Design and Synthesis of Enzyme Activated Irreversible Inactivators for Proteases. Suicide Inactivation of Chymotrypsin

Strategies directed toward the synthesis of halo-enol lactones have been investigated. The catalytic mercury induced lactonization of acetylenic acids has been studied, and shown to proceed via a mercuronium intermediate, to give enol lactones in good yield. This methodology was adapted to afford halo-enol lactones in modest yields, and a direct halolactonization method which gave the desired halo-enol lactones in very high yields was developed. Several other routes, such as Baeyer-Villiger oxidation of (beta)-halocycloenones and dehydration of (alpha)-haloketone acids were also developed for the synthesis of halo-enol lactones. Halo-enamine lactams were synthesized via a Schmidt reaction on (beta)-halocycloenones, and adaptation of the mercury methodology to synthesis of these compounds was also briefly explored. Initial synthetic efforts directed toward the synthesis of extended and more complex analogs also have been discussed.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Krafft, Grant Arthur

• Chemistry, Organic

Language dc:language

eng

Identifier

(UMI)AAI8108568

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/67243