Premium
Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A 1 and A 2 Stereoisomers
Author(s) -
Calveras Jordi,
Casas Josefina,
Parella Teodor,
Joglar Jesús,
Clapés Pere
Publication year - 2007
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200700168
Subject(s) - chemistry , enantiomer , aldol reaction , aldolase a , dihydroxyacetone phosphate , stereochemistry , enantioselective synthesis , stereoisomerism , regioselectivity , fructose bisphosphate aldolase , enzyme , catalysis , organic chemistry
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.