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Synthesis of labelled [ 15 N 3 ]‐6‐bromopurine, a useful precursor of 15 N‐labelled O 6 ‐alkylguanines, to be used as internal standards for quantitative GC‐MS analyses
Author(s) -
Lolli Marco,
Medana Claudio,
Romagnano Stefano,
Castoldi Fabio,
Pozzoli Stefano,
Vago Fulvio,
Fanelli Roberto,
Airoldi Luisa
Publication year - 1998
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199803)41:3<243::aid-jlcr73>3.0.co;2-h
Subject(s) - chemistry , formamide , hydrobromic acid , mass spectrometry , isotope dilution , yield (engineering) , bromide , bromine , cyanogen bromide , boron trifluoride , organic chemistry , chromatography , biochemistry , materials science , peptide sequence , metallurgy , gene , catalysis
[ 15 N 3 ]‐6‐Bromopurine was synthesized using readily available labelled starting materials. The 15 N‐labelled precursor guanidine, obtained from 15 NH 3 and cyanogen bromide, was condensed with ethyl cyanoacetate to give 4‐hydroxy‐[ 15 N 2 ]diaminopyrimidine. An additional 15 N isotope was incorporated by nitrosation with 15 N‐labelled sodium nitrite. After reduction to the corresponding triaminopyrimidine and condensation with formamide, [ 15 N 3 ]guanine was obtained in 96% yield and then converted to [ 15 N 3 ]‐6‐thioguanine by reacting it with phosphorus pentasulfide. [ 15 N 3 ]‐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. [ 15 N 3 ]‐6‐Bromopurine was the precursor for the subsequent synthesis of a series of O 6 ‐alkylguanines which can be used in isotope dilution mass spectrometry. © 1998 John Wiley & Sons, Ltd.