Dejan Nikolić1, Carmen Macias1, David C Lankin1, Richard B van Breemen1. 1. 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.
Abstract
RATIONALE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Robin Tuytten; Filip Lemière; Walter Van Dongen; Eddy L Esmans; Erwin Witters; Wouter Herrebout; Benjamin Van Der Veken; Ed Dudley; Russell P Newton Journal: J Am Soc Mass Spectrom Date: 2005-08 Impact factor: 3.109
Authors: Dejan Nikolić; Tanja Gödecke; Shao-Nong Chen; Jerry White; David C Lankin; Guido F Pauli; Richard B van Breemen Journal: Fitoterapia Date: 2011-12-09 Impact factor: 2.882
Authors: Simon Beuck; Tobias Schwabe; Stefan Grimme; Nils Schlörer; Matthias Kamber; Wilhelm Schänzer; Mario Thevis Journal: J Am Soc Mass Spectrom Date: 2009-08-07 Impact factor: 3.109