Milbemycins, a new family of macrolide antibiotics. Structure determination of milbemycins D,E,F,G,H,J and K.

Abstract

The milbemycins, a group of potent, broad-spectrum antiparasitic and pesticidal agents, are architecturally novel antibiotic derivatives of a 16-membered macrocyclic lactone. Seven new milbemycin analogs designated milbemycins D, E, F, G, H, J and K were isolated from the fermentation broth of the mutant strain of Streptomyces hygroscopicus aureolacrimosus. The structural determination of these new components was made mainly by comparing with mass spectra, and 1H and 15C NMR spectra of milbemycin .alpha.- and .beta.-series previously published. Milbemycins D, E, F, G and H have characteristically an isopropyl side chain at C-25 which differs from the known milbemycin family bearing a methyl or ethyl group at C-25. Milbemycins J and K possess a ketone group at C-5 instead of a hydroxyl or methoxy group. Apart from X-ray crystallography, the R-configuration of the hydroxyl group at C-5 could be best explained both by application of CD [circular dichroism] allylic benzoate method to the p-N,N-dimethylaminobenzoate of milbemycin D and by comparison of the specific rotation of milbemycin D itself and its acetate with the epimeric isomers at C-5.