Investigations in Enzyme Stereospecificity: I. The Stereochemistry of Cis-Double Bond Formation in Dolichol and Natural Rubber Biosynthesis. II. The Stereochemistry of Carbon-Sulfur 4ond Reduction by Methyl Coenzyme Reductase

Dolichol, a poly-cis polyprenol, is biosynthesized from isopentenyl pyrophosphate, IPP, and farnesyl pyrophosphate, FPP, as a branch from the pathway to squalene and cholesterol. Natural rubber, also a poly-cis polyprenol, is biosynthesized from Hevea latex in the same manner. The stereochemical details of the condensation of IPP with the pro-chiral center of the developing dolichol and rubber chains are important in both analysis of the spatial arrangement of the enzyme-substrate complex and in the design of inhibitors or regulators for the pathway. Tritium labeled dehydrodolichol and natural rubber were biosynthesized from both (1S)- (1-$\sp3$H$\sb1$) IPP and (E)- (4-$\sp3$H$\sb1$) IPP by Dr. Hiroshi Sagami at Tohoku University in Sendai, Japan. The configuration of the tritium label located at the newly generated allylic position in the biosynthesized rubber and dehydrodolichol chains was determined in three of the four products. Elucidation of the stereochemistry of the products was accomplished through reductive ozonolysis to 1,4-pentanediol and 2-methyl 2,5-hexanediol followed by resolution of the diol enantiomers and stereospecific degradation. The key step in both degradations was a selenoxide syn elimination to form a mixture of both E and Z alkenes.

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

• Schlicher, Martha Ann

Contributors dc:contributor

• Coates, Robert M.

• Chemistry, Organic

Identifier

(UMI)AAI8908830

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/70432