Highly efficient total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and their analogues

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 alpha-chain at the gamma position. Aldol reaction of this enone with the w-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al2O3 furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Delta(12_)PGJ(2) efficiently. Similarly, 15-deoxy-Delta(12,14_)PGJ(2), 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized. (c) 2006 Elsevier Ltd. All rights reserved.