Synthesis of neplanocin a analog with 2′′-"up"-C-methyl substituent as potential anti-HCV Agent

Abstract

2′-β-C-Methylneplanocin A (3) was synthesized via 2-β-C-methylribonolactone, prepared by a modified Whistler and BeMiller's method developed by our laboratory, as potential anti-HCV agent. Reduction of 14 with Dibal-H afforded 26 in a good yield with a trace of 25, whereas a Luche reduction gave 26/25 = 4/1 mixture. Several attempts were made to chemoselectively remove TBS group in the presence of TBDPS group and treatment with both PPTS and TsOH showed the best result. Condensation of 26 with 6-chloropurine under Mitsunobu conditions produced an SN2 product 27 along with an SN2′ product 28.