Approaches to the synthesis of steroidal [alpha]-methylene lactones

A brief review of the biological properties and the synthesis of α-methylene-γ- and -δ-lactones is presented. Estrone 69 was converted to estrololactone-methyl ether 71 which was α-formylated with ethyl formate, diethylaminated, hydrogenated and underwent β-elimination to the 3-methoxy-16-methylene-17-oxa-17a-oxa-D-homo-estra-1,3,5(10)-triene 75 which was reduced to the 16-methyl lactone 77 and thiolated to the thiol-adduct 76. The estrololactone 70a was α-formylated, acetylated, diethylaminated, hydrogenated and underwent β-elimination to the 3-acetoxy-16-methylene-17-oxo-17a-oxa-D-homo-estra-1,3,5(10)-triene 99 which was hydrolysed to the 3-hydroxy-16-methylene lactone 78. The reaction of the estrololactone methyl ether 71 with triphenylphosphonium ethyl bromide gave 3-methoxy-16-isopropylidene-17-oxo-17a-oxa-D-homo-estro-1,3,5(10)-triene 100. [Continues.]