ASYMMETRIC-SYNTHESIS OF (1'S,2'R)-CYCLOPROPYL CARBOCYCLIC NUCLEOSIDES

Enantiomeric synthesis of cyclopropyl carbocyclic nucleosides has been accomplished. The key intermediates 7 and 9 were synthesized from D-g lyceraldehyde acetonide 1, which was converted to the alpha,beta-unsat urated ester 2 and then reduced to give allylic alcohol 3a. Stereosele ctive construction of the cyclopropyl ring of 3a and 3b followed by ox idation gave acid 5, which was treated under Curtius rearrangement con ditions to obtain the urea intermediate 7. The urea intermediate was u tilized to prepare uracil 14, thymine 15, and cytosine 18 nucleosides. The purine derivatives were prepared from cyclopropylamine 9 by conde nsation with 4,6-dichloro-5-form-amidopyrimidine or 4,6-dichloro-2-ami nopyrimidine.