Stereocontrolled Access to Isoprostanes via a Bicyclo[3.3.0]octene Framework

Abstract

We report a simple and highly stereocontrolled strategy toward the total synthesis of isoprostanes based on a bicyclic alpha,beta-epoxy ketone intermediate 6. Bicyclo[3.3.0]octene scaffold permitted stereodirection of reagents allowing stereoselective epoxidation, diastereoselective ketone reduction, and regioselective epoxide opening otherwise not accessible with a simple cyclopentene framework.

F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome

“…by guest, on May 9, 2018 www.jlr.org Downloaded from octene intermediate 1 ( 20,27 ). Using this precursor, we now report the synthesis of ent-7(RS)-F 2t -dihomo-IsoP, and 17-F 2t -dihomo-IsoP ( Scheme 1 ).…”

“…The mono-acetate intermediate 4 was obtained in fi ve steps from the keto-epoxide 1 on multigram scale, after successive reductions, protection, and enzymatic regioselective mono-acetylation ( Scheme 2 ) ( 20,27 ).…”

“…In the present study, we have examined the potential value of F 2 -dihomo--isoprostanes (F 2 -dihomo--IsoPs), oxidation products deriving from radical attack on adrenic acid (AdA) 22:4 n-6, a specifi c component of myelin, but also present in several organs and tissues, including the kidney and the adrenal glands (17)(18)(19), as an early marker of lipid peroxidation in RTT, by using the synthesis ( 20 ) of two series of AdA peroxidation products.…”

Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

“…The strategy was based on an easily accessible bicyclic precursor to obtain isoprostanoid derivatives [21], whereas a more refined strategy was used for the synthesis of the isomers, 4(RS)-4-F 4t NeuroP [22], 10-F 4t -NeuroP [23], and 14 (RS)-14-F 4t -NeuroP (unpublished data). The 13-F 4t -NeuroP was synthesized using another strategy [24].…”

The Handy Use of Brown’s P2‐Ni Catalyst for a Skipped Diyne Deuteration: Application to the Synthesis of a [D4]‐Labeled F4t‐Neuroprostane

“…[10] The synthesis of the required monoacetate 6 began from the enantiomerically enriched bicyclic keto-epoxide 8 (> 99 % ee), which was readily prepared in five steps from 1,3-cyclooctadiene (1,3-COD) (Scheme 3). [10,11] Stereoselective reduction of the ketone functionality of compound 8 with LiAlH 4 at low temperature led to the formation of an epoxy alcohol intermediate that underwent regioselective epoxide ring opening upon warming the reaction mixture from À78 8C to RT. Under these conditions, the cis-1,3-diol 9 was isolated in 75 % yield with an excellent diastereomeric ratio (d.r.)…”