), 164 (36), 150 (100), 135 (18), 120 (32), 104 (67), 92 (36), 76
(62), 59 (48), 44 (34).
Methyl (3aR,6S,7S,7aR)-6,7-di(acetyloxy)-2,2-dimethyl-
3a,6,7,7a-tetrahydro-1,3-benzodioxole-5-carboxylate 23
a,b-Unsaturated methyl ester 23 was obtained from iododi-
acetate 22 (0.1 g, 0.25 mmol) using the palladium-catalyzed
carbonylation reaction conditions employed for the synthesis
of methyl ester 8. Purification of the crude product by PLC
(25% EtOAc in hexane) gave methyl ester 23 as a white solid.
Crystallization of the crude product, from EtOH, yielded methyl
ester 23 as colourless crystals (0.1 g, 87%); mp 102–105 ◦C (from
EtOH); (Rf 0.36, 30% EtOAc–hexane); [a]D +18 (c 0.65, CHCl3);
(Found: M+ − Me, 313.0923; C14H17O8 requires 313.0923); dH
(500 MHz, CDCl3) 1.38, 1.46 [3H × 2, s, –C(Me)2], 2.04, 2.07
(3H each, s, 2 × –OCOMe), 3.78 (3H, s, –CO2Me), 4.30 (1H, dd,
(1R,2R,3S,4R)-5-Iodo-5-cyclohexene-1,2,3,4-tetraol 20
To a solution of nitrobenzoate 19 (3.0 g, 4.8 mmol) in MeOH
(50 cm3), a 5% aq. NaOH solution (15 cm3) was added. The
reaction mixture was left at room temperature (2 h). The solvent
was then removed under reduced pressure, and water (25 cm3)
added to the concentrate. The aqueous solution was acidified
(2 M HCl), cooled, and the precipitated p-nitrobenzoic acid
filtered off. The filtrate was concentrated under reduced pressure
and the crude, syrupy material obtained was purified by column
chromatography (EtOAc → 10% MeOH in EtOAc) to give
tetraol 20 as colourless crystals (1.1 g, 87%); mp 145–147 ◦C
(from acetone–MeOH); (Rf 0.23, 10% MeOH in CHCl3); [a]D
−45 (c 0.46, MeOH); (Found: C 26.5, H 3.3; C6H9127IO4 requires
C 26.4, H 3.3%); dH (500 MHz, CD3OD) 3.54 (1H, dd, J2,3 10.6,
J2,1 4.1, 2-H), 3.63 (1H, dd, J4,3 7.5, J4,6 1.6, 4-H), 3.83 (1H, dd,
J3,2 10.6, J3,4 7.5, 3-H), 4.00 (1H, dd, J1,6 5.7, J1,2 4.1, 1-H), 6.53
(1H, dd, J6,1 5.7, J6,4 1.6, 6-H); dC (125 MHz, CD3OD) 68.55,
70.67, 72.10, 76.95, 108.82, 138.01; m/z (EI) 272 (M+, 2%), 217
(15), 199 (9), 188 (6), 170 (7), 152 (8), 149 (6), 129 (7), 113 (5),
91 (4), 81 (6), 70 (100), 55 (37), 32 (18).
J
7a,7 5.7, J7a,3a 5.5, 7a-H), 4.72 (1H, dd, J3a,7a 5.5, J3a,4 4.0, 3a-H),
5.36 (1H, dd, J7,7a 5.7, J7,6 5.2, 7-H), 5.73 (1H, d, J6,7 5.2, 6-H),
7.00 (1H, d, J4,3a 4.0, 4-H); dC (125 MHz, CDCl3) 20.78, 20.84,
26.22, 27.65, 52.26, 65.74, 69.87, 70.80, 72.81, 111.36, 129.76,
137.05, 164.89, 169.43, 169.88; m/z (EI) 313 (M+ − Me, 90%),
298 (6), 225 (9), 212 (7), 211 (67), 179 (18), 169 (100), 168 (37),
141 (7), 139 (9), 137 (32), 136 (15), 109 (11), 69 (7), 59 (10).
Hydrogenation of methyl (3aR,6S,7S,7aR)-6,7-di(acetyloxy)-
2,2-dimethyl-3a,6,7,7a-tetrahydro-1,3-benzodioxole-5-
carboxylate 23
a,b-Unsaturated ester 23 (0.5 g, 1.5 mmol) was hydrogenated
(H2, 5% Rh/Al2O3, 35 psi, 10 h) in EtOH solution (15 cm3).
Purification and separation of the crude hydrogenated di-
astereoisomeric mixture by flash column chromatography (20%
EtOAc in hexane → 30% EtOAc in hexane) gave pure samples
of methyl esters 24 and 25.
Methyl (3aR,5S,6S,7S,7aR)-6,7-di(acetyloxy)-2,2-
dimethylperhydro-1,3-benzodioxole-5-carboxylate 24
(3aS,4R,5R,7aR)-6-Iodo-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-
benzodioxole-4,5-diol 21
The more polar methyl ester 24 formed white crystals (0.2 g,
40%); mp 120–121 ◦C (from EtOH); [a]D −9 (c 0.70, CHCl3);
(Found: M+ − Me, 315.0080; C14H19O8 requires 315.0080); dH
(500 MHz, CDCl3) 1.32, 1.52 [3H each, s, –C(Me)2], 2.11, 2.14
Iodotetraol 20 (1 g, 3.7 mmol) was converted into acetonide
diol 21 using the procedure described for the synthesis of
acetonide 6. Purification of the crude product by flash column
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3
1 9 5 9

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ꢀ
ꢀ
(3H × 2, s, 2 × –OCOMe), 2.13 (1H, ddd, J4,5 13.5, J4,3a 5.0, J4,4
1.74 (1H, ddd, J6,6 13.5, J6,1 4.0, J6,5 3.8, 6-H), 2.038, 2.040, 2.047,
2.049, 2.063 (3H each, s, 5 × –OCOMe), 2.05–2.06 (1H, m, 6ꢀ-H),
2.51–2.53 (1H, m, 1-H), 4.10–4.11 (1H, m, 7-H), 4.17 (1H, dd,
4.5, 4-H), 2.33–2.34 (1H, m, 4ꢀ-H), 2.90 (1 H, ddd, J5,4 13.5, J5,6
ꢀ
4.8, J5,4 4.5, 5-H), 3.70 (3H, s, –CO2Me), 4.04 (1H, dd, J7a,7
=
J7 ,1 11.1, J7 ,7 7.7, 7ꢀ-H), 4.97–4.98 (1H, m, 5-H), 5.11 (1H, dd,
J4,3 5.4, J4,5 3.5, 4-H), 5.22 (1H, dd, J2,3 5.0, J2,1 4.8, 2-H), 5.28
(1H, dd, J3,4 5.4, J3,2 5.0, 3-H); dC (125 MHz, CDCl3) 20.70,
20.77, 20.80, 20.98, 21.12, 24.82, 34.85, 63.59, 68.14, 68.25,
68.43, 68.65, 168.91, 169.52, 169.62, 169.97, 170.73; m/z (EI)
388 (M+, 14%), 329 (27), 287 (45), 268 (12), 243 (22), 209 (9),
167 (15), 132 (33), 101 (40), 61 (11), 43 (100).
