Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A1 and A2 Stereoisomers.

Abstract

A novel straightforward chemoenzymatic procedure for the synthesis of hyacinthacine stereoisomers based on the aldol addition of dihydroxyacetone phosphate (DHAP) to N-Cbz-prolinal under catalysis by l-rhamnulose 1-phosphate aldolase from E. coli is presented. The synthesis is complemented by a simple and effective purification protocol consisting of ion-exchange chromatography on CM-sepharose. As examples, ( )-hyacinthacine A2 [the enantiomer of (+)-hyacinthacine A2], 7-deoxy- 2-epialexine (the enantiomer of 3-epihyacinthacine A2), ent-7-deoxyalexine (the enantiomer of 7-deoxyalexine) and 2-epihyacinthacine A2 were synthesized by these procedures and characterized for the first time. These new isomers were assayed as inhibitors of glycosidases. As a result, ( )-hyacinthacine A2 demonstrated to be a good inhibitor of a-d-glucosidase from rice whereas the natural enantiomer, hyacinthacine A2, was not. Moreover, a new family of inhibitors of a-l-rhamnosidase was uncovered.