TOTAL SYNTHESIS OF THE ENANTIOMER OF THE FURANOCEMBRANE RUBIFOLIDE

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 acet ylene 34, the left-hand segment of the synthetic target. Addition to t he right-hand aldehyde 39 afforded alcohol 40. The carbonate derivativ e 41 was converted to the allenylstannane aldehyde 44, which cyclized upon treatment with BF3 . OEt2. Oxidation with the Dess-Martin periodi nane reagent followed by treatment with Et3N yielded allenone 45. Alle none 45 cyclized to furan 46 in the presence of catalytic AgNO3 on sil ica gel. Brief exposure to p-TsOH effected elimination of the OMOM eth er, 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 (CF3CO)(2)O, then Pd(P Ph3)(4) and CO in THF-H2O, and then AgNO3 on silica gel. The resulting product, 57, was identical to natural rubifolide on the basis of spec tral comparison. The optical rotation was equal and opposite in sign t o that of the natural material. A second, but unsuccessful approach is also described.