Synthesis and Evaluation of S- and C(1)-Substituted Analogues of Lincomycin

New thioglycosides and C(1)-alkylated thioglycosides (S-ulosides) of lincomycin were synthesized. and their antibiotic activities were determined. The S-aryl and S-arylalkyl analogues 11a- 11i were obtained by S-glycosylation of the sulfoxides 7 with arenethiols, or by S-alkylation of the thiol 14 with alkyl bromides. Lincomycin derivatives 27, 32a, 32b, 38a, 38b, 44, and 47 were prepared via Henry reaction or Michael addition of tire lincosamine-derived 1-deoxy-1-nitropyranoses 22. The S-alkyl derivatives showed a similar activity and specificity as lincomycin. Lipophilic S-uloside analogues were two- to fourfold less active than tire parent antibiotic, whilst the hydrophilic analogues were inactive.