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A Scalable Total Synthesis of the Antitumor Agents Et-743 and Lurbinectedin
Weiming He1, Zhigao Zhang1, Dawei Ma1
1Interdisciplinary Center on Biology and Chemistry & State Key Laboratory of Bioorganic & Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.
Abstract:
An efficient and scalable approach is described for the total synthesis of the marine natural product Et-743 and its derivative lubinectedin, which are valuable antitumor compounds. The method delivers 1.6 % overall yield in 26 total steps from Cbz-protected (S)-tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light-mediated remote C-H bond activation to assemble a benzo[1,3]dioxole-containing intermediate.
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