E. J. Eisenbraun

Macrolide antibiotics—VIII : The absolute configuration of certain centers in neomethymycin, erythromycin and related antibiotics☆

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.