Total syntheses of all tri-oxygenated 16-phytoprostane classes via a common precursor constructed by oxidative cyclization and alkyl–alkyl coupling reactions as the key steps. Issue 44 (2nd November 2017)

• Record Type: Journal Article
• Authors: Smrček, Jakub; Pohl, Radek; Jahn, Ullrich
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 44(2017)
• Page Start: 9408
• Page End: 9414
• Publication Date: 2017-11-02
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02505j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A parallel total synthesis of 16-F1t -, 16-E1 -phytoprostanes and a first synthesis of 16-D1t -phytoprostanes based on a common precursor are described. Abstract : A unified strategy for the total synthesis of the methyl esters of all phytoprostane (PhytoP) classes bearing two ring-oxygen atoms based on an orthogonally protected common precursor is described. Racemic 16-F1t -, 16-E1 -PhytoP and their C-16 epimers, which also occur as racemates in Nature, were successfully obtained. The first total synthesis of very sensitive 16-D1t -PhytoP succeeded, however, it quickly isomerized to more stable, but so far also unknown Δ 13 -16-D1t -PhytoP, which may serve as a more reliable biomarker for D-type PhytoP. The dioxygenated cyclopentane ring carrying the ω-chain with the oxygen functionality in the 16-position was approached by a radical oxidative cyclization mediated by ferrocenium hexafluorophosphate and TEMPO. The α-chain was introduced by a new copper-catalyzed alkyl–alkyl coupling of a 6-heptenyl Grignard reagent with a functionalized cyclopentylmethyl triflate.