One-pot synthesis of cyclic nitrones and their conversion to pyrrolizidines: 7a-epi-crotanecine inhibits alpha-mannosidases

Abstract

[reaction: see text] A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. Its efficiency relies on the condensation of unprotected hydroxylamine with readily available lactols and on the chemoselectivity of the subsequent esterification with methanesulfonyl chloride. The targeted enantiomerically pure pyrroline N-oxides are versatile synthetic intermediates: one of the nitrones so-obtained has been converted into new polyhydroxypyrrolizidines, analogues of the alkaloids rosmarinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.