(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

(-)- and (+)-Conduramine B-1 ((-)- and (+)-S, 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 beta-glucosides, it does not inhibit beta-glucosidases but inhibits alpha-mannosidases selectively. N-Benzylation of (-)-5 improves the potency of conduramine B-1 as alpha-mannosidase inhibitor and also generates compounds inhibiting beta-glucosidases. For instance, (-)-N-benzyl-conduramine B-1 ((-)-19a) is a competitive inhibitor of beta-glucosidase from almonds (IC50 = 32 mu M, K-i = 10 mu M) and a weak inhibitor of alpha-mannosidases from jack bean (IC50 = 171 mu M) and from almonds (IC50 = 225 mu M) whereas (-)-N-(4-phenylbenzyl)conduramine B-1 ((-)-19g) is a good inhibitor of alpha-mannosidase from jack beans (IC50 = 29 mu M, K-i = 4.8 mu M) and a weaker inhibitor of beta-glucosidase from almonds (IC50 = 32 mu M, K-i = 7.8 mu M) (Table 1).