General Strategy for the Synthesis of B1 and L1 Prostanoids: Synthesis of Phytoprostanes (RS)-9-L1-PhytoP, (R)-9-L1-PhytoP, (RS)-16-B1-PhytoP, and (RS)-16-L1-PhytoP

In this paper we describe a novel general synthetic approach to B-1- and L1-type phytoprostanes, which are formed in vivo from free-radical-catalyzed nonenzymatic peroxidation of a-linolenic acid (1). The synthesis of phytoprostanes (RS)-9-L-1-PhytoP (5), (R)-9-L-1-PhytoP (5a), (RS)-16-B1-PhytoP (6), and (RS)-16-L-1-PhytoP (7) exemplifies this strategy. The common starting compound 8 has been proved to be synthetically equivalent to a cyclopent-2-en-1-one synthon having opposite donor and acceptor properties at carbons alpha and beta, respectively. Key steps include the chemoselective lithiation of a 1-iodo-2-bromoolefin, the introduction of the side chains by transition-metal catalysis following Heck- or Suzuki-type protocols, the construction of an enone moiety by a mild Au(I)-catalyzed Meyer Schuster rearrangement, and a lipase-mediated hydrolysis of methyl esters to deliver the phytoprostanes as free carboxylic acids.