Semisynthetic derivatives of madurahydroxylactone and their antibacterial activities.

Madurahydroxylactone is a secondary metabolite from Nonomuria rubra (former Actinomadura rubra) with in vitro activity against gram-positive bacteria and belongs to the family of benzo[a]naphthacenequinones. A series of derivatives of madurahydroxylactone were synthesized to investigate the effect on the antibacterial activity. Reaction with alcohols and amines gave cyclic acetals or aminals derived from the lactone form, whereas other amino reagents like hydroxylamines and acyl or sulfonyl hydrazides led to the corresponding imine derivatives of the aldehyde. Hydrazine, alkyl and aryl hydrazines react with madurahydroxylactone under cyclization to give compounds of the new heterocyclic basic structure naphthaceno[1,2-g]phthalazine. Some new compounds strongly inhibit gram-positive bacteria, in part stronger than the parent compound.