Concise synthesis of bicyclic iminosugars via reductive functionalization of sugar-derived lactams and subsequent RCM reaction

Abstract

An efficient method for the synthesis of bicyclic iminosugars has been developed. The strategy is based on the partial reduction of sugar-derived lactams by Schwartz's reagent and tandem stereoselective nucleophile addition dictated by Woerpel's model which affords polyhydroxylated cyclic amines as key intermediates. Introduction of a vinyl or allyl group to the iminosugar produces diene derivatives that can be subjected to the ring-closing metathesis reaction (RCM) to furnish polyhydroxylated pyrrolizidine, indolizidine and quinozilidine derivatives in good to excellent yields. This sequence of reactions has been applied to the formal synthesis of hyacinthacine A₂, a polyhydroxylated pyrrolizidine alkaloid.