羥基化Rollicosin類似物之合成研究

Rollicosin (11) 是由番荔枝科植物Rollinia mucosa Bill 所分離出，並展現了對腫瘤細胞的優越活性，我們設計合成一個羥基化的 Rollicosin 類似物15，且探討其結構與活性的關係。 Rollicosin 類似物15 之合成可藉由金屬Pd 催化化合物56 與碘化物57 進行偶合反應。化合物56 的合成以5-hexen-1-ol 為起始物，經由6 個步驟，包含一及醇的碘化反應，與化合物18 進行烷基化反應，不對稱雙醇化，環氧化，格林納開環加成即可得到化合物56。內酯化合物57 是由5-己炔-1-醇為起始物的7 個步驟，經由TMSCl 保護末端炔，PCC 氧化醇形成醛，醛基經由溴鎂乙烯加成，Claisen 重排反應，不對稱雙醇化，去矽烷反應，Morpholine 碘化即可得到化合物57。化合物56 及化合物57 後續的合成步驟仍在研究中。

關鍵字

Rollicosin類似物

並列摘要

Rollicosin (11) was isolated from annonaceous plant, Rollina mucosa, which exhibited potent growing inhibition ability against several human cancer lines. To explore the SARs of rollicosin, a hydroxylated rollicosin analog 15 was designed and synthesized for the biological evaluation. The synthesis of compound 15 was based on a palladium catalyzed coupling of the lactone 56 and iodide 57. The synthesis of compound 56 started from 5-hexen-1-ol in six steps, including iodination of the primary alcohols, sharpless asymmetric dihydroxylation of the olifen, epoxidation of the diol, alkylation of the epoxide with lactone 18, ring opening reaction of the epoxide and desilylation gave lactone 56. The preparation of the iodide 57 was accessed from 5-penty-1-ol in seven steps, including protection of the terminal acetylene, oxidation of the alcohol, vinyl magnesium bromide addition of the aldehyde, ortho-acetate claisen rearrangement, asymmetric dihydroxylation, deprotection of the acetylene and iodination gave the iodide 57. The conversion of compound 56 and 57 to the target molecule is still under investigation.