A stereoselective approach to β-L-arabino nucleoside analogues: Synthesis and cyclization of acyclic 1′,2′-syn N, O-Acetals

摘要

Reported herein is a novel and versatile strategy for the stereoselective synthesis of unnatural β-l-arabinofuranosyl nucleoside analogues from acyclic N,OTMS-acetals bearing pyrimidine and purine bases. These unusual acetals undergo a C1′ to C4′ cyclization where the OTMS of the acetal serves as the nucleophile to generate 2′-oxynucleosides with complete retention of configuration at the C1′ acetal center. N,OTMS-acetals are obtained diastereoselectively from additions of silylated nucleobases onto acyclic polyalkoxyaldehydes in the presence of MgBr _2·OEt _2. The strategy reported is addressing important synthetic challenges by providing stereoselective access to unnatural l-nucleosides starting from easily accessible pools of d-sugars and, as importantly, by allowing the formation of the sterically challenging 1′,2′-cis nucleosides. A wide variety of nucleoside analogues were synthesized in 7-8 steps from easily accessible d-xylose.