Some aspects of novel prostanoid acid synthesis

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.