ꢀ
ꢀ
J7a,3a 5.2, 7a-H), 4.27 (1H, dd, J3a,7a 5.2, J3a,4 5.0, 3a-H), 5.08
(1H, ddd, J7,6 6.7, J7,7a 5.2, J7,5 1.5, 7-H), 5.68 (1H, dd, J6,7 6.7,
J6,5 4.8, 6-H); dC (125 MHz, CDCl3) 22.27, 22.37, 27.55, 27.60,
27.69, 41.08, 53.48, 70.74, 71.75, 74.11, 77.53, 111.15, 170.70,
171.03, 171.56; m/z (EI) 315 (M+ − Me, 100%), 273 (6), 241
(10), 213 (19), 170 (13), 171 (29), 153 (59), 139 (8), 128 (6), 11
(10), 109 (14), 95 (11), 83 (8), 69 (6), 59 (15).
Methyl (3aR,5S,7R,7aR)-7-acetyloxy-2,2-dimethylperhydro-
1,3-benzodioxole-5-carboxylate 25
(1R,2R,3S,4S)-5-Iodo-5-cyclohexene-1,2,3,4-tetraol 28
Iodotetraol 28 was obtained by acid-catalysed hydrolysis of
acetonide diol 7 (0.5 g, 1.6 mmol) using the method described
for the synthesis of benzoate diol 18, as a white, crystalline solid
(0.37 g, 85%); mp 160–162 ◦C (from MeOH–CHCl3); (Rf 0.26,
10% MeOH in CHCl3); [a]D −82 (c 0.5, MeOH); (Found: M+
272.0913; C6H9127IO4 requires 272.0910); dH (500 MHz, D2O)
3.96–3.97 (1H, m, 3-H), 4.10–4.11 (1H, m, 2-H), 4.26–4.27 (1H,
m, 1-H), 4.48–4.49 (1H, m, 4-H), 6.54–6.55 (1H, m, 6-H); dC
(125 MHz, D2O) 67.83, 67.90, 68.73, 74.62, 103.00, 140.12; m/z
(EI) 272 (M+, 2%), 254 (17), 236 (22), 187 (5), 146 (2), 128 (4),
117 (8), 113 (17), 85 (31), 71 (74), 57 (79), 43 (100), 39 (17), 32
(13), 29 (27).
The less polar methyl ester 25 was also obtained as a white,
crystalline compound (0.25 g, 60%); mp 53–55 ◦C (from EtOH);
[a]D +8 (c 0.61, CHCl3); (Found: M+ 271.9988; C13H20O6 requires
271.9985); dH (500 MHz, CDCl3) 1.33, 1.48 [3H × 2, s, –C(Me)2],
1.84–1.85 (1H, m, 6-H), 1.96–1.97 (1H, m, 4ꢀ-H), 2.07 (3 H, s,
–OCOMe), 2.11–2.12 (2H, m, 4-H, 6ꢀ-H), 2.61–2.63 (1H, m, 5-
H), 3.71 (3H, s, –CO2Me), 3.99 (1H, dd, J7a,3a 5.0, J7a,7 4.2, 7a-H),
ꢀ
4.28 (1H, ddd, J3a,4 11.0, J3a,4 5.4, J3a,7a 5.0, 3a-H), 5.33 (1H, dd,
7,6 9.3, J7,7a 4.2, 7-H); dC (125 MHz, CDCl3) 21.16, 26.08, 27.66,
J
28.46, 29.03, 34.77, 51.96, 69.76, 72.79, 74.58, 110.30, 169.37,
170.20; m/z (EI) 272 (M+, 24%), 213 (10), 143 (12), 132 (51), 109
(52), 81 (94), 53 (94), 51 (100), 29 (90).
(1S,2R,5S,6S)-6-(Acetyloxy)-2,5-dibromo-3-iodo-3-
cyclohexenyl acetate 29
(3aS,4R,5S,6R,7aR)-6-Hydroxymethyl-2,2-dimethylperhydro-
1,3 -benzodioxole-4,5-diol 26
To a solution of the iodotetraol 28 (0.8 g, 3 mmol) in dry
acetonitrile (10 cm3) at 0 ◦C under a nitrogen atmosphere
was added drop-wise 1-bromocarbonyl-1-methylethyl acetate
(1.37 g, 6.6 mmol). The reaction mixture was stirred at 0 ◦C
(0.25 h) and then at room temperature (2 h). Most of the
solvent was then removed under reduced pressure, the residue
extracted with Et2O (2 × 50 cm3), the extract washed with 3%
aq. NaHCO3 (3 × 10 cm3), dried (Na2SO4) and concentrated
to give the crude bis-bromoacetate 29 as a light brown-coloured
foam. Crystallization of the crude product afforded colourless
crystals of bis-bromoacetate 29 (1.26 g, 87%); mp 70 ◦C (CHCl3–
hexane); [a]D +75 (c 0.50, CHCl3); (Found: M+ 484.0101;
C10H11127I81Br2O4 requires 484.0108); dH (500 MHz, CDCl3) 2.11,
2.13 (3H each, s, 2 × –OCOMe), 4.60 (1H, J5,6 5.3, J5,4 3.4, 5-H),
4.73 (1H, d, J2,1 5.5, 2-H), 5.41 (1H, dd, J1,6 7.4, J1,2 5.5, 1-H),
5.53 (1H, dd, J6,1 7.4, J6,5 5.3, 6-H), 6.70 (1H, d, J4,5 3.4, 4-H);
dC (125 MHz, CDCl3) 20.70, 20.75, 44.00, 52.80, 70.34, 79.89,
98.90, 140.01, 169.20, 169.67, m/z (EI) 484 (M+, 25%), 482 (47),
480 (26), 425 (32), 423 (12), 366 (19), 300 (10), 230 (21), 199 (57),
176 (38), 132 (5), 87 (54), 52 (40), 43 (100), 22 (10).
