Biomedical Engineering Reference
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whose mode of action derives from impairment of bacterial cell wall synthesis [13].
The synthesis is characterized by the repeated use of sulfoxide glycosylation method
developed by Kahne and coworkers in the late 1980s [14] and by the use of Fraser-
Reid's tetrachlorophthalimide [15] protecting group as a stereodirecting and readily
cleavable protecting system for the glucosamine nitrogen. The sulfoxide method
proceeds by activation with trifluoromethanesulfonic anhydride at temperatures as
low as
78
C and is known for its ability to glycosylate even the most hindered of
alcohols such as 7
-OH of bile acids [14a,14b]. The tetrachlorophthalimido group is a
more highly crystalline version of the classical phthalimido group that directs
glycosylations
trans
to itself [16], even if it is not clear whether it functions
through neighboring group participation or simply through steric hindrance. It has
the advantage of being cleaved under milder conditions than the phthalimido group
through simple action of ethylene diamine. A further 1,2-
trans
-equatorial linkagewas
achieved in the absence of neighboring group participation by means of the nitrile
effect, a topic to which we will return later. The additive allyl dimethoxybenzene
(ADMB) repeatedly employed in this synthesis functions as a trap for the electrophilic
sulfenate ester by-products of the sulfoxide method [17].
a
12.2.
1,2-cis-EQUATORIAL GLYCOSIDES
12.2.1.
-Mannopyranosides
b
The
-mannopyranosides were long considered to be one of the most difficult classes
of glycosidic bond to access, given the need to avoid neighboring group participation
from any group at the 2-position and the need to overcome the anomeric effect, both
of which strongly favor formation of
b
-glycoside. Over the years, many methods
depending on heterogeneous promoters or indirect routes involving the more facile
b
a
-glucoside formation followed by inversion of stereochemistry at the 2-position
were developed [18], as were ingenious direct approaches based on the stereo-
selective alkylation of the
-mannopyranose hemiacetal [19], but it was not until
1997 that a direct highly stereocontrolled method was discovered [20]
(Scheme 12.3). This chemistry relies on the use of a 4,6-
O-
benzylidene acetal as
a remote stereocontrolling element that, following a long series of physical organic
studies [21], is considered to act via its ability to stabilize an intermediate glycosyl
triflate [22].
b
BnO
BnO
OBn
OBn
O
O
O
Ph
O
Ph
O
Ph
O
Ph
O
O
O
O
O
O
BnO
BnO
BnO
BnO
S
OTf
CIP
SSIP
O
Ph
TfO
TfO
Donor
ROH
Acceptor
ROH
OBn
OBn
O
O
Ph
Ph
O
O
O
O
OR
BnO
BnO
OR
β
-Mannoside
α
-Mannoside
SCHEME 12.3
Benzylidene-directed
b
-mannosylation.
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