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H
O
R
R
O
O
O
O
O
H
O
O
H
O
H
R
O
H
O
N
O
HN
H
R
O
HN
R
O
O
O
O
O
O
O
HN
O
O
R
H
O
H
N
O
H
N
O
NH
O
O
O
O
O
O
H
NH
O
O
H
R
O
O
H
O
R
O
H
O
R
O
O
R
O
R=
H
O
49
50
Scheme 14 Sugar anomeric
b
amino acid cyclic oligomers.
yielded the corresponding cyclopeptides 49 and 50 in 90 and 34 % yield
respectively (Scheme 14). NMR spectra of each compound gave only one
set of signals corresponding to the sugar residue showing rapidly inter-
changing conformers in solution. Molecular modelling of the two
cyclopeptides showed a C2 symmetry axis for 49 and a C6 symmetry axis
for 50 with possible hydrogen bonding between the NH and the sugar
ring oxygen.
3.4 Formation of C-C bond at the anomeric centre
The formation of carbon-carbon bond at the anomeric centre of exo-
glycals should be a unique route to bis C-glycosyl compounds. This type
of structure is not well documented but is of interest by providing new
templates for the elaboration of complex carbohydrate mimics such as
enzyme transition state analogues or spiro-cyclic sugar derivatives. There
are some examples of such compounds in the literature often obtained by
lengthy routes.
45
Anomeric cyclopropanation, developed by Vasella,
provided an elegant solution to this problem.
46
The reverse approach, i.e.
the cyclopropanation of anomeric double bond, was only documented
with 5,6-exo-glycals.
47
Exo-glycals have been used to access bis-C-glycosyl
derivatives using anomeric radical addition on acrylate,
48
or using the
Povarov reaction.
49
The carbene addition on the double bond of dichloro exo-glycals was
explored. Dichlorocarbene, easily obtained from chloroform in a two
phases system, was found the most ecient reagent giving tetra-
chlorocyclopropanes 51 in useful yields.
50
Reduction of the chlorine-
carbon bond was achieved using lithium aluminium hydride in THF
providing the spirocyclopropanes 52 in good yields (Scheme 15).
Cyclopropanation of activated double bond of exo-glycals 3 cannot be
carried out eciently. However, the 1,4 addition of anion was easily
achieved. Among several candidates, the anion of nitromethane was the
most ecient. Thus treatment of activated exo-glycals (erythro, gulo and
manno derivatives) with nitromethane in the presence of DBU gave an
unseparable mixture of stereoisomers, the major isomer resulting from
the attack of the double bond opposite to the 2,3-isopropylidene. The
corresponding nitro esters were obtained in excellent yields starting from
E-isomer, but lower yields were obtained with the Z-isomer. Even if
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