Reduction (LiAlH4–THF, 0.08 g, 2 mmol) of methyl ester
24 (0.23 g, 0.68 mmol) and subsequent purification of the
crude product by flash column chromatography (10% MeOH
in CHCl3) furnished protected carbasugar 26 as a colourless
oil (0.12 g, 81%); [a]D −7 (c 0.74, MeOH); (Found: M+ − Me,
203.0910; C9H15O5 requires 203.0919); dH (500 MHz, D2O) 1.22,
1.28 [3H × 2, s, –C(Me)2], 1.54–1.56 (2H, m, 7-H, 7ꢀ-H), 1.78–
1.79 (1H, m, 6-H), 3.43–3.44 (1H, m, 1ꢀ-H), 3.55 (1H, dd, J1,6 7.0,
ꢀ
J1,1 5.4, 1-H), 3.68 (1H, dd, J5,4 7.1, J5,6 4.0, 5-H), 3.74 (1H, dd,
J4,3a 11.0, J4,5 7.1, 4-H), 3.83 (1H, dd, J7a,3a 5.6, J7a,7 5.4, 7a-H),
4.11 (1H, J3a,4 11.0, J3a,7a 5.6, 3a-H); dC (125 MHz, CDCl3) 21.00,
23.89, 24.00, 33.26, 62.11, 66.80, 72.02, 75.35, 77.23, 109.11; m/z
(EI) 203 (M+ − Me, 35%), 185 (24), 149 (6), 143 (11), 125 (23),
111 (15), 107 (17), 95 (39), 91 (6), 84 (31), 79 (60), 73 (40), 67
(52), 59 (88), 55 (100).
(1R,2R,3R,4S,5R)-5-Hydroxymethyl-cyclohexane-1,2,3,4-
tetraol (carba-b-D-idopyranose) 4
Deprotection of acetonide group of carbasugar derivative 26
(0.08 g, 0.36 mmol) using the method described for the synthesis
of compound 18, followed by purification of the crude product
by charcoal–Celite (1 : 1, v/v) column chromatography (water →
10% EtOH in water), afforded carba-b-D-idopyranose 4 as
a colourless, viscous oil (0.05 g, 79%); [a]D −6.1 (c 0.91,
MeOH); (Found: M+ 178.0846; C7H14O5 requires 178.0841); dH
(500 MHz, D2O) 1.59–1.60 (1H, m, 6-H), 1.66–1.67 (1H, m,
(1R,2S,5R,6S)-2,5,6-Tri(acetyloxy)-4-iodo-3-cyclohexenyl
acetate 30
Silver acetate (0.4 g, 2.4 mmol) was added to a solution of bis-
bromoacetate 29 (0.3 g, 0.6 mmol) in a mixture of dry AcOH
(6 cm3) and Ac2O (0.6 cm3). The reaction mixture was gently
refluxed (1 h), cooled to room temperature and filtered through
a pad of Celite. The filtrate was concentrated under reduced
pressure and the crude product obtained was purified by PLC
(25% EtOAc in hexane) to yield tetra-acetate 30 as a white,
crystalline solid (0.09 g, 77%); mp 112–115 ◦C (from MeOH); (Rf
0.4, 25% EtOAc in hexane); [a]D +49 (c 0.78, CHCl3); (Found: C
38.2, H 4.0; C14H17127IO8 requires C 38.2, H 3.9%); dH (500 MHz,
CDCl3) 2.01, 2.03, 2.07, 2.12 (3H each, s, 4 × –OCOMe), 5.33
(1H, dd, J6,1 10.4, J6,5 7.4, 6-H), 5.38 (1H, dd, J1,6 10.4, J1,2 7.8, 1-
H), 5.46 (1H, dd, J2,1 7.8, J2,3 2.4, 2-H), 5.71 (1H, dd, J5,6 7.4, J5,3
2.4, 5-H), 6.39 (1H, d, J3,2 2.4, 3-H); dC (125 MHz, CDCl3) 20.51,
20.55, 20.74, 20.86, 70.45, 70.52, 72.09, 74.36, 97.81, 137.68,
169.53, 169.65, 169.80, 170.02; m/z (EI) 381 (M+ − OAc, 4%),
338 (8), 313 (6), 271 (10), 237 (11), 212 (3), 168 (5), 151 (4), 127
(23), 110 (11), 81 (5), 43 (100).
6ꢀ-H), 2.03–2.04 (1H, m, 5-H), 3.60 (1H, dd, J7,5 11.0, J7,7 6.4,
ꢀ
7-H), 3.66 (2H, m, 3-H, 7ꢀ-H), 3.74 (1H, dd, J4,5 = J4,3 4.3, 4-H),
3.90–3.91 (2H, m, 1-H, 2-H); dC (125 MHz, D2O) 27.10, 38.70,
62.76, 68.31, 71.66, 72.90, 73.37, m/z (EI) 178 (M+, 16%), 177
(100), 175 (72), 173 (32), 163 (17), 156 (14), 139 (27), 135 (32),
121 (47), 120 (14), 110 (9), 77 (8).
