Stereoselective Synthesis of 4'-.ALPHA.-Alkylcarbovir Derivatives Based on an Asymmetric Synthesis or Chemoenzymatic Procedure.

Abstract

Stereoselective synthesis of 4'-α-alkylcarbovir derivatives 4 was described based on asymmetric synthesis or a chemoenzymatic procedure. The asymmetric alkylation of chiral acetal 7 gave the alkylated enol ethers 9a-c possessing a chiral quaternary carbon. The key carbocyclic intermediates 14a-c were synthesized from 9a-c via eleven-steps. Coupling of 14a-c with 2-amino-6-chloropurine followed by desilylation and subsequent hydrolysis afforded the target compounds 4a-c in moderate yield. The optically active cyclopentene intermediates 5a-c and 6a-c were also prepared by enzymatic resolution of (±)-5a-c and (±)-6a-c, respectively.