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Studies on the biosynthesis of indole alkaloids

University of British Columbia

In Part A of this thesis a study of the later stages of the biosynthesis of indole alkaloids is described. This study is divided into three sections, the first centres on a versatile synthesis of secodine (67) through which certain derivatives can be prepared. Ethyl indole-2-carboAylate was reduced and homologated to methyl indole-2-acetate (89) which was converted to β-[3-(2-carbomethoxymethyl)- indolyl]-ethanol (90). Treatment of the alcohol (90) with p-toluene- sulphonylchloride in 3-ethylpyridine followed by reduction gave N-{β-[3-(2-carbonethoxymethyl)-indolyl]-ethyl}-3'-ethy1-3'-piperideine (81) and β-[3- (2-carbomethoxymethyl)-indolyl]-ethylchloride (85). A pathway is proposed for the formation of the latter compound. The ester (81) was converted to secodine (67) by a known sequence. Reduction of 3-acetylpyridine (106) with sodium borotritide produced an alcohol (107) -which was acetylated and hydrogenated to yield [1- ³H]-l-(3'-pyridyl)-ethane. Condensation of this molecule with the alcohol (90) gave the ester (81) which was converted to [19-³H]-secodine. The biological evaluation of secodine (67) as a potential precursor for the indole alkaloids, catharanthine (16) and vincamine (7) is described in Sections B and C. Using various labelled forms of secodine (67), double isotope studies with the plant species Vinca minor and Vinca rosea established the specific'incorporation of the molecule into catharanthine (16) and vincamine (7). Degradation of these alkaloids confirmed that the entire secodine molecule (67) was incorporated intact. Part B describes a preliminary investigation into the isolation of enzymes concerned with the biosynthesis of eleagnine (5). The isolation of this molecule from Eleagnus angustifolia and synthesis of possible labelled precursors is outlined in Section A. A study of the nuclear magnetic resonance spectrum of N[sub b]-acetyleleagnine is also described. Section B reveals the initial procedures used to isolate protein extracts and their assay.

Text

2011-03-03

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http://hdl.handle.net/2429/31947

Chemistry

University of British Columbia

Graduate