Identification of Amino Acid Phosphorodiamidates of Antiviral Nucleosides Using Electrospray Ionisation Tandem Mass Spectrometry

• Published in: European journal of mass spectrometry (Chichester, England) England), 2011-01, Vol.17 (2), p.187-195
• Main Authors: Cui, Juntao, Gao, Xiang, Fan, Aiting, Zhang, Shuangyan, Liu, Yan, Xu, Pengxiang, Zhao, Yufen
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Anti-HIV Agents - chemistry; Phosphorus Compounds - chemistry; Spectrometry, Mass, Electrospray Ionization - methods; Stavudine - chemistry; Tandem Mass Spectrometry - methods; Zidovudine - chemistry
• ISSN: 1469-0667; 1751-6838
• DOI: 10.1255/ejms.1111

Several amino acid phosphorodiamidate derivatives of d4T as anti-HIV prodrugs were synthesised and investigated using electrospray ionisation multistage tandem mass spectrometry (ESI-MSn). A novel methyl group migration in the gas phase was observed in ESI-MS2 of the sodium adducts of amino acid methyl ester of phosphorodiamidates of 2′,3′-didehydro-2′,3′-dideox y thymidine (d4T). The proposed structures of the rearrangement ions were confirmed by high-resolution tandem mass spectrometry. A possible mechanism involving the pentacoordinate phosphoric–carboxylic phosphate anhydride was proposed, in which a seven-membered ring intermediate was formed by coordination with the metal ion between the phosphoryl group and carbonyl oxygen atom. Thus, the intrinsic properties of phosphoryl group might be the key factors responsible for this migration.