TRIPLY CONVERGENT SYNTHESIS OF 15-(PHENOXYMETHYL) AND 4,5-ALLENYL PROSTAGLANDINS - PREPARATION OF AN INDIVIDUAL ISOMER OF ENPROSTIL

A triply convergent synthesis of the PGE2 derivatives 1, 3, 4, and 5, containing either the 15-(phenoxymethyl) or the 15-amyl omega side chain and the 5,6-didehydro or the 4,5-allenyl alpha side chain, is described. This two-pot method employs organocopper reagents of the type Li2RomegaCuCNMe to selectively introduce the omega side chain to enantiopure enone 6 followed by in situ trapping of the so-formed enolates as silyl enol ethers 22a and 22b. The kev step is the alkylation of regiochemically defined lithium enolates, generated from the corresponding silyl enol ethers 22a and 22b, with the unsaturated alpha side chain triflates 8b and 9c. The method was found to be general for propargylic and allenic alpha side chains but unsuccessful for the cis allylic and saturated a side chains found in PGE2 and PGE1, respectively.