(1S,2S,3R,6R)-6-Aminocyclohex-4-ene-1,2,3-triol (= (−)-Conduramine B-1) Is a Selective Inhibitor of α-Mannosidases. Its Inhibitory Activity Is Enhanced by N-Benzylation
✍ Scribed by Robert Łysek; Catherine Schütz; Pierre Vogel
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- German
- Weight
- 341 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
(−)‐ and (+)‐Conduramine B‐1 ((−)‐ and (+)‐5, resp.) have been derived from (+)‐ and (−)‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one (‘naked sugars’ of the first generation). Although (−)‐5 imitates the structure of β‐glucosides, it does not inhibit β‐glucosidases but inhibits α‐mannosidases selectively. N‐Benzylation of (−)‐5 improves the potency of conduramine B‐1 as α‐mannosidase inhibitor and also generates compounds inhibiting β‐glucosidases. For instance, (−)‐N‐benzyl‐conduramine B‐1 ((−)‐19a) is a competitive inhibitor of β‐glucosidase from almonds (IC~50~ = 32 μM, K~i~ = 10 μM) and a weak inhibitor of α‐mannosidases from jack bean (IC~50~ = 171 μM) and from almonds (IC~50~ = 225 μM) whereas (−)‐N‐(4‐phenylbenzyl)conduramine B‐1 ((−)‐19g) is a good inhibitor of α‐mannosidase from jack beans (IC~50~ = 29 μM, K~i~ = 4.8 μM) and a weaker inhibitor of β‐glucosidase from almonds (IC~50~ = 32 μM, K~i~ = 7.8 μM) (Table 1).