Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 2. Synthesis of 7(S)-7-deoxy-7-(4-morpholinocarbonylphenylthio)lincomycin and its 3-dimensional analysis with rRNA.

Lincomycin derivatives, which possess a hetero ring at the C-7 position via sulfur atom, were synthesized by three types of reactions: (1) Mitsunobu reaction of 2,3,4-tris-O-(trimethylsiliyl)lincomycin (1) with the corresponding thiol, (2) SN2 reaction of 7-O-methanesulfonyl-2,3,4-tris-O-(trimethylsiliyl)lincomycin (2) with the corresponding thiol and (3) Pd-catalyzed cross-coupling reaction of 7-deoxy-7-epi-7-mercaptolincomycin (35) with the corresponding aryl halides. As a result, compound 28 had potent antibacterial activities against major pathogens, which caused respiratory infections, even compared with clindamycin. On the other hand, compound 38 showed most potent activities against a variety of Streptococcus pneumoniae with erm gene.