Elaboration of the ω-chain of 11-deoxyprostanoid derivatives through isoxazole intermediates.

A new versatile approach to the synthesis of ll-deoxyprostanoic acid derivatives, which entails the use of 3,&diaubatituted iaoxazoles as source of the eight carbon atoms of the wchain, is degcribed. The key step involves the formation of the C(13)<(14) bond through a [3 + 21 cycloaddition of the nitrile oxides generated from 3~-(nitromethyl)-2a-substituted-cyclopentanoncey cloethylene ketals (10,22,31) to l-heptyne to give the corresponding isoxazoles (12,24,32), the wide chain of 24 and 32 being completed through Wittig condensation to give 26 and 36. Reductive ring opening of the heterocycle under Birch-like conditions gave rise to the &amino ketones 14,27, and 37, which underwent a silica gel assisted loss of ammonia to produce the a,b-unsaturated ketones 15,28, and 38, precursors of the vinylamylcarbinol side chain of prostaglandins (PGs). The alternative reductive ring opening of the isoxazole 12 allowed us to obtain the allylically transposed enone 19, leading to a new preparation of 13-hydroxyprostanoic acid derivatives 21