Synthesis of the novel (±)-2-methoxy-6-icosynoic acid--a fatty acid that induces death of neuroblastoma cells.

The first total synthesis for the novel fatty acid (±)-2-methoxy-6-icosynoic acid was accomplished in seven steps and in a 14% overall yield starting from 2-(4-bromobutoxy)-tetrahydro-2H-pyran. The title compound displayed an EC50=23±1 μM against the human SH-SY5Y neuroblastoma cell line and an EC50=26±1 μM against the human adenocarcinoma cervix cell line (HeLa) after 48 h of exposure. The corresponding non-methoxylated analog 6-icosynoic acid did not display cytotoxicity (EC50>500 μM) toward the studied cell lines as well as the 2-methoxyicosanoic acid (EC50>300 μM). The critical micelle concentration (CMC=20-30 μM) for the (±)-2-methoxy-6-icosynoic acid was also determined. It was found that α-methoxylation decreases the CMC of a fatty acid.