Synthetic approaches to an indole alkaloid precursor

dc.contributor.authorElmes, Alfred Royen_US
dc.date.accessioned2024-08-13T22:12:51Z
dc.date.available2024-08-13T22:12:51Z
dc.date.copyright1973en_US
dc.date.issued1973
dc.degree.departmentDepartment of Chemistry
dc.degree.levelMaster of Science M.Sc.en
dc.description.abstractIn Part 1 of this thesis, synthetic endeavours leading to the acrylic ester [56] are presented o This compound, resembling the precursor secodine [52] is postulated as having a resemblance to the dihydropyridine or dihydropyridinium intermediates implicated as being involved in the later stages in biosynthesis of the major indole alkaloid families. A suggestion is made that the new compound [56] would be a more appropriate precursor than secodine for experimental bio-evaluation. Synthesis was specifically directed at obtaining the alcohol [86], from which the expectedly unstable acrylic ester [56] could be generated in one step under carefully controlled conditions. N-[β{3(2-Carbomethoxylmethylindolyl)}ethyl]-3-acetyl-l,4,5,6-tetrahydropyridine [70] was prepared by condensation of 3-acetylpyridine with the appropriate tryptophyl derivative, followed by reduction. All attempts to alkylate in the ester side chain of [70] using methyl formate and subsequent reduction were without success. Two basic alternative routes leading to [86] were followed. One involved prior elaboration of the ester side chain, to the alcohol [88]. The alcohol group was then protected by benzylation before attempting to introduce the ethyl bridge at C-3 of the indole nucleus, condense with 3-acetylpyridine, and catalytically reduce the pyridinium salt yielding [86]. In the other method, the alcohol group of methyl 3(S-hydroxyethyl)­indole-2-acetate was 3uitably protected, either as the tetrahydropyranyl or benzyl ether, and attempts made to alkylate in the ester side chain as with [70]. The second investigation concerns the generation of 1,4-dihydro­pyridines from the corresponding pyridinium compounds having the stabil­ising 3-acetyl function. This research is related in another direction again, to the implicated biointermediate(s). Reduction of N-[β-(3-indolyl)ethyl]-3-acetylpyridinium bromide [102] with sodium hydrosulphite, gave the rather unstable N-[β(3-indolyl)ethyl]-3-acetyl-1,4-dihydropyridine [103]. Reaction of the bromide salt [102] with potassium cyanide in alcohol gave the relatively more stable cyano adduct [104]. These dihydropyridines were stable to base, but very labile to dilute acid, undergoing transformation to a mixture of products. The nature of these products in the case of the indole substituted compounds is not known with certainty.en
dc.format.extent138 pages
dc.identifier.urihttps://hdl.handle.net/1828/17702
dc.rightsAvailable to the World Wide Weben_US
dc.titleSynthetic approaches to an indole alkaloid precursoren_US
dc.typeThesisen_US

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