23 6π-アザ電子環状反応における著しい活性化の実現を基盤とする新規ピリジン合成法の開発とレチナール異常代謝産物の合成(口頭発表の部)

抄録

The study on the reactivity of 1-azatrienes toward 6π-azaelectrocyclization is limited and the application of this reaction to the natural product synthesis is also very limited in the literature. This is presumably because the azaelectrocyclization process has been believed to require high temperature, and in addition, the method for preparation of 3-cis-1-azatrienes as precursors of the electrocyclization was not well established. During the course of our recent studies on the syntheses of the enzyme inhibitors and then on the elucidation of their inhibitory mechanism, we found that the (E)-3-carbonyl-2,4,6-trienal compounds inhibited the hydrolytic ability of phospholipase A_2 (PLA_2) by the formation of the dihydropyridine derivatives resulting from the reaction with the particular lysine residues of PLA_2 via 6π-electrocyclization of the intermediary Schiff base. Moreover, we found that the presence of both the C4 ester group and the double bond attached at C6 in 1-azatrienes significantly contributed to the acceleration of the azaelectrocyclization. In this conference, we disclose in detailed (1) the new and efficient method for the synthesis of the 3-cis-1-azatriene derivatives and the results of their 6π-azaelectrocyclization, and then we evidently concluded that the combination of the C4-carbonyl and the C6-olefin groups in 1-azatrienes actually contributed to the remarkable acceleration of the azaelectrocyclization based on the orbital interaction between HOMO of the olefin part and LUMO of the azadiene part under the reverse electron demanded mode. (2) This conclusion was supported by the molecular orbital calculation of the azatriene. Moreover, (3) the results obtained here were applied to the synthesis of the ocular age pigment A2-E, by focusing on two types of the new and efficient one-pot synthesis of substituted pyridines, which involve the sequence of (a) smooth 6π-azaelectrocyclization and dehydration, and (b) azaelectrocyclization and oxidation. The later sequence of the reactions is compatible with Nakanishi's hypothetical metabolic pathway of A2-E.