Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin
Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin
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DOI：
10.1021/jo202052a
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发表时间：
2011-12-16
影响因子：
3.6
通讯作者：
Ramirez, Antonio
中科院分区：
文献类型：
--
作者：
Jones, G. Scott;Savage, Scott A.;Ramirez, Antonio
二肽基肽酶-IV抑制剂沙格列汀（Onglyza）可以进行化学上有利的环化，形成相应的环脒。对这种转化的动力学和机制进行了研究，以开发一种商业合成方法，该合成方法提供的沙格列汀仅含有痕量的这种关键副产物。这项工作的重要发现是一个深刻的溶剂效应的识别和自催化途径的测定。这两种现象都是由涉及质子转移的过渡结构引起的。
The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer.