From Sugars to Sugar Mimics: Stereoselective synthesis of aminocyclopentanols as glycosidase inhibitors

The mechanism of enzymatic cleavage of glycosides has been continuously under debate and design of new glycosidase inhibitors has been based on structural similarity of putative intermediates or transition states. Recently the aminocyclopentanols have drawn considerable attention as potent glycosidase inhibitors. Aminocyclopentanols having a substitution pattern similar to common carbohydrates, and with the amino group next to the side chain, has been considered as anomer selective glycosidase inhibitors,1 since the configuration at the carbon having the amino substituent might be mimicking either the  or anomer of a substrate. We have syntesised a range of aminocyclopantanols with the general structures 3 and 4, starting from the bicyclic cyclopentane-lactones 1 or 2, which are readily available from bromodeoxyaldonolactones by a radical induced carbocyclisation.2 The synthesis of the aminocyclopentanols and their inhibitory properties will be presented. 1: (a) M. Kleban, P. Hilgers, J. N. Greul, R. D. Kugler, J. Li, S. Picasso, P. Vogel, V. Jäger, CHEMBIOCHEM, 2001, 5, 365. (b) J.N. Greul, M. Kleban, B. Schneider, S. Picasso, V. Jäger, CHEMBIOCHEM, 2001, 5, 368. (b) A. Blaser, J.-L. Reymond, Helv. Chim. Acta, 2001, 84, 2119; L. G. Dickson, E. Leroy, J.-L. Reymond, Org. Biomol. Chem., 2004, 2, 1217. 2: Johansen, S. K.; Lundt, I. J. Chem. Soc., Perkin Trans. 1, 1999