Common Degradation Products Research Articles

Macrolide antibiotics—VII : The structure of neomethymycin

Degradation experiments are described which establish rigorously structure (II) for neomethymycin (C 25H 43NO 7). This antibiotic belongs, therefore, to the macrolide group and differs from methymycin (I) only in the location of one hydroxyl group, which results in marked changes in chemical behavior. The two antibiotics appear to have the same absolute configuration at the relevant asymmetric centers as inferred by the isolation of a common degradation product and the general similarity of certain rotatory dispersion curves. The position of the hydroxyl group at C-12 in neomethymycin is noteworthy from a biogenetic standpoint.

Macrolide antibiotics—VIII

Abstract Neomethymycin (I) has been transformed into “anhydro cyclo neomethynolide” (V) which could be degraded via (−)-α-methyllevulinic acid to (−)-α-methylsuccinic acid, thus establishing the absolute configuration of positions 4 and 6 in the lactonic acid (XIII). This acid is a common degradation product of methymycin, neomethymycin, pikromycin and narbomycin and there is thus available a standard of absolute configuration for these macrolide antibiotics. By a different sequence of reactions, erythromycin (XXIII) has been converted into (+)-α-methyllevulinic acid and (+)-α-methylsuccinic acid. Coupled with earlier results reported in the literature, it is now possible to assign absolute configurations to positions 10 (R) and 8 (R) of erythromycin and this applies most likely also to positions 4 (R) and 2 (S). Attention is called to the biogenetic significance of these observations.