Lincosaminides

Abstract

Lincomycin, C 18 H 34 N 2 O 6 S, the first lincosaminide antibiotic to which a structure was assigned, is defined chemically as methyl 6,8‐dideoxy‐6‐(1‐methyl‐ trans ‐4‐propyl‐ L ‐pyrrolidin‐2‐ylcarbonylamino)‐1‐thio‐ D ‐erythro‐ D ‐galacto‐octopyranoside. Both lincomycin and the semisynthetic clindamycin, C 18 H 33 ClN 2 O 5 S, are widely used in clinical practice. The trivial name of the sugar fragment of this antibiotic, methyl α‐thiolincosaminide, has lent itself to the other members of this family. Lincomycin has been produced by a variety of Streptomyces strains and by strain 1146 of Actinomyces roseolus. The earliest studies on the mechanism of action of lincomycin showed that lincomycin had the immediate effect on Staphylococcus aureus of complete inhibition of protein synthesis. Little effect on DNA and RNA synthesis was observed. Resistance to lincomycin is developed slowly, and leads to coresistance to macrolide, lincosaminide, and streptogramin B antibiotics. Lincomycin hydrochloride (Lincocin) is available in oral dosage forms and as a sterile solution for injection. Lincomycin has found use in the treatment of diseases of the ear, throat, nose, respiratory tissue, skin and soft tissue, bone, joint, dental, and septicemic infections caused by staphylococci, pneumonococci, and streptococci (other than enterococci). It has also been used in the treatment of diphtheria. Clindamycin, 7( S )‐7‐chloro‐7‐deoxylincomyin, also known as Cleocin, first resulted from the reaction of lincomycin and thionyl chloride; improved synthetic methods involve the reaction of lincomycin and triphenylphosphine dichloride or triphenylphosphine in carbon tetrachloride. Clindamycin is significantly more active than lincomycin against gram‐positive bacteria in vitro, and is absorbed rapidly following oral administration. Clindamycin has found use in the treatment of common infections caused by gram‐positive cocci. It is also efficacious in the treatment of anaerobic infections, including actinomycosis. Clindamycin has been shown to be active against strains of Plasmodium in animals. Cross‐resistance between lincomycin and clindamycin is complete, and co‐resistances of lincomycin also apply to clindamycin. The composition of matter patents in the United States issued to The Upjohn Company on clindamycin phosphate and hydrochloride having expired at the end of 1986 and in early 1987, respectively, these compounds have been available generically from more than two dozen companies in the United States alone.