A novel rearrangement of fluorescent human thymidylate synthase inhibitor analogues in ESI tandem mass spectrometry.
Cu(I) catalyzed alkyne-azide cycloaddition reaction was employed to synthesize a series of anthracene-based human thymidylate synthase (hTS) inhibitor analogues. The triazolo-anthracene derivatives were characterized by ESI-MS/MS and a novel rearrangement reaction in ESI-MS/MS was observed. The mechanism is proposed whereby the protonated triazolo-anthracene derivative forms a carbocation, and then the carbocation electrophilically attacks an anthracene moiety resulting in formation of a rearrangement ion. Moreover, the carbocation prefers to attack the gamma position rather than the alpha or beta position of the anthracene moiety by an electrophilic substitution mechanism.
Chen
Yi
Y
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA.
Le Droumaguet
Céline
C
Li
Kai
K
Cotham
William E
WE
Lee
Norman
N
Walla
Mike
M
Wang
Qian
Q
D000873:Anthracenes / Q000032:analysis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000873:Anthracenes; D005456:Fluorescent Dyes; D013940:Thymidylate Synthase; C034020:anthracene