Synthetic studies towards pyrrolizidine and indolizidine alkaloids.

MITCHELL, Douglas. (1992). Synthetic studies towards pyrrolizidine and indolizidine alkaloids. Doctoral, Sheffield Hallam University (United Kingdom)..

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Abstract

This project was concerned with the synthesis of the pyrrolizidine alkaloids supinidine, trachelanthamidine and isoretronecanol and also synthetic studies towards the indolizidine alkaloid 251D. In all cases, the synthesis began from a cheap, readily-available, simple amino acid, in this case glutamic acid, and proceeded to a suitable monocyclic intermediate which could then undergo an intramolecular Horner-Wittig cyclisation reaction to form the required bicyclic core structure. Subsequent modification reactions then led in the pyrrolizidine series to penultimate precursors of the target alkaloids supinidine, trachelanthamidine and isoretronecanol, and in the indolizidine series to a bicyclic intermediate in the synthesis towards the toxin 251D. The intramolecular Horner-Wittig cyclisation reaction was found to proceed with retention of chirality, thus leading to the enantiospecific synthesis of the pyrrolizidine alkaloids. The use of alternative monocyclic intermediates in the intramolecular Horner-Wittig cyclisation reaction, thus leading to other pyrrolizidine alkaloids is also discussed.One of the major problems encountered in this project was the solubility of the unprotected monocyclic amide intermediates, and this was overcome by the use of N-benzyl and N- carbobenzyloxy protecting groups; in the indolizidine synthesis where the unprotected monocyclic amides were necessary, the reaction work-up for these intermediates usually required continuous solvent extraction. Another major problem was the instability of the bicyclic amide intermediates and some of the monocyclic intermediates,As well as covering a comprehensive background of each class of alkaloid, this report also contains an in-depth discussion of the key intramolecular Horner-Wittig cyclisation reaction and suggestions for its use in the possible synthesis of other classes of alkaloids.

Item Type: Thesis (Doctoral)
Additional Information: Thesis (Ph.D.)--Sheffield Hallam University (United Kingdom), 1992.
Research Institute, Centre or Group: Sheffield Hallam Doctoral Theses
Depositing User: EPrints Services
Date Deposited: 10 Apr 2018 17:21
Last Modified: 23 May 2018 12:11
URI: http://shura.shu.ac.uk/id/eprint/20067

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