Synthesis and biological activity of α,β,γ,δ-unsaturated aldehydes from diatoms

a,beta,gamma,delta-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 alpha,beta,gamma,delta-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 stercochemistry 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 omega-oxo acids with conjugated double systems. In contrast, the double bond geometry has no influence on biological activity. The alpha,beta-unsaturated 2E-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. (C) 2003 Elsevier Science Ltd. All rights reserved.