A multistage, one-pot procedure mediated by a single catalyst:: A new approach to the catalytic asymmetric synthesis of β-amino acids
A multistage, one-pot procedure mediated by a single catalyst:: A new approach to the catalytic asymmetric synthesis of β-amino acids
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DOI：
10.1021/jo034150e
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发表时间：
2003-07-25
影响因子：
3.6
通讯作者：
Lectka, T
中科院分区：
文献类型：
--
作者：
Hafez, AM;Dudding, T;Lectka, T
报道了一种制备β -氨基酸（特别是β -取代的天冬氨酸衍生物）的催化不对称方法。金鸡纳生物碱催化剂苯甲酰奎宁（BQ）在一个反应容器中介导多达五个不同的反应途径。在催化剂的作用下，由n -酰基- α -氯甘氨酸酯和酸氯化物制备了高光学富集的β -取代天冬氨酸衍生物。这种方法也适用于合成含有β -取代天冬氨酸单元的小多肽，包括抗生素溶菌素的非天然片段。在该体系中加入路易斯酸可以加快反应途径中特定步骤的速率。该反应的机理方面，如亚胺的形成和刘易斯酸与β -内酰胺中间体的螯合，通过IR、NMR和其他物理数据的比较进行了研究。
A catalytic asymmetric procedure for the preparation of beta-amino acids (specifically beta-substituted aspartic acid derivatives) is reported. The cinchona alkaloid catalyst benzoylquinine (BQ) mediates up to five distinct steps of a reaction pathway, all in one reaction vessel. The products of this reaction, highly optically enriched beta-substituted aspartic acid derivatives, were prepared from N-acyl-alpha-chloroglycine esters and acid chlorides in the presence of the catalyst. This approach was also amenable to the synthesis of small polypeptides containing beta-substituted aspartic acid units, including a non-natural fragment of the antibiotic lysobactin. The addition of Lewis acids to this system was found to accelerate the rate of specific steps in the reaction pathway. Mechanistic aspects of this reaction, such as imine formation and Lewis acid chelation to the beta-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.