[(1R,2R,3R,4S,5R)-2,3,4,5-Tetra(acetyloxy)cyclohexyl]methyl
acetate 27
Carba-b-D-idopyranose 4 (0.05 g, 0.03 mmol) was converted
to penta-acetate 27 (Ac2O–pyridine), a white, crystalline solid
(0.11 g, 97%); mp 110–112 ◦C (from Et2O–hexane); [a]D −14.0
−1
=
(c 0.50, CHCl3); mmax (cm ) 1747.8 (C O); (Found: C 52.3, H
5.9; C17H24O10 requires C 52.6, H 6.2%); dH (500 MHz, CDCl3)
1 9 6 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3

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Methyl (3S,4R,5R,6S)-3,4,5,6-tetra(acetyloxy)-1-cyclohexene-
1-carboxylate 31
[(1S,2S,3R,4R,5S)-2,3,4,5-Tetra-acetyloxycyclohexyl]methyl
acetate 33
The palladium-catalyzed carbonylation reaction of iodotetra-
acetate 30 (0.4 g, 0.9 mmol), as described for compound 8,
gave a,b-unsaturated methyl ester 31 as a white, crystalline
solid (0.2 g, 73%); mp 122–124 ◦C (from MeOH); (Rf 0.45,
50% EtOAc in hexane); [a]D +23 (c 0.68, CHCl3); (Found: M+
372.0047; C16H20O10 requires 372.0056); dH (500 MHz, CDCl3)
2.04, 2.05, 2.07, 2.15 (3H each, s, 4 × –OCOMe), 3.76 (3H, s,
–CO2Me), 5.32–5.33 (2H, m, 4-H, 5-H), 5.68 (1H, dd, J3,4 4.1,
J3,2 3.8, 3-H), 6.01 (1H, d, J6,5 4.1, 6-H), 6.79 (1H, d, J2,3 3.8,
2-H); dC (125 MHz, CDCl3) 20.58, 20.64, 20.70, 20.74, 52.37,
69.02, 70.00, 70.33, 71.82, 130.18, 137.87, 156.61, 156.66, 156.73,
169.59, 169.86; m/z (EI) 372 (M+, 2%), 341 (5), 313 (9), 210 (82),
169 (99), 139 (37), 125 (17), 109 (13), 81 (7), 43 (100).
Carba-b-L-glucopyranose 5 (0.025 g, 0.14 mmol) was acetylated
(Ac2O–pyridine) to give carba-b-L-glucopyranose penta-acetate
33 as a colourless syrup (0.05 g, 95%); (Found: M+ 388.1371;
C17H24O10 requires 388.1369); [a]D −5.4 (c 0.71, CHCl3), (lit.29
[a]D −7.4, CHCl3); dH (500 MHz, MeOH) 1.54–1.55 (1H, m,
6-H), 2.04–2.05 (1H, m, 1-H), 1.99, 2.01, 2.03, 2.05, 2.06 (3H
each, s, 5 × –OCOMe), 2.16–2.18 (1H, m, 6ꢀ-H), 3.94 (1H, dd,
J7,7 11.4, J7,1 3.2, 7-H), 4.08 (1H, dd, J7 ,7 11.4, J7 ,1 5.1, 7ꢀ-H), 4.92
ꢀ
ꢀ
ꢀ
ꢀ
(1H, ddd, J5,6 12.5, J5,4 9.5, J5,6 4.9, 5-H), 5.03 (1H, dd, J3,4 = J3,2
9.5, 3-H), 5.10 (1H, dd, J4,3 = J4,5 9.5, 4-H), 5.16 (1H, dd, J2,1
=
J2,3 9.7, 2-H); dC (125 MHz, CDCl3) 20.53, 20.59, 20.72, 20.86,
21.13, 29.41, 36.35, 62.80, 70.59, 71.76, 72.74, 73.28, 169.80,
169.83, 169.90, 170.09, 170.69; m/z (EI) 388 (M+, 9%), 329 (6),
307 (2), 286 (4), 243 (6), 227 (11), 226 (40), 208 (20), 183 (21),
166 (92), 142 (10), 141 (19), 128 (22), 125 (25), 124 (100), 115
(16), 103 (13), 96 (32), 84 (60), 71 (17), 61 (5).
Methyl (1R,2S,3R,4R,5S)-2,3,4,5-tetra(acetyloxy)cyclohexane-
1-carboxylate 32
(3aS,4S,5S,7aS)-4-Hydroxy-7-iodo-2,2-dimethyl-3a,4,5,7a-
tetrahydro-1,3-benzodioxol-5-yl 4-nitrobenzoate 34
Catalytic hydrogenation of a,b-unsaturated methyl ester 31
(0.7 g, 1.8 mmol), as described for the synthesis of compound 24,
gave saturated methyl ester 32 as a white, crystalline solid (0.53 g,
Using Mitsunobu reaction conditions as described for the syn-
thesis of p-nitrobenzoate 19, acetonide diol 7 (0.2 g, 0.64 mmol)
was converted to p-nitrobenzoate 34 as a white, crystalline solid
(0.24 g, 80%); mp 77–80 ◦C (from EtOAc–hexane); (Rf 0.24,
30% EtOAc in hexane); [a]D −3 (c 0.68, CHCl3); (Found: M+ −
Me, 445.9739; C15H13127INO7 requires 445.9737); dH (500 MHz,
◦
80%); mp 139–141 C (from EtOH); [a]D +23 (c 0.68, CHCl3);
−1
=
mmax (cm ) 1736.3 (C O); (Found: C 51.2, H 5.7; C16H22O10
requires C 51.3, H 5.9%); dH (500 MHz, CDCl3) 1.76 (1H, ddd,
ꢀ
6,5 12.0, J6,6 4.6, J6,1 3.8, 6-H), 1.99, 2.01, 2.02, 2.03 (3H each, s,
J
4 × –OCOMe), 2.35 (1H, ddd, J6 ,1 14.0, J6 ,5 4.7, J6 ,6 4.6, 6ꢀ-H),
ꢀ
ꢀ
ꢀ
CDCl3) 1.45, 1.58 [3H × 2, s, –C(Me)2], 4.03 (1H, dd, J4,5
=
ꢀ
2.73 (1H, ddd, J1,6 14.0, J1,2 11.0, J1,6 3.8, 1-H), 3.67 (3H, s,
J4,3a 8.0, 4-H), 4.27 (1H, dd, J3a,4 8.0, J3a,7a 6.4, 3a-H), 4.75 (1H,
d, J7a,3a 6.4, 7a-H), 5.47 (1H, dd, J5,4 8.0, J5,6 2.3, 5-H), 6.49
(1H, d, J6,5 2.3, 6-H), 8.21, 8.28 (4H, m, Ar–H); dC (125 MHz,
CDCl3), 26.38, 28.48, 70.99, 74.88, 77.19, 79.42, 79.70, 97.03,
111.18, 124.00, 131.37, 135.18, 138.42, 151.18, 164.64; m/z (EI)
446 (M+ − Me, 17%), 294 (9), 236 (13), 228 (7), 166 (52), 150
(98), 120 (8), 117 (12), 110 (25), 106 (100), 91 (76), 81 (10), 76
(15), 65 (20).
