Chemoenzymatic synthesis and inhibitory activities of hyacinthacines A(1) and A(2) stereoisomers

• Published in: Advanced synthesis & catalysis Vol. 349; no. 10; pp. 1661 - 1666
• Main Authors: Calveras, Jordi, Casas, Josefina, Parella, Teodor, Joglar, Jesus, Clapes, Pere
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.07.2007
• Subjects: Chemistry; Chemistry, Applied; Chemistry, Organic; Physical Sciences; Science & Technology; aldol reaction; ALDOL ADDITIONS; MECHANISM; PYRROLIZIDINE ALKALOIDS; CRYSTAL-STRUCTURE; AUSTRALINE; hyacinthacines; POLYHYDROXYLATED PYRROLIZIDINES; GLYCOSIDASE INHIBITORS; DIHYDROXYACETONE PHOSPHATE; aldolases; polyhydroxylated pyrrolizidine alkaloids; CHEMOTHERAPEUTIC VALUE; amino aldehydes; EMULSION SYSTEMS
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.200700168

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 alpha-D-glucosidase from rice whereas the natural enantiomer, hyacinthacine A(2), was not. Moreover, a new family of inhibitors of alpha-L-rhamnosidase was uncovered.