Synthesis of deuterium and C-13-labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O6-carboxymethyl-2′-deoxyguanosine

摘要

The adduct O6-carboxymethyl-2'-deoxyguanosine (O6CMdG) is of importance as it has been previously linked to high red meat diet in humans, and as yet, a liquid chromatography-mass spectrometry (LC-MS) method has not been developed due to lack of appropriate standards. The synthesis of the deuterated and C-13 analogues required the use of [2H2]- and [13C2]ethyl glycolate to label the carboxymethyl moiety of O6CMdG. [2H2]Ethyl glycolate was synthesised via acid hydrolysis of ethyl diazoacetate using deuterated solvents (59% yield), whilst [13C2]ethyl glycolate was synthesised from [13C2]glycine in a three-step procedure (35% yield). The labelled ethyl glycolates were then used to synthesise [2H2]- and [13C2]O6CMdG for future use as internal standards in the LC-MS analysis of biological samples. Copyright © 2011 John Wiley & Sons, Ltd.