Stereoselective synthesis of a cis-1,2-dialkylcyclopentane building block and its application in isoprostane synthesis (5-ent-F2c-IsoP)

The all-cis substituted cyclopentane 3a, an analogue of the Corey lactone, has been prepared from a readily available nortricyclanone derivative by a five-step sequence in an overall yield of 34 %. This chiral building block has been applied in total syntheses of two diastereomeric isoprostanes belonging to the 5-F-2 family: ent-5-F-2c-IsoP (ent-1) and 5-epient-5-F(2)c-IsoP (ent-2). Key features of the syntheses are the introduction of the two unsaturated alkyl side chains through an E-selective Horner-Wadsworth-Emmons reaction with the base-sensitive syn-aldehyde 10, along with a Z-selective Wittig olefination. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).