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An efficient enantioselective synthesisof the chiral polycycliccholesteryl ester transfer protein (CETP) inhibitor 1has been developed. The synthesis was rendered practical for largescale via the development of a modified Hantzsch-type reaction toprepare the sterically hindered pyridine ring, enantioselective hydrogenationof hindered ketone 6utilizing novel BIBOP-amino-pyridinederived Ru complex, efficient ICl promoted lactone formation, anda BF3mediated hydrogenation process for diastereoselectivelactol reduction. This efficient route was successfully scaled toproduce multikilogram quantities of challenging CETP drug candidate 1. [ABSTRACT FROM AUTHOR]

Presents the synthesis of the Wittig reagent [(diethoxyphosphinyl)methylidene]triphenylphosphorane using its phosphonium triflate salt. Treatment of the reagent with various aldehydes and an activated ketone; Formation of cis and trans isomers; Hydrogenation of alpha, beta-unsaturated esters.

S-Alkyl,S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts)react with Grignard reagents to give sulfides in good yields. TheS-alkyl Bunte salts are prepared from odorless sodium thiosulfateby an SN2 reaction with alkyl halides. A Cu-catalyzed couplingof sodium thiosulfate with aryl and vinyl halides was developed toaccess S-aryl and S-vinyl Bunte salts. The reaction is amenable toa broad structural array of Bunte salts and Grignard reagents. Importantly,this route to sulfides avoids the use of malodorous thiol startingmaterials or byproducts. [ABSTRACT FROM AUTHOR]

A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce >400 kg of cyclized product. [ABSTRACT FROM AUTHOR]