ꢀ
–CO2Me), 4.91 (1H, ddd, J5,6 12.0, J5,4 9.8, J5,6 4.7, 5-H), 5.10
(1H, dd, J3,4 9.8, J3,2 9.7, 3-H), 5.17 (1H, dd, J4,3 = J4,5 9.8, 4-H),
5.28 (1H, dd, J2,1 11.0, J2,3 9.7, 2-H); dC (125 MHz, CDCl3)
20.53, 20.59, 20.67, 20.79, 29.04, 42.90, 50.52, 70.15, 71.21,
72.42, 72.69, 169.87, 169.94, 170.22, 170.45, 170.63; m/z (EI)
374 (M+, 4%), 315 (5), 301 (15), 254 (9), 230 (14), 194 (8), 187
(16), 153 (27), 138 (24), 115 (12), 87 (8), 83 (15), 68 (23), 55 (11),
43 (100).
(3aS,4R,5S,7aS)-7-Iodo-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-
benzodioxole-4,5-diol 35
Crystal data for 32. C16H22O10, M = 374.3, triclinic, a =
˚
5.871(3), b = 9.395(4), c = 16.257(7) A, a = 87.59(1), b =
A solution of p-nitrobenzoate 34 (0.5 g, 1.1 mmol) in MeOH
86.43(1), c = 81.82(1)◦ U = 885.4(7) A , T = 150(2) K,
3
˚
(10 cm3) was treated with aq. K2CO3 solution (0.3 g per 0.5 cm3).
˚
◦
Mo-Ka radiation, k = 0.71073 A, space group P1 (no. 1),
The reaction mixture was heated at 40 C until all the starting
Z = 2, F(000) = 396, Dx = 1.404 g cm−3, l = 0.118 mm−1,
Bruker CCD area detector diffractometer, φ and x scan,
2.5 < 2h < 46.5◦, measured/independent reflections: 5440/4751,
direct methods solution, full matrix least squares refinement
on Fo2, anisotropic displacement parameters for non-hydrogen
atoms, all hydrogens located in difference Fourier but included at
positions determined by the geometry of the molecule using the
riding model, with isotropic vibration parameters, R1 = 0.067
for 2995 data with Fo > 4r(Fo), 479 parameters, wR2 = 0.189
material had hydrolyzed (ca. 2 h, TLC analysis). The solvent was
then removed under reduced pressure and the residue purified
by flash column chromatography (50% EtOAc in hexane) to give
trans-diol 35 as a white, crystalline solid (0.28 g, 82%); mp 135–
137 ◦C (from EtOAc–hexane); (Rf 0.44, 50% EtOAc in hexane);
[a]D −5.0 (c 0.99, MeOH); (Found: M+ 311.9866; C9H13127IO4
requires 311.9859); dH (500 MHz, CDCl3) 1.28, 1.42 [3H × 2, s,
–C(Me)2], 3.76 (1H, dd, J4,3a 7.8, J4,5 7.5, 4-H), 4.04 (1H, dd, J5,4
7.5, J5,6 1.8, 5-H), 4.18 (1H, dd, J3a,4 7.8, J3a,7a 6.2, 3a-H), 4.69
(1H, d, J7a,3a 6.2, 7a-H), 6.54 (1H, d, J6,5 1.8, 6-H); dC (125 MHz,
CDCl3), 24.97, 27.00, 70.68, 71.81, 76.26, 78.33, 94.00, 109.54,
140.98; m/z (EI) 312 (M+, 2%), 298 (5), 297 (59), 237 (6), 209
(8), 191 (5), 185 (9), 148 (12), 127 (5), 117 (17), 116 (55), 110
(42), 101 (26), 81 (15), 59 (100), 57 (6).
−3
˚
(all data), GoF = 0.98, Dqmin,max = −0.25/0.45 e A .
CCDC reference number 262886. See http://www.rsc.org/
suppdata/ob/b5/b502009c/ for crystallographic data in CIF
or other electronic format.
(1S,2R,3R,4S,5S)-5-(Hydroxymethyl)cyclohexane-1,2,3,4-
tetraol (carba-b-L-glucopyranose) 5
(3aR,4S,5S,7aS)-4-Benzoyloxy-7-iodo-2,2-dimethyl-3a,4,5,7a-
tetrahydro-1,3-benzodioxol-5-yl benzoate 36
Reduction of methyl ester 32 (0.25 g, 0.67 mmol), as described
for compound 26, furnished a sample of crude carbasugar 5.
Purification of the product by charcoal–Celite (1 : 1, v/v) column
chromatography (water → 5% EtOH in water) afforded carba-b-
L-glucopyranose 5 as a colourless syrup (0.014 g, 12%); [a]D −6.1
(c 0.70, MeOH); [lit.32 [a]D +6.7 (c 0.15, MeOH)]; (Found: M+ −
H2O 148.0034; C6H12O4 requires 148.0060); m/z (EI) 160 (M+ −
H2O, 26%), 142 (30), 112 (18), 97 (7), 82 (42), 56 (100), 43 (60),
23 (32).
