Synthesis and cellular effects of cycloterpenals: Cyclohexadienal-based activators of neurite outgrowth

An unusual class of diterpenoid natural products, ‘cycloterpenals’ (with a central cyclohexadienal core), that arise in nature by condensation of retinoids and other isoprenes, have been isolated from a variety of organisms including marine sponges as well as from the human eye. A milk whey protein has also demonstrated the formation of a cycloterpenal derived from β-ionylidineacetaldehyde. Here, we generate a synthetic library of these molecules where we detail reaction conditions required to effect cross condensation of α,β-unsaturated aldehydes as opposed to homodimerization. The ability of this class of molecules to activate neurite outgrowth activity is reported.

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