Angolamycin

Angolamycin (1) and two novel analogues (2 and 3) were isolated from the culture broth of a Streptomyces strain. NMR and MS analysis proved that 2 is the 18-dihydro-, while 3 is the 18-deoxo-18-dihydro derivative of angolamycin. Full experimental assignment of the 1H and the 13C NMR spectra of these compounds was obtained from 1D and 2D chemical shift correlation measurements. Compounds 2 and 3 are less potent antibiotics than angolamycin.

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A1 and 4"-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4"-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.

16-Membered epoxyenone macrolide antibiotics were reductively deepoxidized with dissolving metals such as zinc. Angolamycin and rosamicin which have a methyl substituent at C-12 in the epoxyenone structure were deepoxidized, but not isomerized further to the geometric isomers P2 and P3.