Progress towards the enantioselective total synthesis of trichodermamide B

Trichodermamide B is an unusual modified dipeptide natural product, with very promising anticancer activities. While the biosynthesis of this molecule is unknown, it is proposed herein that it is formed in vivo through direct oxidation of phenylalanine to the arene oxide or arene dioxide intermediate, which is then opened via nucleophilic attack of an oxime. To probe the feasibility of this biosynthetic hypothesis, a series of bioinspired approaches to trichodermamide B have been investigated, proceeding through arene oxide equivalents. Progress towards the concise and practical total synthesis of this molecule are described herein. Notable transformations explored include the mild installation of an oxime with hydrogen atom transfer, and microbial arene oxidation to generate decagram amounts of enantiopure, value-added starting materials. This strategy has enabled rapid access to large quantities of advanced intermediates, and once complete, should afford the natural product as a single enantiomer in far fewer steps than previously reported.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2017

Author dc:creator

• Levinn, Carolyn M

Contributors dc:contributor

• Sarlah, David

• Trichodermamide B
• Total synthesis
• Microbial arene oxidation
• Arenophile
• Arene oxide

Statement dc:rights

• Copyright 2017 Carolyn Levinn

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/97625

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/97625