Development of a Generic Stereocontrolled Pathway to Fully Hydroxylated Spirocarbocyclic Nucleosides as a Prelude to RNA Targeting

ABSTRACT Osmylation of the enantiopure conjugated enones 4 and 15 proceeded predominantly or exclusively from the α-face to give the 2′,3′-diols 6 and 16. Ensuing conversion into the acetonide allowed for sequential stereocontrolled reduction with L-Selectride, and esterification with triflic anhydride was utilized to form triflates 11 and 19. The heightened electrophilicity of these intermediates made possible S N 2 displacements with several nucleobases as promoted with potassium hydride in N,N-dimethylformamide at room temperature. Suitable deprotection measures led to the targeted compounds.