Highly efficient total synthesis of Δ 12-PGJ 2, 15-deoxy-Δ 12,14-PGJ 2, and their analogues

Abstract

Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al 2O 3 furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Δ 12-PGJ 2 efficiently. Similarly, 15-deoxy-Δ 12,14-PGJ 2, 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized.