Enantiomeric Synthesis of L-(or 1'R,2'S)-Carbocyclic Cyclopropyl Nucleosides.
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.
Lee
Mi Gyoung
MG
Department of Medicinal Chemistry, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, and College of Pharmacy, Seoul National University, Seoul, Korea.
Du
Jin Fa
JF
Chun
Moon Woon
MW
Chu
Chung K.
CK