Laboratory of Synthesis and Natural Products (LSPN), Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH, 5304, 1015, Lausanne, Switzerland.
School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, P. R. China.
Angew Chem Int Ed Engl. 2023 Jan 2;62(1):e202213831. doi: 10.1002/anie.202213831. Epub 2022 Dec 1.
We report herein an asymmetric Pictet-Spengler reaction of α-ketoesters. In the presence of a catalytic amount of simple alanine-derived squaramide and p-nitrobenzoic acid, reaction of tryptamines with methyl 2-oxoalkanoates afforded the corresponding 1-alkyl-1-methoxycarbonyl tetrahydro-β-carbolines (THBCs) in high yields and ee values. A primary kinetic isotope effect (KIE=4.5) using C2-deteurium-labelled tryptamine indicates that rearomatization through deprotonation of the pentahydro-β-carbolinium ion could be the rate- and enantioselectivity-determining step. A concise enantioselective total synthesis of (+)-alstratine A, a hexacyclic cagelike monoterpene indole alkaloid, featuring this reaction as a key step, was subsequently accomplished. Remeasurement of the [a] value of the natural product indicates that natural alstratine A is dextrorotatory rather than levorotatory as it was initially reported in the isolation paper.
我们在此报告了α-酮酯的不对称皮克特-斯彭格勒反应。在少量简单丙氨酸衍生的琥酰胺和对硝基苯甲酸的存在下，色胺与甲基 2-氧代链烷酸酯反应以高收率和 ee 值得到相应的 1-烷基-1-甲氧基羰基四氢-β-咔啉（THBC）。使用 C2-氘标记的色胺的一级动力学同位素效应（KIE=4.5）表明，通过五氢-β-咔啉鎓离子的去质子化进行再芳构化可能是速率和对映选择性决定步骤。随后，以该反应为关键步骤，完成了（+）-阿斯特拉汀 A 的简洁对映选择性全合成，（+）-阿斯特拉汀 A 是一种六环笼状单萜吲哚生物碱。重新测量天然产物的[a] 值表明，天然阿斯特拉汀 A 是右旋而不是最初在分离论文中报道的左旋。
