Enantioselective synthesis of new analogues of neplanocin A.

An efficient synthesis of analogues of (-)-aristeromycin (1) and (-)-neplanocin A (2) has been developed in an enantioselective and stereocontrolled manner by chemicoenzymatic strategy. The symmetric unsaturated dimethyl ester (3) was quantitatively hydrolyzed with pig liver esterase to yield a half ester (4). Decarboxylative ozonolysis followed by chemical transformation afforded versatile chiral intermediates, cyclopentylamine (7) and cyclopentenylamine (9), which were converted to carbocyclic analogues of 5-aminoimidazole-4-carboxamide riboside (16), (18), uridine (21), cytidine (23), and guanosine (25). The cytidine analogue (23) was found most active against KB cells in culture.