Synthesis and antibacterial activity of novel lincomycin derivatives. II. Exploring (7S)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives.

The synthesis and antibacterial activity of (7S)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives are described. These derivatives were mainly prepared by the Mitsunobu reaction of 2,3,4-tris-O-(trimethylsilyl)lincomycin and the corresponding thiols. Exploring structure-activity relationships of the substituent at the 5 position of a thiadiazole ring revealed that compounds with the ortho substituted phenyl group showed improved antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene compared with the reported compound (1) that had an unsubstituted benzene ring.