trans-Diol 35 (0.1 g, 0.32 mmol) was converted to dibenzoate 36
(PhCOCl–pyridine) as a white, crystalline solid (0.16 g, 93%);
mp 108–109 ◦C (from MeOH); (Rf 0.26, 15% Et2O–hexane);
[a]D +87 (c 0.67, CHCl3); (Found C 52.75, H 4.25; C23H21127IO6
requires C 53.1, H 4.0%); dH (500 MHz, CDCl3) 1.43, 1.62 [3H ×
2, s, –C(Me)2], 4.51 (1H, dd, J3a,4 8.0, J3a,7a 5.8, 3a-H), 4.83 (1H,
d, J7a,3a 5.8, 7a-H), 5.61 (1H, dd, J5,4 8.0, J5,6 2.2, 5-H), 5.72 (1H,
dd, J4,5 = J4,3a 8.0, 4-H), 6.60 (1H, d, J6,5 2.2, 6-H), 7.37–7.43
(4H, m, Ar–H), 7.50 (2H, m, Ar–H), 7.97–8.03 (4H, m, Ar–H);
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3
1 9 6 1

View Article Online
dC (125 MHz, CDCl3), 26.74, 28.23, 71.12, 71.99, 75.29, 79.93,
97.18, 111.57, 128.77, 128.85, 129.45, 129.80, 130.23, 130.25,
130.43, 130.75, 131.18, 133.45, 133.59, 133.78, 138.79, 165.89,
166.15; m/z (EI) 520 (M+, 2%), 505 (5), 398 (30), 341 (4), 142
(37), 106 (38), 105 (100), 77 (68).
(1S,2R,3S,4R)-3-[1-(tert-Butyl)-1,1-dimethylsilyl]-5-iodo-5-
cyclohexene-1,2,4-triol 40
To a solution of compound 39 (0.2 g, 0.27 mmol) in MeOH
(20 cm3), 5% aq. NaOH solution was added (3 cm3). The
reaction mixture was stirred at room temperature until all the
starting material had hydrolysed (TLC analysis). The solvents
were evaporated and the residue purified by flash column
chromatography (60% EtOAc in hexane) to give the TBDMS
triol 40 as a colourless, viscous oil (0.09 g, 86%); (Rf 0.49,
70% EtOAc in hexane); [a]D +13 (c 0.69, MeOH); (Found: M+
386.0398; C12H23127IO4Si requires 386.0410); dH (500 MHz,
CD3OD) 0.00, 0.04 [3H × 2, s, –Si(Me)2], 0.77 [9H, s, –C(Me)3],
3.16 (1 H, dd, J2,3 10.4, J2,1 8.0, 2-H), 3.23 (1H, dd, J3,2 10.4,
J3,4 7.0, 3-H), 3.77 (1H, dd, J1,2 8.0, J1,6 2.1, 1-H), 3.91 (1H, dd,
J4,3 7.0, J4,6 1.7, 4-H), 6.12 (1H, dd, J6,1 2.1, J6,4 1.7, 6-H), dC
(125 MHz, CD3OD) −4.72, −4.70, 17.88, 25.07, 25.24, 25.41,
72.38, 72.90, 75.07, 75.42, 103.32, 140.81, m/z (EI) 386 (M+,
10%), 329 (3), 311 (6), 283 (4), 237 (5), 202 (6), 191 (10), 185
(15), 184 (48), 183 (17), 156 (19), 155 (8), 121 (26), 110 (28), 103
(32), 82 (15), 75 (100), 59 (7).
(1S,4S,5R,6S)-6-Benzoyloxy-4,5-dihydroxy-3-iodo-2-
cyclohexenyl benzoate 37
Deprotection of the acetonide group of dibenzoate 36 (0.16 g,
0.3 mmol) using the procedure described for the synthesis of
benzoate 18 gave cis-diol 37 as a colourless oil (0.125 g, 86%);
(Rf 0.23, 30% EtOAc in hexane); [a]D −23 (c 1.0, CHCl3);
(Found: M+ − H2O, 462.0021; C20H15127IO5 requires 462.0025);
dH (500 MHz, CDCl3) 4.06 (1H, dd, J5,6 8.6, J5,4 4.2, 5-H), 4.54
(1H, d, J4,5 4.2, 4-H), 5.74–5.76 (2H, m, 1-H, 6-H), 6.50 (1H,
d, J2,1 2.3, 2-H), 7.39–7.48 (6H, m, Ar–H), 7.96–8.11 (4H, m,
Ar–H); dC (125 MHz, CDCl3) 70.45, 71.91, 73.62, 76.49, 94.41,
100.46, 128.85, 129.13, 129.45, 130.01, 130.78, 131.23, 131.78,
132.67, 133.33, 133.67, 134.04, 137.97, 167.90, 167.98; m/z (EI)
462 (M+ − H2O, 34%), 353 (27), 329 (7), 316 (13), 307 (8), 281
(5), 254 (41), 249 (18), 236 (36), 231 (52), 225 (93), 212 (39), 208
(100), 207 (23), 196 (7).
Methyl (3S,4R,5R,6S)-5-[{1-(tert-butyl)-1,1-dimethylsilyl}-
oxy]-3,4,6-trihydroxy-1-cyclohexene-1-carboxylate 41
(1R,4S,5S,6S)-4,5-Di(benzoyloxy)-6-hydroxy-2-iodo-2-
cyclohexenyl 4-nitrobenzoate 38
Palladium-catalyzed carbonylation of compound 40 (0.08 g,
0.2 mmol) using the procedure mentioned earlier yielded methyl
ester 41 as a colourless, viscous oil (0.09 g, 69%); (Rf 0.40, 70%
Employing the Mitsunobu reaction conditions as described for
the synthesis of p-nitrobenzoate 19, cis-diol 37 (0.05 g, 0.1 mmol)
gave p-nitrobenzoate 38 as a white, crystalline solid (0.051 g,
80%); mp 108–111 ◦C (from EtOAc); (Rf 0.28, 20% EtOAc
in hexane); [a]D +125 (c 0.51, CHCl3); (Found: M+ 629.0259;
C27H20127INO9 requires 629.0261); dH (500 MHz, CDCl3) 4.32
(1H, dd, J6,5 10.6, J6,1 7.6, 6-H), 5.78 (1H, dd, J5,6 10.6, J5,4
8.2, 5-H), 5.91 (1H, dd, J4,5 8.7, J4,3 2.7, 4-H), 6.03 (1H, d, J1,6
7.6, 1-H), 6.68 (1H, d, J3,4 2.3, 3-H), 7.39, 7.42–7.56 (6H, m,
Ar–H), 7.98–8.34 (8H, m, Ar–H); dC (125 MHz, CDCl3) 72.20,
72.45, 73.50, 78.70, 97.80, 130.10, 130.78, 131.29, 131.34, 131.40,
131.47, 131.55, 132.45, 133.00, 133.12, 133.67, 134.11, 134.22,
134.49, 134.71, 134.77, 134.81, 135.56, 135.91, 164.96, 166.45,
167.50; m/z (EI) 629 (M+, 12%), 508 (100), 510 (5), 502 (3), 463
(4), 386 (5), 341 (4), 308 (12), 289 (13), 222 (10), 198 (7), 154 (3),
100 (9), 67 (12), 43 (5).
