A Stereoselective Synthesis of 4--Fluoro-methyl Carbocyclic Nucleoside Analogs

The 4' position modifications in carbocyclic nucleosides have not been investigated much as potential antiviral agents. Due to the higher ring strain and torsion of the cyclopentyl carbocyclic ring, it is not easy to carry out the modification at the 4' position. Therefore, there is a need for a procedure that may tackle the synthesis of 4' position substituted carbocyclic pentyl ring. In this communication, a stereoselective synthesis of 4'-alpha-fluoro-methyl carbocyclic nucleosides has been reported. A stereoselective synthesis of the 4-alpha-fluoro-methyl carbocyclic sugar moiety (16) was carried out via carbocyclic ketone 1. The oxidation of the 5-methyl hydroxy of 9 followed by the aldol condensation gave a diol 11, which via selective protection followed by selective fluorination, yielded a MOM-protected 4-alpha-fluoro-methyl carbocyclic ring (16). Compound 16 served as a key intermediate for the synthesis of purines (21&24) and pyrimidine (28&31) nucleosides. The described synthesis may be utilized to construct the various 4' position modified carbocyclic nucleos(t)ides for an elaborated structure-activity relationship (SAR) as an antiviral and anticancer agent.