Nikolić Dejan, Macias Carmen, Lankin David C, van Breemen Richard B
Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL, 60612-7231, USA.
Rapid Commun Mass Spectrom. 2017 Sep 15;31(17):1385-1395. doi: 10.1002/rcm.7915.
Phenethylamides are a large group of naturally occurring molecules found both in the plant and animal kingdoms. In addition, they are used as intermediates for the synthesis of pharmaceutically important dihydro- and tetrahydroisoquinolines. To enable efficient characterization of this class of molecules, a detailed mass spectrometric fragmentation study of a broad series of analogs was carried out.
The test compounds were synthesized using standard methods for amide bond formation. Low-energy high-resolution tandem mass spectra were acquired on a hybrid quadrupole/time-of-flight mass spectrometer using positive ion electrospray ionization.
A total of 26 analogs were investigated in the study. Fragmentation of phenethylamides was found to proceed via intermediate ion-neutral complexes. The complexes can break down via multiple pathways including dissociation, proton transfer, Friedel-Crafts acylation, and single electron transfer. The relative contribution of each of these pathways strongly depends on the structure of the coupling amine and acid.
A general scheme for the fragmentation of phenethylamides was developed. This study further extends the knowledge base of the ion-neutral complex by discovering Friedel-Crafts acylation as a novel reaction. The strong influence of minor structural modifications on the fragmentation patterns highlights the importance of testing many analogs in order to fully predict a fragmentation pattern of a particular class of molecules.
苯乙酰胺是一大类在植物界和动物界均有发现的天然存在的分子。此外，它们还用作合成具有重要药学意义的二氢和四氢异喹啉的中间体。为了能够对这类分子进行高效表征，我们对一系列广泛的类似物进行了详细的质谱裂解研究。
使用形成酰胺键的标准方法合成测试化合物。在混合四极杆/飞行时间质谱仪上采用正离子电喷雾电离采集低能量高分辨率串联质谱。
本研究共考察了26种类似物。发现苯乙酰胺的裂解通过中间离子-中性复合物进行。这些复合物可通过多种途径分解，包括解离、质子转移、傅克酰基化和单电子转移。这些途径中每条途径的相对贡献强烈取决于偶联胺和酸的结构。
制定了苯乙酰胺裂解的通用方案。本研究通过发现傅克酰基化作为一种新反应，进一步扩展了离子-中性复合物的知识库。微小结构修饰对裂解模式的强烈影响突出了测试许多类似物以充分预测某一特定类分子裂解模式的重要性。
