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HO
HO
HO
HO
OH
HO
OH
OH
N
HO
N
HO
N
OH
HO
N
5
N
N
N
5
N
5
N
HO
OH
N
N
N
N
HO
OH
N
N
N
OH
O
O
HO
HO
N
5
O
O
OH
5
O
O
O
O
N
N
N
N
N
O
O
N
OH
HO
O
O
O
OH
N
5
OH
H
HO
N
HO
O
OH
OH
N
N
O
O
5
N
N
N
HO
8
N
N
HO
N
O
O
O
O
N
O
O
HO
OR
5
N
OH
O
O
O
N
HO
OH
HO
N
N
O
5
N
OH
HO
N
N
N
N
O
HO OH
O
5
N
N
N
N
N
N
N
N
OH
N
HO
N
OH
OH
OH
5
N
5
HO
N
N
8
HO
7
HO
HO
HO OH
OH
OH
OH
OH
OH
118
117
FIGURE 6.10
High-valency C
60
fullerene and
-cyclodextrin-scaffolded click clusters
exposing 1-deoxynojirimycin motifs.
The above result prompted a collaborative research by the groups of Nieren-
garten, Compain, and Ortiz Mellet to prepare high-valency click clusters exposing
DNJ motifs based on C
60
fullerene (i.e.,
117
) (Fig. 6.10) [185] and
-cyclodextrin
scaffolds (e.g.,
118
) (Fig. 6.10) [186]. Amazing increases in the inhibition potency
against yeast
-mannosidase, over 600-fold per DNJ unit in the case of the tetradeca-
conjugate
118
, were achieved. Although the biological significance of multivalency
in glycosidase inhibition is still unclear, this preliminary data represent a proof of
concept and warrants further research in that direction. Click chemistry will be—with
no doubt—instrumental for those channels.
REFERENCES
1. Reynolds, M.; Perez, S.
C. R. Chimie.
2011
,
14
, 74-95.
2. Mammen, M.; Choi, S. K.; Whitesides, G. M.
Angew. Chem. Int. Ed.
1998
,
37
, 2754-
2794.
3. Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E.
Curr. Opin. Chem. Biol.
2000
,
4
, 696-703.
4. Lundquist, J. J.; Toone, E. J.
Chem. Rev.
2002
,
102
, 555-578.
5. Kolb, H. C.; Sharpless, K. B.
Drug Discov. Today.
2003
,
8
, 1128-1137.
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