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 α-D-glucosidase from rice whereas the natural enantiomer, hyacinthacine A2, was not. Moreover, a new family of inhibitors of α-L-rhamnosidase was uncovered. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
- Aldol reaction
- Amino aldehydes
- Polyhydroxylated pyrrolizidine alkaloids