An approach to the stereo-controlled synthesis of polycyclic derivatives of l-4-thiazolidinecarboxylic acid active against HIV-1 integrase

Herein, we describe a new strategy for the preparation of thiazolothiazepine-based inhibitors of human immunodeficiency virus type-1 integrase (IN). The present method allows facile preparation of the title compounds in a single enantiomeric form starting from l-4-thiazolidinecarboxylic acid. This method could be easily extended to the synthesis of several analogs derived from optically active cyclic aminoacids. We also present a putative model showing the interaction between l- and d-isomers of compound 1 in the IN active site. A sensibly lower IC50 value was found for (–)-1 over racemic-1 in an anti-IN assay.

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