A Divergent Synthesis of the Δ¹³-9-Isofurans

Abstract

A stereodivergent total synthesis of the Δ 13 -9-isofurans has been developed. The four core substituted tetrahydrofurans were prepared by the Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation followed by cascade cyclization. The relative configuration at C-8 was inverted by oxidation followed by immediate L-selectride reduction. The relative configuration of the C-15 diastereomers were assigned by (S)-Binol/LAH/EtOH reduction of the corresponding enone. This synthesis of the Δ 13 -9-isofurans will provide sufficient material for further investigation of their biological activity.

Total Syntheses and In Vivo Quantitation of Novel Neurofuran and Dihomo‐isofuran Derived from Docosahexaenoic Acid and Adrenic Acid

“…In the white matter of the brain, adrenic acid (AdA, C22:4 n-6) is most abundant, and leads to the formation of dihomo-isofuran (dihomo-IsoF) metabolites. [10][11][12] More recently, Zanoni and co-workers used Trost asymmetric allylic alkylation for the synthesis of an alkenyl-NeuroF. [9] Besides being potential biomarkers, such metabolites could provide pharmacological properties yet to be discovered.…”

“…The first syntheses realized by Taber et al. allowed the access to arachidonic acid derived alkenyl‐ and enediol‐type IsoFs (Δ 13 ‐9‐IsoFs, ent ‐SC‐Δ 13 ‐8‐IsoF and epi ‐ ent ‐SC‐Δ 13 ‐8‐IsoF), whereas the furan core was obtained by diol epoxide benzenesulfonate cyclization 10–12. More recently, Zanoni and co‐workers used Trost asymmetric allylic alkylation for the synthesis of an alkenyl‐NeuroF 13.…”

Synthesis and discovery of phytofurans: metabolites of α-linolenic acid peroxidation

“…Three strategies have been reported for the synthesis of this family of natural products by the group of Taber (IsoFs), [7][8][9] Zanoni-Vidari (NeuroFs) 10 and our group (dihomo-IsoFs and NeuroFs). 11,12 We report herein on the development of a novel and powerful strategy for the synthesis of all members of this family of targets and their derivatives.…”

History of Chemical Routes towards Cyclic Non-Enzymatic Oxygenated Metabolites of Polyunsaturated Fatty Acids

“…In 2009, they were able to control the stereochemistry of the last asymmetric carbon by a slight modification of the substrate. 59 The α lateral chain insertion by HWE olefination gives the possibility to reduce the enone stereoselectively. The strategy of the Taber group is also efficient for the synthesis of enediol IsoFs.…”