Flexible Approach to (5Z,9Z)-Dienoic Fatty Acids Relevant to the Synthesis of Demospongic Acids and Related Natural Products

A flexible and efficient synthesis of the potent human topoisomerase inhibitor (5Z,9Z)-eicosa-5,9-dienoic acid was explored; the presented method represents a generally applicable approach towards demospongic acids and related natural products. Key steps of the synthesis involve chemoselective hydroboration, Corey-Fuchs alkynylation, Z-selective Lindlar reduction, tetrapropylammonium perruthenate catalyzed direct oxidation of a primary alcohol to the corresponding acid, and Arndt-Eistert homologation. Thus, the total synthesis of (5Z,9Z)-eicosa-5,9-dienoic acid was achieved in 10 steps in an overall yield of 20%.