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Syntheses of linear tetrapyrroles as potential inhibitors for uroporphyrinogen III synthase
dc.contributor.advisor | Scott, A. Ian | |
dc.creator | Xue, Tianhan | |
dc.date.accessioned | 2020-09-02T20:12:19Z | |
dc.date.available | 2020-09-02T20:12:19Z | |
dc.date.issued | 1992 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/DISSERTATIONS-1293023 | |
dc.description | Typescript (photocopy). | en |
dc.description.abstract | Living systems depend on a variety of metal complexes of tetrapyrrolic macrocycles to carry out many biologically important functions. Among these pigments of life are heme, chlorophyll and vitamin B[12]- All these substances are biosynthetically derived from the same macrocyclic precursor, uroporphyrinogen III. In Nature, the latter is constructed from a linear tetrapyrrole, hydroxymethylbilane, by an enzyme named uroporphyrinogen III synthase or cosynthetase. In order to elucidate the mechanism of action of cosynthetase, a variety of linear tetrapyrrolic compounds have been synthesized as potential inhibitors for the enzyme. Four new hydroxymethylbilane derivatives (D ring N-methyl hydroxymethylbilane 30, acetyl bilane 62, trifluoroacetyl bilane 64, and 19-carbobenzoxy hydroxymethylbilane methyl ester 69) have been synthesized, together with the known formylbilane 26. These syntheses employed the established "2 + 2" approach, and the key step was acid-catalyzed condensation of two dipyrromethane precursors bearing the desired array of substituents. Aminomethylbilane 5 has been prepared through the tripyrrene / a, c-biladiene route. The benzyl ester in the tripyrrene precursor was cleaved by vigorous acid treatment, a modification of a recently reported procedure. Borohydride reduction of biladiene-a,c salt led to aminomethylbilane lactam methyl ester whose lactam ring and side-chain esters were saponified to afford the aminomethylbilane. An alternative approach to aminomethylbilanes has been developed. It is based on catalytic hydrogenation of a bilene-a derivative in which the terminal α position was unprotected. The required bilene-a was constructed by acid-catalyzed condensation of an appropriate tripyrrane-α-carboxylic acid with an α-formyl-pyrrole. The new route is demonstrated in the syntheses of amino-methylbilane and 18-butyrate aminomethylbilane 78... | en |
dc.format.extent | viii, 109 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 | 1992 Dissertation X8 | |
dc.subject.lcsh | Biosynthesis | en |
dc.subject.lcsh | Tetrapyrroles | en |
dc.subject.lcsh | Synthesis | en |
dc.subject.lcsh | Enzyme inhibitors | en |
dc.title | Syntheses of linear tetrapyrroles as potential inhibitors for uroporphyrinogen III synthase | 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 | Gunn, John M. | |
dc.contributor.committeeMember | Harding, Kenn E. | |
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 | 27881375 |
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