Total Synthesis of the Enantiomer of the Furanocembrane Rubifolide.

Abstract

The total synthesis of 57, the enantiomer of the marine furanocembrane rubifolide (3), is described starting from (S)-(-)-perillyl alcohol (5). The successful route proceeded by oxidative cleavage of 5 to ester aldehyde 30 which was protected, reduced, and homologated to the acetylene 34, the left-hand segment of the synthetic target. Addition to the right-hand aldehyde 39 afforded alcohol 40. The carbonate derivative 41 was converted to the allenylstannane aldehyde 44, which cyclized upon treatment with BF(3).OEt(2). Oxidation with the Dess-Martin periodinane reagent followed by treatment with Et(3)N yielded allenone 45. Allenone 45 cyclized to furan 46 in the presence of catalytic AgNO(3) on silica gel. Brief exposure to p-TsOH effected elimination of the OMOM ether, affording the diastereomeric (Z)-vinylfuran carbonates 47 and 49. Saponification of the former led to alcohol 48, which was converted to the final product by sequential treatment with (CF(3)CO)(2)O, then Pd(PPh(3))(4) and CO in THF-H(2)O, and then AgNO(3) on silica gel. The resulting product, 57, was identical to natural rubifolide on the basis of spectral comparison. The optical rotation was equal and opposite in sign to that of the natural material. A second, but unsuccessful approach is also described.