Synthesis of labelled [15N3]‐6‐bromopurine, a useful precursor of 15N‐labelled O6‐alkylguanines, to be used as internal standards for quantitative GC‐MS analyses

Autor: Lolli, Marco, Medana, Claudio, Romagnano, Stefano, Castoldi, Fabio, Pozzoli, Stefano, Vago, Fulvio, Fanelli, Roberto, Airoldi, Luisa
Zdroj: Journal of Labelled Compounds and Radiopharmaceuticals; March 1998, Vol. 41 Issue: 3 p243-252, 10p
Abstrakt: [15N3]‐6‐Bromopurine was synthesized using readily available labelled starting materials. The 15N‐labelled precursor guanidine, obtained from 15NH3and cyanogen bromide, was condensed with ethyl cyanoacetate to give 4‐hydroxy‐[15N2]diaminopyrimidine. An additional 15N isotope was incorporated by nitrosation with 15N‐labelled sodium nitrite. After reduction to the corresponding triaminopyrimidine and condensation with formamide, [15N3]guanine was obtained in 96% yield and then converted to [15N3]‐6‐thioguanine by reacting it with phosphorus pentasulfide. [15N3]‐6‐Thioguanine was readily converted to the corresponding bromopurine using bromine in the presence of methanolic hydrobromic acid. The final product was characterized by mass spectrometry. [15N3]‐6‐Bromopurine was the precursor for the subsequent synthesis of a series of O6‐alkylguanines which can be used in isotope dilution mass spectrometry. © 1998 John Wiley & Sons, Ltd.
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