Syntheses of [2-13C] and [1,2-13C] labelled α-ketoglutaric acid

The syntheses of α-keto[2-13C]glutaric acid and α-keto[1,2-13C]glutaric acid were each achieved from commercial 13CH3I in 5 steps. 13CH3NO2, prepared in situ from 13CH3I and AgNO2, was treated with magnesium methyl carbonate, followed by acidified methanol to give O2N13CH2CO2CH3. Michael addition to methyl acrylate, followed by in situ nitronate formation and ozonolysis gave the dimethyl ester of α-keto [2-13C]glutaric acid, which was deprotected with hydrochloric acid. O2N13CH213CO2CH3 was prepared from 13CH3NO2 by reaction with aqueous KOH, followed by treatment with acidified methanol, and was converted to 1,2-13C-α-ketoglutaric acid in a similar fashion to that used for mono-labelled material. (author)