| Diazobenzofluorene natural products are a unique class of compounds that contain a diazo moiety---a functionality sparsely found in nature. This family of molecules is comprised of the monomeric kinamycins and dimeric lomaiviticins, both of which have demonstrated potent antibacterial and anticancer activity. Synthetic studies will allow larger access to better understand the properties of these important natural products. FL-120B' was targeted to establish a synthetic route to epoxide-containing diazobenzofluorenes, which may serve as precursors to the lomaiviticins.;The general strategy towards FL-120B' follows our group's previous synthesis of kinamycin C. In addition to these prior efforts, an efficient and scalable synthesis of a chiral epoxide building block was established. Furthermore, Stille cross coupling and intramolecular Friedel-Crafts acylation provided the tetracyclic carbon framework of FL-120B'. The successful outcome of the Friedel-Crafts cyclization was found to be temperature and substrate dependent, in which five carboxylic acid intermediates---differing in protecting groups---were screened. In attempts to perform a photo-Friedel-Crafts cyclization, a novel photodecarbonylation reaction to form highly substituted benzofurans was discovered.;To complete the synthesis, a benzofluorene resulting from intramolecular Friedel-Crafts acylation of a Boc-protected carboxylic acid was further functionalized. Bis-silylation, mesylhydrazone formation, and an oxidation with spontaneous desulfination formed the diazo and resulting bis-silyl-protected FL-120B'. Desilylation gave FL-120B' and provided the first total synthesis of an epoxykinamycin. Furthermore, studies towards the synthesis of the lomaiviticins have been initiated and involve the synthesis of the requisite cyclohexene moiety. |
