Biomedical Engineering Reference
In-Depth Information
OH
β
O
HO
OR'
O
OR'
O
OH
α
O
OH
O
OH
OH
O
O
O
O
OR'
OR
O
HO
OH
OR'
O
OH
SCHEME 12.43
General structure of the
M
.
tuberculosis
polyarabinan termini.
modulating the host's immune system. Because humans do not produce arabinofur-
anoside-containing bioconjugates, the enzymes involved in the biosynthesis process
of such glycoconjugates are of great interest as targets for drug action [127]. In
particular, the major structural components of the cell wall of
Mycobacterium
tuberculosis
are two polysaccharides, an arabinogalactan (AG) and a lipoarabino-
mannan (LAM), which contain a common arabinan domain made up of
D
-arabino-
furanoside residues. At the termini of this polyarabinan is a branched structure with
two
-
D
-arabinofuranoside residues (Scheme 12.43).
Synthetically,
b
-arabinofuranosides present essentially the same challenge as
b
-mannopyranosides and necessitate the avoidance of any type of participation from
the 2-position in the course of their synthesis. In view of the considerable success of
4,6-
O-
benzylidene acetals in directing mannopyranoside synthesis, it is not surpris-
ing that a number of groups turned their attention to the development of methods
employing related functionality spanning 3- and 5-positions of the furanosyl donor.
b
12.7.1. Cyclically Constrained Donors
On the basis of an analysis of the conformation of the expected oxocarbenium ion
intermediate, Ito and coworkers introduced a donor with an eight-membered ring
spanning
O-
3and
O-
5 affording good to excellent
-selectivities (Scheme 12.44) [128].
In the furanoside series, 3,5-
O-
benzylidene acetals have been described only
rarely and indeed considerable efforts were required to prepare such derivatives of an
arabinofuranosyl thioglycoside, which, moreover, proved to be relatively unstable
b
OBn
BnO
O
OBn
O
OH
BnO
BnO
NIS, AgOTf
CH
2
Cl
2
, -40°C
BnO
O
O
O
O
O
Si
Si
STol
OBn
93%
O
O
Si
O
Si
O
OBn
(α/β
= 1:12.5)
β
O
(
i
-Pr)
2
Si
O
(
i
-Pr)
2
Si
O
O
BnO
H
H
α
SCHEME 12.44
Ito's cyclic disiloxane-protected donor.
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