UC San Diego

Natural products (secondary metabolites) are one the most important sources of novel organic chemical scaffolds for drug discovery and for the synthetic chemists. However, over the past two decades, there has been a general consensus that the discovery of novel secondary metabolites requires new strategies as mostly known compounds are isolated today. This thesis discusses two different strategies for the discovery of natural products from a new group of actinomycetes. One is the phylogenetic approach to new marine taxa of actinomycetes of the clade MAR 4. The other is the use of new bioassays to isolate new secondary metabolites from microbial cultures.

Chapter I introduces the hypothesis in which this thesis research was performed. Chapter II is a review of terpenoids and meroterpenoids in actinomycetes. Chapters III, IV and V discuss the discovery of new secondary xviii metabolites from actinomycete clade MAR 4, based upon a phylogenetic approach to this new group. It includes the nitropyrrolins A-C (97-99), the marinophenazines A and B (105, 106) and streptoquinone (111). Chapter VI provides an example of the utilization of a new chemopreventive bioassay, inhibition of NF-κB, which was used to obtain a new bioactive meroterpenoid, naphthomarine (112). Chapter VII provides concluding remarks about this thesis research.