EtOAc in hexane); [a]D +32 (c 0.57, MeOH); (Found: M+
−
H2O, 300.0034; C14H24O5Si requires 300.0019); dH (500 MHz,
CD3OD) 0.04 [6H, s, –Si(Me)2], 0.77 [9H, s, –C(Me)3], 3.18 (1H,
dd, J4,5 10.2, J4,3 8.0, 4-H), 3.32 (1H, dd, J5,4 10.2, J5,6 7.3, 5-H),
3.60 (3H, s, –CO2Me), 3.81 (1H, dd, J3,4 8.0, J3,2 2.2, 3-H), 3.95
(1H, d, J6,5 7.3, 6-H), 6.30 (1H, d, J2,3 2.2, 2-H); dC (125 MHz,
CD3OD) −4.24, −4.22, 17.93, 25.24, 25.44, 25.83, 51.39, 70.33,
71.49, 75.52, 76.03, 103.80, 140.34, 167.13; m/z (EI) 300 (M+ −
H2O, 34%), 285 (56), 243 (79), 208 (27), 176 (34), 124 (100), 91
(81), 76 (11), 43 (65), 29 (15).
Methyl (1R,2S,3R,4R,5S)-3-[{1-(tert-butyl)-1,1-dimethylsilyl}-
oxy]-2,4,5-tri(hydroxyl)cyclohexane-1-carboxylate 42
a,b-Unsaturated methyl ester 41 (0.08 g, 0.25 mmol) was
catalytically hydrogenated using the procedure described for the
hydrogenation of compound 8 to give the saturated methyl ester
42 as a colourless syrup (0.07 g, 80%); [a]D +18 (c 0.60, MeOH);
(Found: M+ − H2O 302.0942; C14H26SiO5 requires 302.0951); dH
(500 MHz, MeOH) 0.01 [6H, s, –Si(Me)2], 0.78 [9H, s, –C(Me)3],
(1R,4S,5R,6S)-4,5-Di(benzoyloxy)-6-[{1-(tert-butyl)-1,1-
dimethyl}-oxy]-2-iodo-2-cyclohexenyl 4-nitrobenzoate 39
To a solution of p-nitrobenzoate 38 (0.13 g, 0.21 mmol) in
dry CH2Cl2 (4 cm3) containing 2,6-lutidine (0.07 g, 0.62 mmol)
was added, under a nitrogen atmosphere, TBDMSTf (0.085 g,
0.32 mmol) at 0 ◦C. After stirring the reaction mixture at 0 ◦C
(0.25 h) and then at room temperature (3 h), it was quenched
by adding 5% aq. NaHCO3 solution. The mixture was extracted
with CH2Cl2 (2 × 20 cm3), the organic extract washed with
water and dried (Na2SO4). Purification of the residue, obtained
after evaporation of CH2Cl2, by PLC (25% EtOAc in hexane)
yielded the mono-TBDMS derivative 39 as a colourless, viscous
oil (0.14 g, 93%); (Rf 0.20, 10% Et2O in hexane); [a]D +117 (c
0.61, CHCl3); (Found: M+ 742.9934; C33H34127INSiO9 requires
742.9933); dH (500 MHz, CDCl3) 0.15, 0.17 [3H × 2, s, –Si(Me)2],
0.68 [9H, s, –C(Me)3], 4.41 (1H, dd, J6,5 8.1, J6,1 7.6, 6-H), 5.82–
5.83 (2H, m, 4-H, 5-H), 6.06 (1H, d, J1,6 7.6, 1-H), 6.68 (1H,
d, J3,4 2.0, 3-H), 7.26–7.53 (6H, m, Ar–H), 7.95–8.30 (8H, m,
Ar–H); dC (125 MHz, CDCl3) −4.47, −4.45, 15.12, 24.79, 25.25,
25.35, 71.20, 72.61, 72.76, 78.55, 99.23, 123.69, 133.42, 133.54,
133.56, 133.65, 133.66, 133.67, 133.99, 134.11, 134.24, 134.25,
134.37, 134.41, 134.66, 134.70, 134.72, 134.73, 134.74 137.89,
163.63, 163.93, 165.34; m/z (EI) 743 (M+, 9%), 686 (14), 624
(27), 577 (16), 546 (12), 512 (53), 489 (17), 455 (13), 390 (17),
373 (5), 351 (80), 327 (7), 289 (14), 212 (10), 105 (100), 77 (17),
57 (15), 43 (28).
ꢀ
ꢀ
ꢀ
1.38–1.39 (1H, m, 6-H), 1.79 (1H, ddd, J6 ,1 13.1, J6 ,6 = J6 ,5 4.2,
6ꢀ-H), 2.31 (1H, ddd, J1,6 13.1, J1,2 10.0, J1,6 3.6, 1-H), 3.42 (3H, s,
ꢀ
–CO2Me), 3.03–3.04 (2H, m, 3-H, 4-H), 3.41–3.42 (2H, m, 2-H,
5-H); dC (125 MHz, CDCl3) −4.26, 19.37, 26.66–26.75, 47.59,
52.81, 74.38, 75.17, 78.26, 79.23, 175.80; m/z (EI) 302 (M+ −
H2O, 25%), 245 (34), 231 (10), 227 (24), 213 (25), 171 (19), 167
(12), 153 (10), 139 (46), 129 (18), 121 (16), 111 (19), 93 (18), 83
(13), 75 (100), 73 (43), 67 (11), 59 (18).
