Toward the elucidation of the metabolism of 15-E(2)-isoprostane: the total synthesis of the methyl ester of a potential central metabolite.
An 11-step total synthesis of the methyl ester of a potential metabolite of the autoxidatively formed natural product 15-E(2)-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 E(2)-IsoP metabolites are highly epimerization-sensitive and that they may thus also contribute to PGE(2)-action and metabolism.
Jahn
Ullrich
U
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo namesti 2, 16610 Prague 6, Czech Republic. jahn@uochb.cas.cz
Dinca
Emanuela
E
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry*; D003500:Cyclization; D028421:Isoprostanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000085:Acetates; D028421:Isoprostanes; C007650:ethyl acetate