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Studies on the biosynthesis of podophyllotoxin:synthesis of labelled yatein and matairesinol, two potential precursors of podophyllotoxin

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dc.contributor.authorNeidigh, Kurt Alanen
dc.contributor.departmentChemistryen
dc.date.accessioned2014-03-14T21:46:08Zen
dc.date.adate2009-09-19en
dc.date.available2014-03-14T21:46:08Zen
dc.date.issued1992en
dc.date.rdate2009-09-19en
dc.date.sdate2009-09-19en
dc.description.abstractPodophyllotoxin, a naturally occurring lignan isolated from several species of Podophyllum, is used as a precursor to the clinical chemotherapeutic agents teniposide and etoposide. The biosynthesis of podophyllotoxin is not fully understood, but its optical activity, like that of most lignans, is suggestive of enzyme-mediated processes. It has been proposed that the formation of podophyllotoxin begins with stereo-controlled coupling of a hydroxy cinnamyl alcohol derivative and a substituted hydroxy Cinnamic acid, although no "coupling" enzyme has been isolated to date. Further biosynthetic modifications of the coupled compound could lead to matairesinol and/or yatein, which have been proposed as potential biological precursors of podophyllotoxin. Although no firm evidence has been obtained to date, conversion of matairesinol to yatein has been postulated. This conversion would, however, involve biosynthetic steps which, though common for hydroxycinnamates, are unprecedented at the dimeric level. Conversion of yatein to podophyllotoxin has been demonstrated, with the conversion involving a stereo-controlled cyclization and subsequent stereospecific hydroxylation. In order to investigate the biosynthesis of podophyllotoxin, leading from the postulated precursors matairesinol and yatein, a series of stereospecific deuterium-labelled matairesinol and yatein derivatives was proposed and the synthetic methodology for each compound developed. The methodology used to obtain deuterium-labelled compounds can be extended to generating tritium-labelled compounds as well. With sufficient quantities of a number of the deuterium-labelled compounds, feeding studies can now be carried out in Podophyllum plants. Isolation and analysis of podophyllotoxin, from plants fed with labelled yatein, will allow determination of the stereochemical nature of yatein cyclization. Isolation and analysis of yatein, from plants fed with labelled matairesinol, will indicate whether matairesinol is indeed a precursor to yatein (and, hence, podophyllotoxin). The information obtained from the synthesis and incorporation of such labelled compounds should then provide a clearer understanding of some interesting but, as yet, unestablished biotransformations.en
dc.description.degreeMaster of Scienceen
dc.format.extentviii, 134 leavesen
dc.format.mediumBTDen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheretd-09192009-040255en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-09192009-040255/en
dc.identifier.urihttp://hdl.handle.net/10919/44847en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartLD5655.V855_1992.N442.pdfen
dc.relation.isformatofOCLC# 26000770en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V855 1992.N442en
dc.subject.lcshAntineoplastic agents -- Synthesisen
dc.subject.lcshPodophyllotoxin -- Synthesisen
dc.titleStudies on the biosynthesis of podophyllotoxin:synthesis of labelled yatein and matairesinol, two potential precursors of podophyllotoxinen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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