The regiospecific one-pot phosphorylation of either the 5'- or 2'-hydroxyl in 3'-deoxycytidines without protection: critical role of the base.

We report methodology which enables direct phosphorylation of 3'-deoxycytidine exclusively either at the 5'-hydroxyl or the 2'-hydroxyl. Protection of the base is not required. Standard phosphoramidochloridates in combination with pyridine and tert-butyl magnesium chloride is employed, in which the ratio of nucleoside to Grignard reagent is crucial.

Design and synthesis of spiro-cyclopentenyl and spiro-[1,3]-dithiolanyl substituted pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease.

Using the pyrrolidine-5,5-trans-lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 2b, with a spiro-cyclobutyl P1 substituent and an isopropyl carbonyl substituent at the lactam nitrogen, has an IC(50) value in the replicon cell-based assay of 3 microM.