Part 1. Exploration of Braverman Diradical Cyclizations For Angucyclinone Synthesis Part 2. Efforts Toward The Synthesis of Lomaiviticinone A
Open Access
- Author:
- Selfridge, Brandon Robert
- Graduate Program:
- Chemistry
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- August 31, 2012
- Committee Members:
- Ken S Feldman, Dissertation Advisor/Co-Advisor
Raymond Lee Funk, Committee Member
Steven M Weinreb, Committee Member
Bernhard Luscher, Special Member - Keywords:
- organic
synthesis
diradical
cyclizations
angucyclinone
lomaiviticinone A
lomaiviticins
double Ireland-Claisen - Abstract:
- Radical cyclization/addition reactions offer an efficient means to form rings within sterically congested systems. As a subset of radical-mediated closures, singlet diradical cyclizations have not been fully exploited for their potential in organic synthesis. The first part of this thesis focuses on the extension of Braverman diradical cyclizations of bis alkynyl sulfone substrates to the construction of the angucyclinone family of natural products, many of which display strong antibiotic properties. This diradical cyclization produced thiophene dioxide intermediates, which underwent formal [1,7]-hydride shifts to the more thermodynamically stable naphthalene derivatives in preference to the desired intramolecular Diels-Alder reaction with a tethered alkyne. Lomaiviticins A and B have caught the attention of the synthesis community since their isolation in 2001 due to their interesting structural features coupled with promising anticancer activity. The second part of this thesis focuses on our efforts toward the construction of the core bicyclic structure of the lomaiviticins via several independent routes. Our approaches center around two-directional synthesis in which the key C-C linkage of the dimeric structure is formed early. The three independent routes covered in this thesis are categorized as follows: 1) stereoselective bis aldol reaction, 2) stereoselective Diels-Alder reaction between 1,3-butadiene and chirally substituted enediones, 3) double Ireland-Claisen reaction of PMB glycolates containing (Z)-alkenes, which is an unprecedented transformation. The lomaiviticinone A core was successfully synthesized enantioselectively in 11 steps from a known chiral propargylic alcohol utilizing the double Ireland-Claisen reaction route.