Routine synthesis of N-[11C-methyl]scopolamine by phosphite mediated reductive methylation with [11C]formaldehyde.
A synthesis of [11C]scopolamine capable of clinical delivery of this agent in high specific activity is described. The precursor [11C]formaldehyde was produced by catalytic oxidation of [11C]CH3OH over metallic silver and was used to N-11C-methylate norscopolamine using aqueous neutral potassium phosphite as the reducing agent. The labeling reaction was complete after 5 min at 75-80 degrees C and the [11C]scopolamine (99% radiochemical purity) was isolated by preparative HPLC. Total synthesis time is less than 45 min. Decay corrected radiochemical yields from [11C]CO2 are presently 20-43%.
Mulholland
G K
GK
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0552.
Jewett
D M
DM
Toorongian
S A
SA
D002250:Carbon Radioisotopes; D005557:Formaldehyde; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000138:chemical synthesis*; D017905:Phosphites; D010757:Phosphorous Acids; D017680:Potassium Compounds; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives / Q000138:chemical synthesis*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D010276:Parasympatholytics; D017905:Phosphites; D010757:Phosphorous Acids; D017680:Potassium Compounds; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C056591:potassium phosphite; D005557:Formaldehyde; D019832:N-Methylscopolamine