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

Abstract

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.

Highly Functionalized and Potent Antiviral Cyclopentane Derivatives Formed by a Tandem Process Consisting of Organometallic, Transition‐Metal‐Catalyzed, and Radical Reaction Steps

“…Isomerization as a potential link to join nucleophilic addition with enolate chemistry. With optimal conditions for the isomerization of alkoxides to enolates established, the tandem sequence was elaborated; it consists of: 1) nucleophilic addition of several aryllithium reagents 1 to a,b-unsaturated aldehydes 2, 2) isomerization catalyzed by Cat-1, 3) Michael addition of the resulting enolates to acceptors 6, 4) SET oxidation to the corresponding radicals by selective SET oxidant ferrocenium hexafluorophosphate 7, [16] 5) radical cyclizations to construct a fivemembered ring, and finally 6) CÀO bond formation by reaction with persistent radical TEMPO 8 [17] (Scheme 3). The substrate scope is broad and only two, often partly separable anti and syn diastereomers of cyclic oxygenated products 9 a-m, both having exclusive trans stereochemistry at the cyclopentane ring, were isolated.…”

General and Efficient α‐Oxygenation of Carbonyl Compounds by TEMPO Induced by Single‐Electron‐Transfer Oxidation of Their Enolates

“…Recently, an oxidative deprotection of N ‐alkoxy‐2,2,6,6‐tetramethylpiperidines leading to aldehydes or ketones was reported 37. Although this method is indeed generally applicable to alkyl or allyl derivatives,12d,12f it gave a complex mixture when applied to 15c or 15d .…”

Rapid and Structurally Diverse Synthesis of Multi‐Substituted β‐Keto Amide Derivatives Based on a Dioxinone Scaffold

“…Many elegant syntheses, including total syntheses of natural products, have been reported using this feature of dioxinones. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] The dioxinones are also attractive as molecular scaffolds for assembling building blocks, because they provide multiple reaction centres for various chemical modifications. [17,23] In this paper, we report the rapid synthesis of structurally diverse multi-substituted β-keto amide derivatives using a sequential diversification approach based on a simple and readily available dioxinone scaffold 5.…”