Codinaeopsin, an antimalarial fungal polyketide

Abstract

A new tryptophan-polyketide hybrid, codinaeopsin, was isolated from an endophytic fungus collected in Costa Rica. The structure of codinaeopsin, which was deduced from NMR and mass spectral data, contains an unusual heterocyclic unit linking indole and decalin fragments. Codinaeopsin is active against Plasmodium falciparum, the causative agent of the most lethal form of malaria (IC50 = 2.3 microg/mL or 4.7 microM).

Figure 1

Select COSY and HMBC correlations observed in codinaeopsin

Figure 2

Proposed biosynthesis of codinaeopsin. Completed structure shows labeling patterns observed in feeding experiments. PKS, polyketide synthase; SAM, S-adenosyl methionine; NRPS, nonribosomal peptide synthase (condensation-adenylation-thiolation).

Scheme 1