P-80 強い細胞毒性をもつKulokekahilide-2およびその類似体の合成(ポスター発表の部)

概要

論文の詳細を見る
We previously reported the isolation, structural elucidation, and biological activity of kulokekahilide-2 (1). Kulokekahilide-2 contains five amino acids - L-Ala, D-Ala, L-Ile, MeGly, and L-MePhe-and two hydroxy acids, D-2-hydroxyisocaproic acid (D-Hica) and (5S,6S,7S,2E,8E)-2,6,8-trimethyl-5,7-dihydroxy-2,8-decadienoic acid (Dtda), the structure is reminiscent of aurilide (2) from Japanese mollusk Dolabella auricularia. However, when the structures of 1 and 2 are compared, the stereochemistry of some of the residues is reversed. In order to confirm the stereochemistry of 1 and to develop a method for obtaining this compound in larger amounts to allow further investigation of its bioactivity, a total synthesis of 1 was attempted. We found that macrolactonization, the final step in the synthesis, was difficult and resulted in the formation of 43-epimer (1a). In contrast, macrolactamization of the corresponding amino acid at the last step proceeded without racemization to afford the product 1b, whose stereochemistry is identical to that of the proposed structure of natural 1. In our surprise, however, the NMR spectral data of 1b did not match those of the natural 1, and potent cytotoxicity was observed for neither 1a nor 1b. The proposed structure of 1 was incorrect. Therefore, the correct structure is confirmed by the synthesis of several analogues.
天然有機化合物討論会の論文
2007-08-24