Optimised total syntheses of the F-furan fatty acids F5 and F6 and some deuterated derivatives

Abstract

Optimised syntheses of F5- and F6-furan fatty acids 2 and 3 are described in full. Key steps include furan formation from a single 3-alkyne-1,2-diol 6 using 5-endo-dig cyclisations triggered by silver(I) nitrate or iodine. Introduction of the final carboxylic acid function and one-carbon homologation were achieved by cross metathesis with benzyl acrylate and hydrogenation. Iodine-methyl exchange of intermediate iodofurans was achieved by direct treatment with methyl lithium, which gave trideuterated derivatives 16 of the F6 acid by using CD3Li. The two acids 2 and 3 proved very unstable; thus, if samples are to be stored for extended periods, this should be as an ester and not as the free acids. This instability does raise questions regarding previously determined levels of these free acids (and perhaps some of their structurally close relatives) in various natural sources.