Friedel-Crafts dealkylation reaction mediated by a stereoselective proton transfer in the fragmentation of protonated cyclic indolyl α-amino esters.
Chiral cyclic indolyl α-amino esters are valuable substructures of peptides and peptidomimetics. Systematically exploring the fragmentation behavior of the protonated cyclic indolyl α-amino esters by a combination of high-resolution high-energy collisional dissociation mass spectrometry, hydrogen-deuterium exchange experiments and density functional theory (DFT) calculations is useful for further understanding their intrinsic properties and the fragmentation mechanisms of peptidomimetics constructed with them.



All high-resolution high-energy collisional dissociation tandem mass spectrometry experiments were carried out using electrospray ionization hybrid Quadrupole-Orbitrap mass spectrometry in positive ion mode. Only the labile hydrogens were exchanged with deuterium in hydrogen-deuterium exchange experiments. Theoretical calculations were carried out by the DFT method at the B3LYP level with the 6-311G(d,p) basis set in the Gaussian 03 package of programs.



In the fragmentation of protonated cyclic indolyl α-amino esters, when the two labile hydrogens on the N(8) position are successively transferred to the C(3) and C(4) positions, a Friedel-Crafts dealkylation reaction takes place spontaneously, with concomitant formation of an ion-neutral complex of [cyclic N-sulfonyl ketimino esters/protonated indoles]. Direct separation of this complex formed the protonated indoles, while a stereoselective proton transfer between the two components in the complex gave rise to protonated cyclic N-sulfonyl ketimino esters, which coincided with the hydrogen-deuterium experiments.



Using H/D exchange experiments combined with theoretical calculations, a Friedel-Crafts dealkylation reaction mediated by a stereoselective proton transfer in the [cyclic N-sulfonyl ketimino esters/protonated indoles] complex was proposed for the fragmentation of protonated cyclic indolyl α-amino esters in high-energy collisional dissociation tandem mass spectrometry for the first time. Copyright © 2016 John Wiley & Sons, Ltd.
Research Center of Analysis and Measurement, Zhejiang University of Technology, 18 Chaowang Rd, Hangzhou, Zhejiang, 310014, P.R., China.
Xiaoji
X
Cao
College of Chemical Engineering, Zhejiang University of Technologys, 18 Chaowang Rd, Hangzhou, Zhejiang, 310014, P.R., China.
Ye
Y
Wang
College of Chemical Engineering, Zhejiang University of Technologys, 18 Chaowang Rd, Hangzhou, Zhejiang, 310014, P.R., China.
Yawen
Y
Mo
College of Chemical Engineering, Zhejiang University of Technologys, 18 Chaowang Rd, Hangzhou, Zhejiang, 310014, P.R., China.
Liang
L
Wu
Research Center of Analysis and Measurement, Zhejiang University of Technology, 18 Chaowang Rd, Hangzhou, Zhejiang, 310014, P.R., China.
Weimin
W
Mo
D003640:Dealkylation; D004952:Esters; D008958:Models, Molecular; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization
D004952:Esters; D011522:Protons