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(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

Laboratoire de glycochimie et de synthèse asymétrique, Ecole Polytechnique Fédérale de Lausanne, BCH, CH-1015 Lausanne-Dorigny (tel. 021 693 93 71; fax 021 693 93 75)
Helvetica Chimica Acta (Impact Factor: 1.38). 10/2005; 88(10):2788 - 2811. DOI:10.1002/hlca.200590220

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 (IC50 = 32 μM, Ki = 10 μM) and a weak inhibitor of α-mannosidases from jack bean (IC50 = 171 μM) and from almonds (IC50 = 225 μM) whereas (−)-N-(4-phenylbenzyl)conduramine B-1 ((−)-19g) is a good inhibitor of α-mannosidase from jack beans (IC50 = 29 μM, Ki = 4.8 μM) and a weaker inhibitor of β-glucosidase from almonds (IC50 = 32 μM, Ki = 7.8 μM) (Table 1).

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