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Title:Aspects of natural product chemistry: Biosynthesis, structure elucidation and HSCCC/MBI/FABMS
Author(s):McGuire, James Norton
Doctoral Committee Chair(s):Rinehart, Kenneth L., Jr.
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Analytical
Chemistry, Organic
Chemistry, Pharmaceutical
Abstract: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.
A system for on-line detection in high-speed countercurrent chromatography using fast atom bombardment mass spectrometry through a moving belt interface (HSCCC/MBI/FABMS) was assembled. Analytes that are normally difficult to see by optical methods were detected by the mass spectrometer and identified using the resulting structural information. The MBI displayed advantages over thermospray and frit FAB (also CF-FAB) with respect to back-pressure and flow-rate compatibility, respectively. Furthermore, the MBI did not require the addition of a FAB matrix, which can sometimes adversely affect chromatographic separations.
Issue Date:1996
Rights Information:Copyright 1996 McGuire, James Norton
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9702605
OCLC Identifier:(UMI)AAI9702605

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