Asymmetric Construction Of Eudesmane Skeleton By Diels-Alder Reaction And Synthesis Of2-substituted,(E)-1,3-disubstituted Conjugated Butadiene

Eudesmane sesquiterpenoids, with a variety of biological activities and medical values, are very important natural products. Synthetic methodologies for these compounds have been actively studied so far, but few of universal, efficient and stereochemically controllable methods were developed, which are not favorable to the synthesis of versatile eudesmane derivatives and analogs that used in bioactivity tests and structure-activity relationship analysis.In this thesis, retrosynthetic analysis of Carainterol A, a eudesmane sesquiterpenoid, revealed that the construction of the bicyclic skeleton of the compound could be accomplished by intermolecular asymmetric Diels-Alder cyclization in high regio-and stereo-selectivity. Due to its excellent versatility, Diels-Alder reaction has been widely applied in total synthesis of many natural products. The author has designed and synthesized a series of substituted cyclohexenone and benzoquinone as dienophiles, and1,3-disubstituted congjugated butadiene as dienes to form the eudesmane skeleton. The asymmetric cyclization was catalyzed by two kinds of chiral Lewis acid, Ti-TADDOL and Oxazaborolidine, which derived from tartaric acid and diphenyl(pyrrolidin-2-yl)methanol respectively. Thus, the formation of bicyclic skeleton could be achieved in one step, and two kinds of key intermediates have been obtained in modest stereoselectivity. The key intermediate ZYC29was synthesized in yield of83%with60%ee value.We also found that2-substituted and (E)-1,3-disubstituted conjugated butadiene were very useful in forming natural products with multi-cyclic skeletons. But there still lacks a convenient, efficient and universal access to such compounds. So we began to develop a sythetic methodology on these congjugated dienes.The strategy of our synthesis was "A+B", and Mannich reaction, Wittig olefination and Julia olefination were used to afford a variety of conjugated butadienes containing diverse substituents in two steps. The stereochemistry of the methodology led to E isomers mainly, which met the needs of Diels-Alder reaction exactly. Six2-substituted conjugated butadienes and seven (E)-1,3-disubstituted conjugated butadienes were successfully synthesized.