TOTAL SYNTHESIS OF SPATOL AND OTHER SPATANE DITERPENES

Total syntheses of three spatane diterpenes stoechospermol (1), 5(R),15(R),18-trihydroxyspata-13,16(E)-diene (2), and (+)-spatol (3) were accomplished from a common intermediate, diol 7. The total synthesis established as R the absolute configuration at the 15-position in 2. Novel stereospecific transformations of 2,3-epoxy-1,4-diols into vicinal diepoxides were demonstrated and exploited for assembling the sensitive allylic diepoxide in the side chain of spatol. This new synthetic method allows the conversion of both 1,2-threo-2,3-trans- and 1,2-erythro-2,3-trans-2,3-epoxy-1,4-diols into vicinal 1,2-cis-2,3-erythro-1,3-diepoxides. Unexpected stability toward hydroxide anion was found for the allylic diepoxide functional array. This observation provides presumptive evidence that acid catalysis is operative in the epoxide cleaving substitution reaction of spatol by the weakly nucleophilic chloride anion that gives chlorohydrin 4. A proclivity for erythro-selective epoxidation of allylic silyl ethers was found. The utility of C-silyl substituents for reversing this stereoselectivity, i.e., favoring threo-selective epoxidation of allylic silyl ethers, was established.