Enhancing marine natural product structural diversity and bioactivity through semisynthesis and biocatalysis.

Abstract

In the last several decades the plants, animals and microbes from the marine environment have revealed a portion of what is clearly a tremendous resource for structurally diverse and bioactive secondary metabolites. Many of these extraordinarily sophisticated and bioactive natural products can be isolated in significant quantities without great difficulty. As a result these readily available bioactive natural products provide valuable starting materials for the rational generation of libraries of compounds prepared through semisynthesis and biocatalysis. A review of our work using marine natural products to generate rationally designed compound libraries and their biological activity against infectious diseases, cancer and neurological targets is presented. The marine natural products utilized to date as starting materials consist of compounds from a variety of structural classes and include: aureol, puupehenone, sarcophine, palinurin, and the manzamine alkaloids. The possibility to generate diverse bioactive products beginning with a marine natural product scaffold is a direct result of improvements made in the technologies to harvest samples from the ocean, purify and characterize complex natural products quickly and complete chemical reactions and biotransformations in parallel. As a result the vast resources of the ocean can now be utilized routinely to design and produce countless products to be evaluated as part of drug discovery and development programs.