Hydroxylation of the N-oxide of erythromycin A 8, 9-anhydro-6
9-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-6
9-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.
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