Synthetic studies on biologically active natural products by a chemicoenzymatic approach: Enantioselective synthesis of C- and N-nucleosides, showdomycin, 6-azapseudouridine and cordycepin

Abstract

An efficient synthesis of C- and N-nucleosides has been developed in an enantioselective and stereocontrolled manner starting from Diels-Alder adduct of furan and dimethyl acetylenedicarboxylate by chemicoenzymatic strategy. The symmetric unsaturated dimethyl esters 2 and 3 were almost quantitatively hydrolysed with pig liver esterase to yield half-esters 4 and 5 with reasonably high optical yields. Decarboxylative ozonolysis of the chiral half-esters 4 followed by chemical transformation afforded methyl L -riboside 12, but after the enantiomer conversion ( 4 to 13 and 5 to 28) the methyl D -riboside ( 17), ( + )-showdomycin ( 22), and ( − )-6-azapseudouridine ( 27), were obtained from 13, and ( − )-cordycepin ( 32) was obtained from 28.