Towards the Synthesis of the Neurofurans
Date
2009-05
Authors
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Publisher
University of Delaware
Abstract
Derived from endogenous docosahexaenoic acid, neurofurans (nFs) are produced in mammalian brain tissue through nonenzymatic free radical oxidation pathways, culminating in 512 enantiomerically pure diastereomers. To achieve enantioselective syntheses of individual nFs, a strategy involving a tunable tetrahydrofuran intermediate was developed. The four stereocenters of the THF core were set by choice of ligands during the Sharpless epoxidation and dihydroxylation steps. Subsequent cascade cyclization delivered the key tetrahydrofuran intermediate as a single enantiomer. The THF core’s design also allows for diversity in upper and lower sidechain construction, thus being flexible enough to allow the synthesis of each of the many different nFs. This strategy was applied towards the synthesis of AC-Δ^9-5-NeuroF and its C-11 epimer.