Halo Enol Lactones as Enzyme-Activated Irreversible Inhibitors of Alpha-Chymotrypsin: I. The Effect of Lactone Substitution Pattern. Ii. Alpha - Amino-Functionalized Lactones

Halo enol lactones with a phenyl group situated (beta) or (gamma) to the lactone carbonyl group were prepared to compare their effectiveness as enzyme-activated irreversible (suicide) inhibitors for (alpha)-chymotrypsin with the activities of the corresponding (alpha)-substituted lactones. The 4-phenyl-5(E)-(iodomethylidene) tetrahydro-2-furanone, the 4-phenyl-5(E)-(iodomethylidene)dihydro-2-furanone, the 4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone and the 5-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone were prepared using a halolactonization reaction to convert the appropriate phenyl-substituted acetylenic acid into the corresponding lactone. The 4-phenyl-tetrahydrofuranone and the 5-phenyl-tetrahydropyranone only proved to be competitive inhibitors, and the 4-phenyl-dihydrofuranone appeared to be neither an irreversible inhibitor nor a competitive inhibitor. However, the 4-phenyl-tetrahydropyranone temporarily inactivated (alpha)-chymotrypsin presumably by the formation of a stable acyl-enzyme complex as suggested by experimental data.

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

• Sofia, Michael Joseph

• Chemistry, Organic

Identifier

(UMI)AAI8502303

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/70285