A synthesis of prostaglandins.

CAMERON, Andrew G. (1983). A synthesis of prostaglandins. Doctoral, Sheffield Hallam University (United Kingdom)..

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Abstract

As an introduction current general approaches to the chemical synthesis of prostaglandins are reviewed latterly concentrating upon the synthesis of the 'D' series. A total synthesis of the prostaglandin, PGD[1] methyl ester and epimers is presented this being developed using the following synthetic pathway. Alkylation of alkyl dialkoxyacetates proved successful, results being in good agreement with those published en route by Huet. The resulting intermediates (including one bearing an alpha-prostanoid side chain) were converted in high yield over two steps to the desired alpha-diketodithianes thus improving a dangerous non-flexible literature procedure. These compounds underwent a cyclization reaction with appropriate vinyl phosphonium salts (developed in our laboratories) to afford highly substituted cyclopentenones in greater than 70% yield. The appropriate prostanoid cyclopentenones were transformed over three steps in 55% yield to a 2-alkylcyclopentenone substrate which was reacted with an organocuprate reagent as a means of introducing the o-prostanoid side chain. Conjugate addition proceeded with asymmetric induction at the C-12 centre a 3.5:1 diastereomeric preference in favour of the desired stereochemistry was observed. Reduction at the C-9 centre proceeded to give the undesired beta-stereochemical outcome (this product was transformed into the C-9epimer of PGD[1]). Inversion of the stereochemistry at C-9 was achieved by an S[N]2 displacement reaction to give the 9 alpha-alcohol in 52% yield from its epimer. The resultant product was deprotected to afford PGD[1] methyl ester accompanied by its ent-15-epimer.A total synthesis of (+) dihydrojasmololone is outlined incorporating a similar synthetic strategy and some suggestions for extension of the project are proposed. Full experimental details are given.

Item Type: Thesis (Doctoral)
Additional Information: Thesis (Ph.D.)--Sheffield Hallam University (United Kingdom), 1983.
Research Institute, Centre or Group: Sheffield Hallam Doctoral Theses
Depositing User: EPrints Services
Date Deposited: 10 Apr 2018 17:18
Last Modified: 10 Apr 2018 17:18
URI: http://shura.shu.ac.uk/id/eprint/19419

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