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The development of a convergent and highly stereoselective synthesis of an HCV NS3/4a protease inhibitor possessing a unique spirocyclic and macrocyclic architecture is described. A late-stage spirocyclization strategy both enabled rapid structure-activity relationship studies in the drug discovery phase and simultaneously served as the basis for the large scale drug candidate preparation for clinical use. Also reported is the discovery of a novel InCl3-catalyzed carbonyl reduction with household aluminum foil or zinc powder as the terminal reductant. [ABSTRACT FROM AUTHOR]

Abstract: A novel and efficient synthesis of a range of racemic and enantioenriched N-substituted-4-substituted isothiazolidine-1,1-dioxides from epoxides and sulfonamides is described. The critical choice of the activating group for the cyclization event is discussed. The application of this methodology to the synthesis of N-substituted-4,5-disubstituted derivatives is also described. [Copyright &y& Elsevier]

A highly diastereoselective bifunctional organocatalyst controlled Michael addition, a nitro-Mannich/lactamization cascade, a furan N-acyliminium cyclisation, a sequential alkyne RCM/syn-reduction and an alkene RCM has allowed a 19 step, highly stereoselective synthesis of (−)-nakadomarin A. [ABSTRACT FROM AUTHOR]

Functionalised hydroxylamine derivatives of (S)-prolinol prepared by a Cope elimination have been found to undergo oxidation to the nitrone either in the presence of air or a catalytic quantity of TPAP. These undergo intramolecular cycloaddition to give tricyclic isoxazolidines with high diastereoselectivity. [Copyright &y& Elsevier]