Synthesis and Bioactivity of Lincomycin-2-Phosphate

Tritylation of 3,4-O-anisylidene lincomycin (II) was found to give 7-O-trityl-3,4-O-anisplidene lincomycin (III), a key intermediate in the synthesis of lincomycin-2-monoesters. The structure of III was established by NMR. Phosphorylation of III with POCls in pyridine gave the resulting dichlorophosphate IV which after hydrolysis and treatment with 80% aqueous acetic acid (100°, 30 min.) gave lincomycin-2-phosphate (V). The water-soluble ester V is inactive in the plate antibacterial assay using S. lutea, although in uiuo V is as active as the parent compound lincomycin (I) in mice infected with S. aureus. V gave slightly higher blood levels than the parent compound I upon oral administration in dogs. The taste of V is less bitter than I.