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

Abstract magnified image 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 the 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 the parent antibiotic, whilst the hydrophilic analogues were inactive.