Studies towards the diazobenzofluorene natural products: total synthesis of the epoxykinamycin FL-120B'
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Abstract
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 Friedei-Crafts acylation provided the tetracyclic carbon framework of
FL-120B'. The successful outcome of the Friedei-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 FriedelCrafts acylation of a Hoc-protected carboxylic acid was further functionalized. Bissilylation, 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.
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Thesis (Ph.D.)--Boston University
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PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.