Aspects of natural product chemistry: Biosynthesis, structure elucidation and HSCCC/MBI/FABMS

The structure and biosynthesis of cremeomycin, a novel cytotoxic antibiotic from Streptomyces cremeus NRRL 3241, were established. Cremeomycin was found to be 3-diazo-4-methoxycyclohexa-4,6-dien-2-one carboxylic acid by X-ray crystallography. Through the intermediacy of 4-methoxysalicylic acid, cremeomycin was shown to be biosynthesized by a $\rm C\sb2+C\sb2+C\sb3$ pathway in contrast to 3-amino-5-hydroxybenzoic acid and 3-aminobenzoic acid, which are made by variants of the shikimic acid pathway. Incorporation of (1-$\sp{13}$C) - scD-glucose, (6-$\sp{13}$C) - scD-glucose, (U-$\sp{13}$C$\sb6\rbrack$- scD-glucose, (1,2-$\rm\sp{13}C\sb2$) -acetate and (2-$\sp{13}$C) -acetate revealed that the C$\sb3$ piece was labeled by glucose most likely through glycolysis. The C$\sb2$ portions were found to be constructed of acetate and assembled in a tail-tail fashion as from the citric acid cycle. Two putative intermediates, (3,5-$\rm\sp2H\sb2$) -2,4-dihydroxybenzoic acid and (5-$\sp2$H) -3-amino-4-hydroxybenzoic acid, were synthesized, but were not incorporated.

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

• McGuire, James Norton

Contributors dc:contributor

• Rinehart, Kenneth L., Jr.

• Chemistry, Analytical
• Chemistry, Organic
• Chemistry, Pharmaceutical

Statement dc:rights

• Copyright 1996 McGuire, James Norton

Language dc:language

eng

Identifier

9780591088755
AAI9702605
(UMI)AAI9702605

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/20994