Synthesis of carbon‐14 labelled spiro‐piperidyl‐rifamycins (LM 118) and rifabutin (LM 427)

Two syntheses of radiolabelled spiro‐piperidyl‐rifamycins are described. 1 . A five steps synthesis (Scheme 1) was performed to give 4‐deoxo‐3,4‐[2‐spiro‐(N‐[ 14 C]methyl‐4‐piperidyl)]‐(1H)‐imidazo‐(2,5‐dihydro)‐rifamycin S ([ 14 C]LM 118), in an overall radiochemical yield of ∼ 20%, 98% radiochemically pure and with a specific activity of 440 MBq/mmol (11.9 mCi/mmol) starting from [ 14 C]methyl iodide 1 . 2 . A three steps synthesis (Scheme 2) was performed to give 4‐deoxo‐3,4‐[2‐spiro‐(N‐2‐methyl[1‐ 14 C]propane‐4‐piperidyl)]‐(1H)‐imidazo‐(2,5‐dihydro)‐rifamycin S ([ 14 C] rifabutin) in an overall radiochemical yield of ∼38%, 97% radiochemically pure with a specific activity of 1.27 GBq/mmol (34.32 mCi/mmol). 1‐(2‐Methyl[1‐ 14 C]propanoyl)‐piperazin‐4‐one ethylene ketal was employed as starting material.