posted on 2018-08-10, 11:03authored bySteve M.F. Lai
The synthesis of prostaglandins is reviewed and the strategy of
the more important and interesting approaches is discussed.
The synthesis of a model prostanoid via a novel three-stage
approach is described. This involved a Claisen-type condensation of
diethyl azelate to methyl nonyl ketone to form a C20 1,3-diketo-ester.
Dimethylation of the active methylene at the C-10 position of the 1,3-diketo-ester, followed by cyclisation across the C-8, C-12 positions,
afforded the novel ethyl 10,10-dimethyl prost-8(12)-en-9,11-dionoate.
This synthetic approach was subsequently applied to the preparation of
the novel ethyl 10,10-dimethyl prost-8(12), 15-dien-9,11-dionoate and
ethyl 10,10-dimethyl-15-benzyloxy-prost-8(12)-en-9,11-dionoate.
Other methods of effecting the C-8, C-12 cyclisation of 8,12-dibromo-10,10-dimethyl-eicos-9,11-dionoic esters were investigated. Finally, the
cyclisation of simpler 1,3-diketone models, 3,7-dibromo-5,5-dimethyl-nona-4,6-dione and 5,9-dibromo-7,7-dimethyl-trideca-6,8-dione was investigated.
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/
Publication date
1978
Notes
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy at Loughborough University.