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Lac
Lac
Lac
O
O
O
OH
X
O
N
HO
X
HO
N
N
N
N
OH
N
N
170
171
O
N
HO
N
HO
HO
O
O
HO
OH
OH
Lac
O
Lac
O
Lac
X
X
Lac
O
N
O
N
N
Lac
N
X
N
O
N
HO
O
X
Lac
HO
N
O
HO
O
N
N
HO
O
N
X
Lac
OH
N
N
172
X
O
HO
O
N
N
HO
N
N
HO
O
O
N
X
N
HO
HO
short linker X = OCH
2
n = 0
medium linker X = O n = 2
long linker X = O
O
N
O
N
HO
N
n = 5
173
HO
SCHEME 5.38
Multilactosides on carbohydrate scaffolds with different spacer length.
Urinary tract infections caused by uropathogenic
Escherichia coli
presents a
serious communal and nosocomial health problem. The disease is initiated by the
adhesion of bacteria to bladder cells, by means of the fimbriae, which express a
mannose-binding adhesin called FimH. Heptyl
-D-mannoside (HM) is a strong
inhibitor of this lectin at nanomolar concentrations. It was shown that this compound
prevents the adhesion of type 1-piliated
E. coli
and reduces bacteria levels in a murine
cystitis model [62]. A variety of multimeric heptyl mannosides (cf.
174
) with valen-
cies ranging from one to four were synthesized using the strategy described above
(Scheme 5.39). Biological evaluation of these multimannosides showed remarkable
cluster effects in the bladder-binding inhibition assay [63].
As a continuation of our work, we envisaged a new set of multivalent HM ligands
based on carbohydrate cores with structural valencies that range from 1 to 7 [64]. The
strategy used to construct the regular hydrophilic structures involved the repetition of
a critical glucoside fragment. Controlled acidic opening of a suitable functionalized
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