Synthesis of novel tri‐ and tetrasubstituted C₁₈ furan fatty esters

Abstract

A methylene-interrupted C18 keto-acetylenic fatty ester (methyl 12-oxo-9-octadecynoate) was obtained from methyl ricinoleate by bromination-dehydrobromination followed by oxidation. Reaction of methyl 12-oxo-9-octadecynoate with bis(benzonitrile) palladium(II) chloride, allyl bromide, or methyl-allyl bromide furnished methyl 8-[5-hexyl-3-allyl-furan-2-yl]-octanoate (1, 56%) or methyl 8-15-hexyl-3-(2-methyl-allyl)-furan-2-yl]-octanoate (2, 55%). Reaction of methyl 12-oxo-11-chloro- or 11-fluoro-9-octadecynoate (prepared from methyl santalbate--methyl 11-E-9-octadecynoate, found in sandalwood, Santalum album, seed oil) with bis(benzonitrile) palladium(II) chloride gave methyl 8-(4-chloro-5-hexyl-furan-2-yl)-octanoate (3, 59%) or methyl 8-(4-fluoro-5-hexyl-furan-2-yl)-octanoate (4, 50%), respectively. And when methyl 12-oxo-11-chloro- or 11-fluoro-9-octadecynoate was treated with a mixture of bis(benzonitrile) palladium(II) chloride, allyl bromide, or methyl-allyl bromide, the reaction yielded tetrasubstituted C18 furan derivatives, viz., methyl 8-(3-allyl-4-chloro-5-hexyl-furan-2-yl)-octanoate (5, 54%), methyl 8-[4-chloro-5-hexyl-3-(2-methyl-allyl)-furan-2-yl]-octanoate (6, 54%), methyl 8-(3-allyl-4-fluoro-5-hexyl-furan-2-yl)-octanoate (7, 10%), and methyl 8-14-fluoro-5-hexyl-3-(2-methyl-allyl)-furan-2-yl]-octanoate (8, 10%). The presence of a fluorine atom in the furan derivatives 4, 7, and 8 was readily characterized by the appearance of doublets for carbon nuclei, which were coupled to the fluorine atom in the 13C NMR spectra. All furan fatty derivatives from this work were characterized by NMR spectroscopic and mass spectrometric analyses. The yields of compounds 7 and 8 were very low (10%) despite attempts to improve the procedure by increasing the amounts of the reactants and catalyst.

Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus

“…To examine the anti-inflammatory activity, a sufficient amount of pure material was required. Although several groups previously reported the synthesis of F-acid (43)(44)(45)(46)(47)(48)(49), the synthetic route required many steps. To prepare these fatty acids easily, a shark metabolite was selected as the starting material, because sharks are commercially available for consumption in the northeast area of Japan.…”