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-thiazolidinecarboxylicacid. This method could be easily extended to the synthesis of several analogs derived from optically active cyclic aminoacids. We alsopresent a putative model showing the interaction between L- and D-isomers of compound 1 in the IN active site. A sensibly lower IC50 value wasfound for (–)-1 over racemic-1 in an anti-IN assay.