12,34-Oxamanzamines, novel biocatalytic and natural products from manzamine producing Indo-Pacific sponges

ent-12,34-Oxamanzamines E () and F (), as well as 12,34-oxamanzamine A () were isolated from three Indo-Pacific sponges and their structures were assigned on the basis of spectroscopic data. The biocatalytic transformation of ent-8-hydroxymanzamine A () to , using Nocardia sp. ATCC 21145 and Fusarium oxysporium ATCC 7601, has also been achieved. These compounds possess a novel ring system generated through a new ether bridge formed between carbons 12 and 34 of the typical manzamine structure. Ten heterotrophic bacterial isolates, including actinomycetes and α-proteobacteria, were isolated from one of these sponges in a preliminary effort to identify a possible microbial origin for these compounds. The potent activity of the manzamines against malaria and the AIDS OI pathogen, Mycobacterium tuberculosis, is also presented.