title: A high-yield route to synthesize the P-glycoprotein radioligand [11C]N-desmethyl-loperamide and its parent radioligand [11C]loperamide.
abstract: N-Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [(11)C]N-Desmethyl-loperamide and [(11)C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.
authors: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Min
authors: M
authors: Wang
authors: Mingzhang
authors: M
authors: Gao
authors: Qi-Huang
authors: QH
authors: Zheng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D008024:Ligands; D008139:Loperamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D052616:Solid Phase Extraction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; C419149:N-demethylloperamide; D008139:Loperamide
keywords: Automation; Brain imaging; P-glycoprotein (P-gp); Positron emission tomography (PET); [(11)C]Loperamide; [(11)C]N-Desmethyl-loperamide ([(11)C]dLop)