This proposal describes the use of intramolecular diyl trapping reactions in the synthesis of linearly fused tricyclopentanoids and hydroazulenes. We have shown that the intramolecular reactions predictably proceed with a very high degree of regio- and stereoselectivity which can be controlled to achieve the desired ring junction stereochemistry in polyfused ring systems. Specific tricyclopentanoid target molecules destined to be synthesized using this methodology include the biosynthetic precursor of the coriolins and hirsutic acid namely, hirsutene, as well as the coriolins, and the antibiotic and anticancer agent diketocoriolin B. The possibility of effecting asymmetric induction in tricyclopentanoid synthesis, with the ultimate objective being a total synthesis of optically active diketocoriolin B, is to be activey investigated. It is shown herein that a commmon intermediate could be used in the synthesis of each of the target molecules in both chiral and achiral forms. Finally, the synthetic methodology described should allow a detailed structure activity relationship study of diketocoriolin B, it's synthetic precursors, and it's derivatives to be conducted. The use of an intramolecular diyl trapping reacting, proceeding from a common intermediate, to synthesize the pseudoguaianolides confertin and the anticancer agent damsin is described. We intend to explore the possibility of converting the common intermediate to C9 oxygenated pseuoguaianolides possessing a helenanolide relationship between the C5 and C10 methyl groups, our ultimate, long term objective being the synthesis of the C9 oxygenated anticancer agents fastigilin B and C, radiatin, and multiradiatin.
NIH ExPorter
NIH ExPorter