Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A₁ and A₂ Stereoisomers

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 A 2 [the enantiomer of (+)‐hyacinthacine A 2 ], 7‐deoxy‐2‐epialexine (the enantiomer of 3‐epihyacinthacine A 2 ), ent ‐7‐deoxyalexine (the enantiomer of 7‐deoxyalexine) and 2‐epihyacinthacine A 2 were synthesized by these procedures and characterized for the first time. These new isomers were assayed as inhibitors of glycosidases. As a result, (−)‐hyacinthacine A 2 demonstrated to be a good inhibitor of α‐ D ‐glucosidase from rice whereas the natural enantiomer, hyacinthacine A 2 , was not. Moreover, a new family of inhibitors of α‐ L ‐rhamnosidase was uncovered.