PART I. STUDIES TOWARD THE SYNTHESIS OF DIAZONAMIDE A. PART
II. A PROPOSAL FOR THE MECHANISM-OF-ACTION OF
DIAZOPARAQUINONE NATURAL PRODUCTS AND STUDIES TOWARD THE
SYNTHESIS OF KINMYCIN F.
Open Access
Author:
Eastman, Kyle Joseph
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
August 03, 2006
Committee Members:
Ken S Feldman, Committee Chair/Co-Chair Raymond Lee Funk, Committee Member Christopher Falzone, Committee Member Martin Bollinger, Committee Member
The synthesis of an indole salicylate with the required axial chirality for
diazonamide A are reported. Atropselectivity in this biaryl system are secured by a
proximal sp3 stereogenic center.
A model system for a novel photochemically induced cyclization to of a
benzotriazole alkene to give a C(2) disubstituted indolenine is developed. Extension of
this model system to an approach toward the synthesis of diazonamide A is described.
The putative reductive activation chemistry of the diazoparaquinone
natural products was modeled with Bu3SnH and prekinamycin dimethyl ether along with
prekinamycin itself. Reactions in a various combinations of aromatic solvents, with and
without the nucleophile benzylmercaptan present, led to isolation of both radical trapping
arene adducts and nucleophile capture benzyl thioether products. Based on these product
distribution studies, the intermediacy of first, a cyclopentenyl radical, and subsequently,
an orthoquinonemethide electrophile, is proposed.
Lastly, the preparation of a Nazarov cyclization precursor and attempted
cyclizations aimed at securing the benzo[b]fluorenone core of kinamycin F is detailed.
