Anthracycline Antibiotics — Structure and Antitumor Activity —

Abstract

Our efforts toward the drug development of new potent antitumor anthracycline antibiotic Aclacinomycin A have been extended to the studies on biogenesis, structure-activity relationships and microbial and chemical transformations to produce more active and less toxic compounds than adriamycin. Since 1973 we have produced about 100 compounds: aclacinomycins, 2-hydroxyaclaci-nomycins, 13-methylaclacinomycins, 4-O-methylaclacinomycins, 11-hydroxyaclacinomycins, 4'“-dehydrorhodomycin Y, 11-hydroxycinerubin A, rhodirubins, roseorubicins, baumycins, 4-hydroxybaumycinols, feudomycins, 1-hydroxydaunorubicinol, trisarubicinol, 4“’-aminoaclacinomycin derivatives, cinerulosyl-2-deoxyfucosylrhodosaminyldaunomycinone derivatives by fermentation, by microbial glycosidation and by chemical modification. The biosynthetic pathways that transform the hypothetical decaketide precursors of anthracyclinones to the appropriate end products were elucidated on the basis of the chemical structures of anthracyclines newly produced by feeding presumptive biosynthetic intermediates to mutants blocked in the biosynthesis of parent metabolites. Outline of fermentation and purification, structures of anthracycline antibiotics produced by microorgnisms, biosynthesis of anthracyclinones, biological activity and its relationships to chemical structure were reviewed. © 1982, The Society of Synthetic Organic Chemistry, Japan. All rights reserved.