Synthesis and biological activity of alpha,beta,gamma,delta- unsaturated aldehydes from diatoms

Abstract α,β,γ,δ-Unsaturated aldehydes have gained increasing attention since 2,4-decadienal and 2,4,7-decatrienal were isolated from the diatom Thalassiosira rotula and characterized as cell antiproliferative metabolites. Structurally related α,β,γ,δ-unsaturated aldehydes were found in this alga as well as in other diatom species. We present a short and universal synthesis of this compound class along with a structure–activity study of the potential to inhibit sea urchin egg cleavage. Pd 0 - or Co II -mediated cross coupling of 5-iodo-penta-2,4-dienal with organo-zincates allows the fast and flexible synthesis of numerous aldehydes from this universal precursor. The stereochemistry of the double bond system of the precursor was preserved during the coupling. Bioassays showed that the polarity of the side chain is important for antiproliferative activity with 2,4-decadienal as the most active compound tested compared to the shorter-chain aliphatic homologues and to ω-oxo acids with conjugated double systems. In contrast, the double bond geometry has no influence on biological activity. The α,β-unsaturated 2 E -decenal was also highly active, while activity diminished in the case of saturated aldehydes of similar chain length. 1-Decanol, 2-decanone and decanoic acid were not active.