Studies toward the total synthesis of dideoxy lomaiviticinone

Abstract

The diazoparaquinone natural products lomaiviticin A and lomaiviticin B were isolated in 2001 from the marine actinomycete bacteria Micromonospora lomaivitiensis. Lomaiviticin A showed potent DNA-damaging and antibacterial activity. Its examination against a 24-cancer cell line panel revealed IC¬50 values in the pico to nanomolar range (IC50 = 0.007 – 72 nM). Our interest in this family of antibiotics originated in the effort to prepare dimeric (dideoxy lomaiviticinone) and monomeric analogs of lomaiviticins, which are inaccessible from nature. Chapter I of this dissertation provides an overview of current knowledge about the diazoparaquinone family of antibiotics. Chapter II describes synthetic routes to key building blocks designed for the synthesis of dideoxy lomaiviticinone. Chapters III and IV discuss two generations of strategies toward the completion of an annulation sequence with the goal of generating dideoxy lomaiviticinone.