Methyl (1R,2S,3R,4R,5S)-3,4,5-tri[{1-(tert-butyl)-1,1-
dimethylsilyl}oxy]-2-hydroxycyclohexane-1-carboxylate 43
Using the procedure described for the synthesis of compound
39, methyl ester 42 (0.160 g, 0.5 mmol) was converted to the tri-
TBDMS derivative 43, a colourless syrup (0.250 g, 95%); [a]D
−4 (c 0.71, CHCl3); (Found: M+ 548.0084; C26H56O6Si3 requires
548.0080); dH (500 MHz, CDCl3) 0.006, 0.01, 0.012 [6H, s, 3 ×
–Si(Me)2], 0.78, 0.80, 0.81 [9H, s, 3 × –C(Me)3], 1.79–1.80 (2H,
m, J 9.2, 6-H, 6ꢀ-H), 2.60–2.61 (1H, m, 1-H), 3.59 (3H, s, –
CO2Me), 3.60–3.61 (1H, m, 3-H), 3.66–3.68 (1H, m, 4-H), 3.87–
3.89 (1H, m, J 8.1, J 2.3, 5-H), 4.13–4.14 (1H, m, J 6.0, 2-
H); dC (125 MHz, CDCl3) −4.51, −4.47, −4.39, −4.35, −4.22,
−4.11, 17.82, 17.87, 17.95, 23.45, 25.10, 25.22, 25.27, 25.56,
25.78, 25.81, 25.82, 25.98, 26.06, 40.02, 51.62, 73.36, 74.96,
1 9 6 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 9 5 3 – 1 9 6 3

View Article Online
78.59, 79.37, 174.94; m/z (EI) 548 (M+, 2%), 474 (33), 473 (74),
415 (10), 399 (14), 341 (8), 267 (20), 245 (10), 209 (5), 189 (29),
171 (5), 148 (25), 147 (84), 133 (21), 115 (12), 105 (5), 89 (18), 84
(27), 73 (100).
9 D. R. Boyd, N. D. Sharma, B. Byrne, M. V. Hand, J. F. Malone, G. N.
Sheldrake, J. Blacker and H. Dalton, J. Chem. Soc., Perkin Trans. 1,
1998, 1935.
10 D. R. Boyd, M. V. Hand, N. D. Sharma, J. Chima and H. Dalton,
J. Chem. Soc., Chem. Commun., 1991, 1630.
11 D. R. Boyd, J. Blacker, B. Byrne, M. V. Hand, S. Kelly, R. A. More
O’Ferrall, S. N. Rao, N. D. Sharma, G. N. Sheldrake and H. Dalton,
J. Chem. Soc., Chem. Commun., 1994, 313.
12 D. R. Boyd, N. D. Sharma, H. Dalton and D. A. Clarke, Chem.
Commun., 1996, 45.
13 D. R. Boyd, N. D. Sharma, C. R. O’Dowd and F. Hempenstall, Chem.
Commun., 2000, 2151.
14 M. G. Banwell, C. De Savi, D. C. R. Hockless, S. Pallich and K. G.
Watson, Synlett., 1999, S1, 885.
15 D. A. Entwistle and T. Hudlicky, Tetrahedron Lett., 1995, 36,
2591.
16 J. L. Humphreys, D. J. Lowes, K. A. Wesson and R. C. Whitehead,
Tetrahedron Lett., 2004, 45, 3429–3432.
17 D. R. Boyd, N. D. Sharma, M. V. Hand, M. R. Groocock, N. A.
Kerley, H. Dalton, J. Chima and G. N. Sheldrake, J. Chem. Soc.,
Chem. Commun., 1993, 974.
18 D. R. Boyd, N. D. Sharma, S. A. Barr, H. Dalton, J. Chima, G. M.
Whited and R. Seemayer, J. Am. Chem. Soc., 1994, 116, 1147.
19 C. C. R. Allen, D. R. Boyd, N. D. Sharma, H. Dalton, I. N.
Brannigan, N. A. Kerley, G. N. Sheldrake and S. C. Taylor, J. Chem.
Soc., Chem. Commun, 1995, 117.
(1S,2R,3R,4S,5S)-5-(Hydroxymethyl)cyclohexane-1,2,3,4-
tetraol (carba-b-L-glucopyranose) 5
Compound 43 (0.080 g, 0.15 mmol) was reduced (LiAlH4–THF)
using the procedure described for the synthesis of compound 26
to give the protected carbasugar 44 as a colourless syrup; H-
1
NMR spectral data of the crude product were consistent with
the structure. Deprotection of carbasugar 44 was carried out
without purification. To a cooled solution (0 ◦C) of carbasugar
44 (0.1 g) in dry THF (1 cm3), tetrabutylammonium fluoride so-
lution (1.0 M solution in THF, 0.75 cm3) was added. The reaction
mixture was stirred at 0 ◦C (0.5 h) and then at room temperature
(3 h). Removal ofthesolvent under reduced pressure afforded the
crude, free carbasugar which, upon purification using charcoal–
Celite (1 : 1, v/v) column chromatography (water → 10% EtOH
in water), afforded carba-b-L-glucose 5 as a white powder (0.02 g,
82%); [a]D −6.5 (c 0.50, MeOH). The spectral data of carbasugar
5 were identical to those reported in the literature.32
20 R. E. Parales, S. M. Resnick, C. L. Yu, D. R. Boyd, N. D. Sharma
and D. T. Gibson, J. Bacteriol., 2000, 184, 5495.
21 H. Akgun and T. Hudlicky, Tetrahedron. Lett., 1999, 40, 3081.
22 S. Ogawa, in Carbohydrate Mimics: Concepts and Methods, Y. Chap-
leur, ed., Wiley-VCH, Weinheim, 1998, p. 87.
Acknowledgements
We gratefully acknowledge financial support from the EC-HEA
North South Programme for Collaborative Research (NDS), the
European Social Fund (NML) and the Queenc¸o¨s University of
23 T. W. Miller, B. H. Arison and G. Albers-Schonberg, Biotechnol.
Bioeng., 1973, 15, 1075.
¨
Belfast (CROC¸ OD).
24 D. D. Schmidt, W. Frommer, B. Junge, W. Muller, W. Wingender, E.
Truscheit and D. Schafter, Naturwissenschaften, 1977, 64, 535.
25 I. Miwa, H. Hara, J. Okuda, T. Suami and S. Ogawa, Biochem. Int.,
1985, 11, 809.
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