Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes
Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes
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DOI：
10.1021/ja058216u
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发表时间：
2006-03-08
影响因子：
15
通讯作者：
Koide, K
中科院分区：
文献类型：
--
作者：
Albert, BJ;Sivaramakrishnan, A;Koide, K
FR 901464是一种有效的抗癌剂，可调节癌基因和肿瘤抑制基因的转录。FR 901464的收敛对映选择性合成在13个线性步骤中完成。合成方法的核心是二烯-烯交叉烯烃复分解反应，以生成C6−C7烯烃，而不使用保护基团作为最终偶联。其他关键反应包括Zr/Ag促进的炔基化以固定C4立构中心，温和的化学选择性Red-Al还原，立体选择性Mislow− Evans型[2，3]-σ迁移重排以安装C5立构中心，Carreira不对称炔基化以产生C4'立构中心，以及高效的闭环复分解-烯丙基氧化序列以形成不饱和内酯。
FR901464 is a potent anticancer agent that regulates the transcription of oncogenes and tumor suppressor genes. A convergent enantioselective synthesis of FR901464 was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6−C7 olefin, without the use of protecting groups, as the final coupling. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a stereoselective Mislow−Evans-type [2,3]-sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4‘ stereocenter, and a highly efficient ring-closing metathesis−allylic oxidation sequence to form an unsaturated lactone.