4 大員環エノラートを鍵中間体とするSarcophytol AおよびSteroid骨格の合成と理論計算(口頭発表の部)

抄録

Macrocycles have the π-orbitals of olefins oriented in the plain of the ring to minimize the transannular nonbonded repulsions. Therefore in a macrocyclic system, the inter- and intramolecular reactions should proceed exclusively from one side (Fig. 1). For example, intermolecular reaction proceeds from the outside of the ring, and intramolecular reaction takes place only through the interior side of π-orbitals. There are extensive studies on the stereocontrol of enolate reactions in normal five, six membered ring and acyclic systems. However, it is quite difficult to predict the stereoselectivity of the macrocyclic enolate reactions because of their many conformational possibility. It would be an important advance if these problems could be solved. Here we report the efficient total synthesis of sarcophytol A, a simple cembranoid that has been claimed to have potent anticancer activity, and the construction of steroid skeleton, based on the macrocyclically controlled reactions of enolates. We also describe the conformational analysis of the large membered enolates for the prediction of the stereoselectivity of the enolate reactions. The syntheses of sarcophytol A and steroid skeleton feature noteworthy methods including the following: 1) Conjugate addition of dimethylcuprate with the exo-enone 14 followed by β-elimination of MOMO group providing the E,Z-endo-dienone system of sarcophytol A, stereoselectively. 2) Conformational analysis of macrocyclic systems by Multiconformer and Monte Carlo method to predict the stereoselectivity of the β-elimination. 3) Development of dianion method for the construction of large memberd ring system.