The first enantioselective total synthesis and structural reassignment of (−)-thelepamide, a cytotoxic tetraketide–amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre’s organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal–hemiacetal moiety. The corrected structure was confirmed by NMR–DFT analysis.

中文翻译：

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通过催化剂控制的半胱氨酸衍生物的1,4-加成合成Thelepamide和Thelepamide的结构修改

据报道，首次从海洋蠕虫Thelepus crispus获得了具有细胞毒性的四酮化合物-氨基酸-（-）-thelepamide的对映选择性全合成和结构重新分配。收敛方法可从四个简单的构建基元中以六个步骤访问所有的lepamide非对映异构体。合成的关键特征包括应用Melchiorre的有机催化thia-Michael反应和超声辅助的N，O-乙缩醛-半缩醛部分的组装。通过NMR-DFT分析确认了校正后的结构。