CHEMICAL MODIFICATION OF ERYTHROMYCINS

II. 8-HYDROXYERYTHROMYCIN A

Abstract

Hydroxylation of the N-oxide of erythromycin A 8, 9-anhydro-6⁹-hemiketal (2) with m-chloroperbenzoic acid in methanol afforded the N-oxide of 8-hydroxyerythromycin A methyl ⁹6-ketal (3); reduction of the N-oxide group yielded the methyl ⁹6-ketal of 8-hydroxyerythromycin A (4). In slightly acid medium, compound 4 readily was hydrolysed to yield 8-hydroxyerythromycin A (6). The same compound 6 was obtained by hydroxylating the double bond of the 8, 9-anhydro-6⁹-hemiketal of erythromycin A (1) with m-chloroperbenzoic acid in a mixture of ethyl acetate and water and reducing the N-oxide formed. The structure of ihe new semisynthetic antibiotic 6 was established by physicochemical methods. Compound 6 is half as active in vitro against Bacillus pumilus as the parent antibiotic, i.e. it assays 500 μg/mg in erythromycin A units (cylinder method). However its stability against acids is 500-600 times greater. In solutions compound 6 is in a ketone-hemiketal equilibrium.