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Synthesis of substrates and analogs for the enzymes of vitamin B₁₂ biosynthesis
dc.contributor.advisor | Scott, A. Ian | |
dc.creator | Danso-Danquah, Richmond Edward | |
dc.date.accessioned | 2020-09-02T20:11:48Z | |
dc.date.available | 2020-09-02T20:11:48Z | |
dc.date.issued | 1990 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/DISSERTATIONS-1174800 | |
dc.description | Typescript (photocopy). | en |
dc.description.abstract | The synthesis of some of the postulated intermediates in the pathway of vitamin B12 biosynthesis, precorrins-4A, -4B and -5, were initiated. The different ring precursors necessary for the precorrins were prepared as racemic mixtures apart from ring C precursors of precorrin-5 and -4A and -4B, which were obtained optically pure from (+)-camphor and pyrrole respectively. A new method was developed to synthesize a meso-substituted symmetrical dipyrromethane which served as a key intermediate in the synthesis of 20-methyluroporphyrin III and its derivative, 12-decarboxylated-20-methyl-uroporphyrin III. Unlike the 20-H analogs, these uro'gens were found to be unstable. From initial experiments, incubation of 20-methyl-uro'gen III with methylase-1 (M-1) enzyme resulted in the production of a chlorins and isobacteriochlorins as detected by high pressure liquid chromatography coupled with UV, while the action of M-1 on 12- decarboxylated-20-methyl uro'gen III did not show production of any methylated porphyrin. A number of substrate analogs for two enzymes, PBG deaminase and ALA dehydratase, involved in the vitamin B12 biosynthesis were synthesized. Three novel oxa analogs of PBG : the oxa analog, 2-aminomethyl-4-(2-carboxyethyl)-3- carboxymethyl furan, the oxa analog of iso PBG, 2-aminomethyl-3-(2-carboxyethyl)- 4-carboxymethyl furan and its hydroxy derivative, 2-hydroxymethyl-3-(2- carboxyethyl)-4-carboxymethyl furan were prepared. These products have been tested with PBG deaminase and found not to be substrates of the enzyme. In parallel with this study, 5-hydroxylevulinic acid (the hydroxy analog of ALA) was synthesized and found not to be a substrate of ALA dehydratase when tested with the enzyme. Another novel analog of PBG, 2-(hydroxy-1-propene)-4-(2-carboxyethyl)- 3-carboxymethyl pyrrole, was synthesized as the Z isomer. The intermediate, 2- (3-phthalimido-1-propene)-4-(2-methoxycarbonylethyl)-3-methoxycarbonylmethyl pyrrole, was found to be unstable and in the presence of traces of water gave 2 - (hydroxy-1-propene)-4-(2-methoxycarbonylethyl)-3-methoxycarbonylm ethyl pyrrole. Interestingly, the action of PBG deaminase on this PBG analog showed the formation of an ES1 enzyme-substrate complex. | en |
dc.format.extent | x, 125 leaves | en |
dc.format.medium | electronic | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.rights | This thesis was part of a retrospective digitization project authorized by the Texas A&M University Libraries. Copyright remains vested with the author(s). It is the user's responsibility to secure permission from the copyright holder(s) for re-use of the work beyond the provision of Fair Use. | en |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Major chemistry | en |
dc.subject.classification | 1990 Dissertation D191 | |
dc.subject.lcsh | Vitamin B12 | en |
dc.subject.lcsh | Biosynthesis | en |
dc.subject.lcsh | Heterocyclic chemistry | en |
dc.subject.lcsh | Porphyrins | en |
dc.title | Synthesis of substrates and analogs for the enzymes of vitamin B₁₂ biosynthesis | en |
dc.type | Thesis | en |
thesis.degree.grantor | Texas A&M University | en |
thesis.degree.name | Doctor of Philosophy | en |
thesis.degree.name | Ph. D | en |
dc.contributor.committeeMember | Barton, Derek H. R. | |
dc.contributor.committeeMember | Gunn, J. Martyn | |
dc.contributor.committeeMember | Kelly, Jeffery W. | |
dc.type.genre | dissertations | en |
dc.type.material | text | en |
dc.format.digitalOrigin | reformatted digital | en |
dc.publisher.digital | Texas A&M University. Libraries | |
dc.identifier.oclc | 24091017 |
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