P-35 C-1027クロモフォアの全合成研究(ポスター発表の部)

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C-1027 is a member of antitumor chromoproteins. It is composed of the apoprotein and the labile enediyne chromophore 1. The C-1027 chromophore 1 quickly aromatizes via Masamune-Bergman cyclization at ambient temperature, generating p-benzyne biradical 2 that exerts its biological activity by abstracting hydrogen from DNA. This chemical instability and its complex structure distinguish 1 as a challenging target for the total synthesis. In this paper, we report the synthesis of the C-1027 chromophore framework via atropselective macrolactonization as well as construction of bicyclo[7.3.0]dodecatrienediyne structure. First, we synthesized the seco-acids (5, 16, 17) by assembly of the three fragments (6, 7, 8). Successful atropselective macrolactonization was realized by utilizing long-range steric interactions of the protective groups of the 1,5-diol of 5. Subsequently, LiN(TMS)_2/CeCl_3-promoted acetylide addition to aldehyde in the setting of a rigid macrocycle formed the target nine membered ring system having a highly strained diyne (22→4). Next, we developed a general and efficient route to the reactive trienediyne core model of 1, utilizing the selenoxide elimination and the epoxide deoxygenation with WCl_6/n-BuLi to build the cyclopentadiene and enediyne structures, respectively. Despite the successful model experiments, application of the same procedure to the chromophore framework was abandoned, because synthesis of C4,5-epoxide 33 was unsuccessful. On the other hand, treatment of C4,5-dimesylate 34 with SmBr_2 produced aromatized C-1027 chromophore framework 36 in high yield. Further studies on the total synthesis of 1 are currently underway.
天然有機化合物討論会の論文
2005-09-15

P-35 C-1027クロモフォアの全合成研究(ポスター発表の部)

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