New β-ketophosphonates for the synthesis of prostaglandin analogues. 2 Phosphonates with bicyclo[3.3.0]octene and bicyclo[3.3.0]octane scaffolds linked to the β-keto group

Abstract

β-Ketophosphonates, with the keto group linked to a bicyclo[3.3.0]oct(a)ene fragment, were synthesized starting from two diacids. These diacids were first transformed into internal anhydrides and one into a diester. The anhydrides and the diester were reacted with the lithium salt of dimethyl methanephosphonate to give two carboxy β-ketophosphonates, an ester β-ketophosphonate and a bis β-ketophosphonate in good yield. The ester β-ketophosphonate, obtained by two routes was used in the E-HEW selective olefination of a prostaglandin aldehyde with an α-side chain to give the 15-keto prostaglandin analogue in good yield. The compounds were characterized by elemental analysis, IR and high resolution ¹H- and ¹³C-NMR spectroscopies.