Characterization of Novel Nucleoside Analogs by Electrospray Ionization Mass Spectra

Abstract

In this paper, we synthesized a novel nucleoside analog by coupling thymine with dimethyl dicarboxylate biphenyl (DDB). The structure of the target compound was determined using ¹H nuclear magnetic resonance (NMR) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). The fragmentation pathways were studied in detail through ESI-MS/MS. By comparing with unsubstituted nucleosides, such as AZT, MCI, d4T and DDI, it was found that the nucleoside analog coupled with DDB would not yield the daughter ions corresponding to the fragments of the nucleoside base and arabinofuranose analogs, but would lose a neutral molecule HF and DDB easily. However, the unsubstituted nucleosides could lightly yield the fragment ions of the nucleoside base and sugar ring. Hence, electrospray ionization mass spectrometry combined with tandem mass spectrometry provides a convenient method to recognize the substituted and unsubstituted nucleosides.

Keywords

nucleoside analog dimethyl dicarboxylate biphenyl (DDB)ESI-MS/MS

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References

Shaw

and Locarnini

, “Combination chemotherapy for hepatitis B virus-the path forward”, Drugs 60, 517 (2000).

T.W.

Pai

S.B.

and Chu

C.K.

, “Structure-Activity Relationships of 1-(2-Deoxy-2-fluoro-β-L-arabino-furanosyl)-pyrimidine Nucleosides as Anti-Hepatitis B Virus Agents”, J. Med. Chem. 39, 2835 (1996).

Zoulim

Aguesse

Borel

and Cheng

Y.C.

, “2′ Fluoro 5 methyl-β-L-arabinofuranosyluracil, a novel L-nucleoside analog, inhibits duck hepatitis B virus replication in primary hepatocytes and in vivo”, Antiviral Res. 30, A24 (1996).

Liguori

Napoli

and Sindona

, “Survey of the proton affinities of adenine, cytosine, thymine and uracil dideoxy-ribonucleosides, deoxyribonucleosides and ribonucleosides”, J. Mass. Spectrom. 35, 139 (2000).

Yen

T.Y.

and Charles

M.J.

, “Processes that Affect Electrospray Ionization Mass Spectrometry of Nucleobases and Nucleosides”, J. Am. Soc. Mass Spectrom. 7, 1106 (1996).

Hua

Y.S.

Wainhaus

S.B.

Yang

Y.N.

Shen

L.X.

Xiong

Y.S.

X.Y.

Zhang

F.G.

Bolton

J.L.

and Van Breemen

R.B.

, “Comparison of Negative and Positive Ion Electrospray Tandem Mass Spectrometry for the Liquid Chromatography Tandem Mass Spectrometry Analysis of Oxidized Deoxynucleosides”, J. Am. Soc. Mass Spectrom. 12, 80 (2000).

Wang

P.P.

Kotra

L.P.

Chu

C.K.

and Bartlett

M.G.

, “Structure Determination of 4-Azido-2-pyrimidinone Nucleoside Analogs Using Mass Spectrometry”, J. Mass. Spectrom. 34, 724 (1999).

Kamel

A.M.

and Munson

, “Collision-induced dissociation of purine antiviral agents: Mechanisms of ion formation using gas-phase hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry”, Eur. J. Mass Spectrom. 10, 239 (2004).

J.F.

Choi

Y.S.

and Chu

C.K.

, “A practical synthesis of L- FMALL from L-arabinose”, Nucleosides Nucleotides 18, 187 (1999).

10.

Guo

R.Y.

and Chang

J.B.

, “Syntheses Studies of 6,6′- Dimethoxy-4,5,4′,5′-dimethenedioxy-2,2′-dimethoxycarbonyl Biphenyl and Its Derivatives”, Chemical Journal of Chinese Universities 12, 2018 (2001).