Kuo Chih-Hung, Hsieh Wen-Tsai, Yang Ya-Hsu, Hwang Teng-Li, Cheng Yu-Shan, Lin Yuya A
Department of Chemistry, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
J Org Chem. 2024 Apr 5;89(7):4958-4970. doi: 10.1021/acs.joc.4c00162. Epub 2024 Mar 24.
Cesium carbonate promoted direct amidation of unactivated esters with amino alcohols was developed without the use of transition-metal catalysts and coupling reagents. This method enabled the synthesis of several serine-containing oligopeptides and benzamide derivatives with yields up to 90%. The methodology proceeds under mild reaction conditions and exhibits no racemization for most naturally occurring amino acid substrates. The reaction demonstrates good compatibility with primary alkyl and benzyl esters and broad tolerance for a range of amino acid substrates with nonpolar and protected side chains. The hydroxy group on the amine nucleophile was found to be critical for the reaction to be successful. A likely mechanism involving cesium coordination to the substrates enabling the subsequent proximity-driven acyl transfer was proposed. The practicality of this approach was demonstrated in the preparation of a biologically active nicotinamide derivative in a reasonable yield.
开发了碳酸铯促进未活化酯与氨基醇直接酰胺化反应的方法，该方法无需使用过渡金属催化剂和偶联试剂。此方法能够合成几种含丝氨酸的寡肽和苯甲酰胺衍生物，产率高达90%。该方法在温和的反应条件下进行，对于大多数天然存在的氨基酸底物不发生消旋化。该反应对伯烷基酯和苄酯表现出良好的兼容性，对一系列具有非极性和受保护侧链的氨基酸底物具有广泛的耐受性。发现胺亲核试剂上的羟基对于反应成功至关重要。提出了一种可能的机理，即铯与底物配位，从而实现随后的邻近驱动的酰基转移。该方法的实用性在以合理产率制备生物活性烟酰胺衍生物中得到了证明。
