Enantiomeric Synthesis of l-(or 1‘R,2‘S)-Carbocyclic Cyclopropyl Nucleosides

Abstract

The enantiomeric synthesis of carbocyclic cyclopropyl L-nucleosides has been accomplished from L-gulonic gamma-lactone. The key intermediate 3 was stereoselectively synthesized by DIBAL-H reduction and silyl protection followed by cyclopropanation from ester 2, which was in turn prepared from L-gulonic gamma-lactone (1) in five steps. Desilylation of cyclopropyl intermediate 3 gave alcohol 4, which was then converted to the urea derivative 5 and cyclopropylamine 7 by Curtius rearrangement of an acyl azide. The urea intermediate 5 was utilized to prepare thymine 10, uracil 11, and cytosine 14 derivatives. The hypoxanthine, adenine, and guanine nucleosides 21, 22, and 24 were synthesized from the amino intermediate 7.