Unified syntheses of cavicularin and riccardin C: addressing the synthesis of an arene adopting a boat configuration.

Concise syntheses of the natural products cavicularin (ten steps) and riccardin C (seven steps) are reported. Key features of the new synthetic route are a convergent strategy to assemble acyclic precursors and a sequence of regioselective reduction and halogenation steps to facilitate Wittig macrocyclisation and transannular ring contraction reactions.

Asymmetric synthesis of an N-acylpyrrolidine for inhibition of HCV polymerase.

A practical asymmetric synthesis of a highly substituted N-acylpyrrolidine on multi-kilogram scale is described. The key step in the construction of the three stereocenters is a [3+2] cycloaddition of methyl acrylate and an imino ester prepared from l-leucine t-butyl ester hydrochloride and 2-thiazolecarboxaldehyde. The cycloaddition features novel asymmetric catalysis via a complex of silver acetate and a cinchona alkaloid, particularly hydroquinine, with complete diastereomeric control and up to 87% enantiomeric control.

Optimization of novel acyl pyrrolidine inhibitors of hepatitis C virus RNA-dependent RNA polymerase leading to a development candidate.

Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties.

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.