Synthesis and Biosynthesis of Pyrrolizidine Alkaloids

Devlin, James Alastair (1982) Synthesis and Biosynthesis of Pyrrolizidine Alkaloids. PhD thesis, University of Glasgow.

Abstract

This work is divided into five parts: (a) Synthesis of macrocyclic diester alkaloid analogues, (b) Synthesis of a macrocyclic diester alkaloid and elucidation of its absolute stereochemistry, (c) Structural studies, (d) Synthetic approaches to pyrrolizidine bases, and (e) Biosynthetic studies. (a) Synthesis of Macrocyclic Diester Alkaloid Analogues. Treatment of (+)-retronecine with a series of substituted glutaric anhydrides resulted in the formation of mixtures of 7- and. 9- monoesters of (+)-retronecine. Cyclisation of these mixtures by the Corey-Nicolaou method led to the formation of 13-substituted 1,2-didehydrocrotalanines. 1,2-Didehydrocrotalanine, 13,13-dimethyl, 13,13-diphenyl, (13R)- and (13S)-13-methyl, and 13,13-tetramethylene-1,2-didehydro-crotalanine were synthesised by this method. (b) Synthesis of a Macrocyclic Diester Alkaloid and Elucidation of its Absolute Stereochemistry. A mixture of the 7- and 9- monoesters of (+)-retronecine was formed from (+)-retronecine and dicrotalic anhydride. This mixture was cyclised by the Corey-Nicolaou method to yield the pyrrolizidine alkaloid dicrotaline and its C-13 epimer. The absolute configuration at C-13 of both these alkaloids was determined by correlation with mevalonolactone. (c) Structural Studies. The plant Crotalaria globifera was shown to contain two pyrrolizidine alkaloids. One was shown to be trichodesmine. The other is believed to be a new pyrrolizidine alkaloid and has been named globiferine. A structure has been proposed for this alkaloid. (d) Synthetic Approaches to Pyrrolizidine Bases. Synthetic approaches to the pyrrolizidine base crotanecine based on 1,3-dipolar cycloaddition reactions and intramolecular cyclisations on iminium ions have been investigated. (e) Biosynthetic Studies. Evidence has been obtained for the incorporation of L-isoleucine and valine into the pyrrolizidine alkaloids trichodesmine and globiferine in C. globifera.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1982
• Depositing User: Enlighten Team
• Unique ID: glathesis:1982-77179
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 09:17
• Last Modified: 14 Jan 2020 09:17
• URI: https://theses.gla.ac.uk/id/eprint/77179