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 γ position rather than the α or β position of the anthracene moiety by an electrophilic substitution mechanism.

Graphical AbstractProposed rearrangement mechanism in ESI-MS/MS.Figure optionsDownload full-size imageDownload high-quality image (121 K)Download as PowerPoint slide