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

J Org Chem. 2015 Feb 6;80(3):1601-9. doi: 10.1021/jo502538b. Epub 2015 Jan 26.

Abstract

In this paper we describe a novel general synthetic approach to B1- and L1-type phytoprostanes, which are formed in vivo from free-radical-catalyzed nonenzymatic peroxidation of α-linolenic acid (1). The synthesis of phytoprostanes (RS)-9-L1-PhytoP (5), (R)-9-L1-PhytoP (5a), (RS)-16-B1-PhytoP (6), and (RS)-16-L1-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 α and β, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxylic Acids / chemistry*
  • Catalysis
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / chemistry*
  • Free Radicals / chemistry*
  • Furans / chemical synthesis*
  • Furans / chemistry*
  • Lipase / chemistry*
  • Prostaglandins / chemical synthesis*
  • Prostaglandins / chemistry*
  • Stereoisomerism

Substances

  • Carboxylic Acids
  • Fatty Acids, Unsaturated
  • Free Radicals
  • Furans
  • Prostaglandins
  • phytoprostane B1 type I
  • Lipase