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Title:Studies on secondary metabolites produced by actinomycetes and cyanobacteria
Author(s):Choi, Byoung Wook
Doctoral Committee Chair(s):Rinehart, Kenneth L., Jr.
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Health Sciences, Toxicology
Chemistry, Biochemistry
Chemistry, Organic
Abstract:Biosynthetic studies compounds showed that the Adda unit of nodularin was derived from C-2, C-3 and the phenyl ring of scL-phenylalanine as well as acetate and methionine. A separate feeding experiment with (2-$\sp{13}$C) pyruvate suggested that the methylaspartate (MeAsp) unit could be derived from pyruvate and acetate.
An acyclic nodularin, N-842, was isolated from the cultured Nodularia spumigena and its structure was assigned as Adda- scD-Glu-Mdhb- scD-MeAsp- scL-Arg-OH. Isolation of nodularin and N-842 from a continuously cultured batch suggested that N-842 is a biogenetic precursor to nodularin. Based on these findings, biogenetic pathways of nodularin and the structurally related compound, microcystin-LR, are proposed.
Dihydro derivatives of nodularin and microcystin-LR were prepared by sodium borohydride reduction of the dehydroamino acid residues. The stereochemistry of each reduced amino acid was obtained by acid hydrolysis of dihydro derivatives followed by GC analysis of their trifluoroacetyl methyl ester derivatives. Deuterated derivatives were prepared in an analogous manner using sodium borodeuteride.
Analysis of FABMS/MS spectra of the linear peptides, which were obtained from ozonolysis followed by sodium borohydride reduction and acid treatment of microcystins, allowed elucidation of the sequence of the microcystins.
The fate of the dihydromicrocystin-LR's in pigs was studied by isolating the radioactive metabolites from tritiated dihydromicrocystin-LR injected pigs. Greater than 90% of the radioactive material from the liver proved to be the parent toxins. The remaining radioactivity was attributed to several unidentified metabolites.
Unlabeled 4,5,6-tri-O-benzylvalienamine was synthesized from methyl $\alpha$- scD-glucopyranoside in 12 steps in an overall yield of 5%. Similarly, (7-$\sp{14}$C) -4,5,6-tri-O-benzylvalienamine was prepared from the reaction of 2 scL-(2,4/3)-2,3,4-tribenzyloxy-cyclohex-5-enone with (methyl-$\sp{14}$C) methyltriphenylphosphonium bromide in 5 steps for an overall radiochemical yield of 9%.
The $\sp1$H and $\sp{13}$C NMR spectra of fortimicin B were assigned by use of homonuclear correlation spectroscopy, heteronuclear correlation spectroscopy and the Attached Proton Test. Feeding experiments with $\sp{14}$C-labeled plausible precursors showed that scD-glucose was not incorporated into fortimicins and scD-maltose was incorporated.
Issue Date:1992
Rights Information:Copyright 1992 Choi, Byoung Wook
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9236426
OCLC Identifier:(UMI)AAI9236426

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