Key Intermediates for introducing a bulky bicyclo[3.3.0]heptane skeleton in the w-side chain to reduce the enzyme inactivation of prostaglandins

Abstract

In vivo, the prostaglandins (PGs) are inactivated by enzyme oxidation of the 15-α-OH group to 15-keto group. 15-, 16-Substituents, 16-Aryloxy and others diminished this inactivation [1]. We planed to diminish inactivation by introducing bulky bicyclo[3.3.0]octane or bicyclo[3.3.0]oct-6-ene substituents linked to the C-15 carbon atom, but also to introduce this fragment found in nature and in compounds with anticancer activity. ω-Side chain of PGs are introduced by an E-HEW-stereoselective olefination of an aldehyde with a β-ketophosphonate (Corey procedure). The β-ketophosphonates were synthesized from bicyclo[3.3.0]oct(a)ene acids by a two or three step sequence in good yields and used for obtaining a new PG.