Synthesis of anacardic acids

Abstract The anacardic acids 1–11 , isolated from various plants, were synthesized by a new general method. Reaction of the methyl alkynoates 12–18 with 1‐methoxy‐1,4‐cyclohexadiene at 200°C afforded directly the methyl 2‐methoxybenzoates 19–25 with long chain substituents in 6‐position in 74–85% yield. The dienophiles 12–16 were prepared by pyrolysis of the corresponding acylphosphoranes 26–30 , the dienophiles 17 and 18 by methoxycarbonylation of the corresponding alkynes 31 and 32 via the hydroxy esters 33 and 34. Demethylation of 19–23 with All 3 gave the methyl salicylates 35–39 which could be hydrolized to the anacardic acids 1–4 and 7. Hydrolysis of 24 and 25 provided the hydroxy acids 40 and 41 , which were converted by treatment with CBr 4 /PPh 3 into the acids 42 and 43 bearing bromoalkyl side chains. These were transformed into 44–47 by reaction with 1‐hexynyllithium and 1‐octynyllithium. Stereoselective hydrogenation of 44–47 gave 48–51 with (Z)‐alkene side chains. In a similar approach 42 was converted into 52 and then into 53 , which gave upon treatment with 1‐pentynylmagnesium bromide or 1‐heptynylmagnesium bromide the acids 54 and 55 with alkadiyne side chains. Stereoselective hydrogenation provided 56 and 57 with (Z,Z)‐alkadiene side chains. The 2‐methoxy group in 48–51, 56, 57 was demethylated by treatment with All 3 to give the anacardic acids 5, 6, 8–11 .