Biology and chemistry of neuroprostanes. First total synthesis of 17-A4-NeuroP: Validation of a convergent strategy to a number of cyclopentenone neuroprostanes

• Validation of a general synthetic strategy to A4-NeuroPs.
• Synthesis of 17-A4-NeuroP.
• 17-A4-NeuroP adduct with GSH thiol group.
• Stereoselective semi-hydrogenation of a skipped diyne to the corresponding1,4-diene.
• Diastereoselective aspects of the Julia-Kocienski reaction.

In a process associated with ageing and neurodegeneration, radical peroxidation of docosahexaenoic acid (DHA) in neurons affords a multitude of prostaglandin-like neuroprostanes in a non-regioselective and non-stereoselective manner. In this paper, the synthesis of racemic 17-A4-NeuroP and 14-A4-NeuroP validated a general approach to several regioisomeric cyclopentenone A4- and J4-NeuroPs needed for biological tests. In preliminary experiments 17-A4-NeuroP, in analogy with 14-A4-NeuroP, readily adducted GSH free thiol, suggesting a similar mechanism of action for biological activity.

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