Toward the Elucidation of the Metabolism of 15-E2-Isoprostane: The Total Synthesis of the Methyl Ester of a Potential Central Metabolite

0345972 - ÚOCHB 2011 RIV US eng J - Journal Article
Jahn, Ullrich - Dinca, E.
Toward the Elucidation of the Metabolism of 15-E2-Isoprostane: The Total Synthesis of the Methyl Ester of a Potential Central Metabolite.
Journal of Organic Chemistry. Roč. 75, č. 13 (2010), s. 4480-4491. ISSN 0022-3263. E-ISSN 1520-6904
Grant - others:DFG(DE) Ja896/3-1
Institutional research plan: CEZ:AV0Z40550506
Keywords : isoprostane * total synthesis * radical anion cyclization
Subject RIV: CC - Organic Chemistry
Impact factor: 4.002, year: 2010

An 11-step total synthesis of the methyl ester of a potential metabolite of the autoxidatively formed natural product 15-E2-IsoP, whose metabolism is not known, is reported. Several vinylogous Mukaiyama aldol additions were tested for the assembly of the acyclic C7-C20 precursor. A new oxidative dianion cyclization served to access the cyclopentane core. The full carbon skeleton was synthesized by an acetylide alkylation. The overall yield of the metabolite amounts to 1.4% for the most efficient route. The results demonstrate convincingly that E2-IsoP metabolites are highly epimerization-sensitive and that they may thus also contribute to PGE2-action and metabolism.
Permanent Link: http://hdl.handle.net/11104/0187123