The synthesis and evaluation of halo and protio enol lactone Pro-Val pseudodipeptides as potential inhibitors of human leukocyte elastase

Mechanism-based inhibitors of the serine protease α-chymotrypsin have previously been prepared from aryl-substituted halo and protio enol lactones. In this study, the enantiomerically pure disubstituted protio and halo enol lactones 11a-c and 12a-b were prepared as potential inhibitors of the serine protease human leukocyte elastase (HLE). These lactones are incorporated into a Pro-Val pseudodipeptide in order to enhance binding and specificity towards HLE. The synthesis of these compounds proceeded by the cyclization of N-protected forms of the acetylenic amino acid epimers 13a and 13b. The amino acids were obtained by amide bond hydrolysis of the bicyclic oxa lactams 19a and 19b, prepared in six steps from Boc-(L)-proline.

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

2011

Author dc:creator

• Reed, Peter E.

Contributors dc:contributor

• Katzenellenbogen, John A.

• Chemistry, Biochemistry
• Chemistry, Organic
• Chemistry, Pharmaceutical

Statement dc:rights

• Copyright 1990 Reed, Peter E.

Language dc:language

eng

Identifier

AAI9114380
(UMI)AAI9114380

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/22109