A high-yield route to synthesize the P-glycoprotein radioligand [ 11C]N-desmethyl-loperamide and its parent radioligand [ 11C]loperamide

Min Wang, Mingzhang Gao, Qi-Huang Zheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

Original languageEnglish
Pages (from-to)5259-5263
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number19
DOIs
StatePublished - Oct 1 2013

Fingerprint

Loperamide
P-Glycoprotein
Amides
Methylation
Solid Phase Extraction
High Pressure Liquid Chromatography
N-demethylloperamide
4-(4'-chlorophenyl)-4-piperidinol

Keywords

  • [C]N-Desmethyl-loperamide ([C]dLop) [ C]Loperamide
  • Automation
  • Brain imaging
  • P-glycoprotein (P-gp)
  • Positron emission tomography (PET)

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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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. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30{\%} and 10-15{\%} radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.",
keywords = "[C]N-Desmethyl-loperamide ([C]dLop) [ C]Loperamide, Automation, Brain imaging, P-glycoprotein (P-gp), Positron emission tomography (PET)",
author = "Min Wang and Mingzhang Gao and Qi-Huang Zheng",
year = "2013",
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doi = "10.1016/j.bmcl.2013.08.024",
language = "English",
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T1 - A high-yield route to synthesize the P-glycoprotein radioligand [ 11C]N-desmethyl-loperamide and its parent radioligand [ 11C]loperamide

AU - Wang, Min

AU - Gao, Mingzhang

AU - Zheng, Qi-Huang

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

AB - 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. [11C]N-Desmethyl-loperamide and [ 11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

KW - [C]N-Desmethyl-loperamide ([C]dLop) [ C]Loperamide

KW - Automation

KW - Brain imaging

KW - P-glycoprotein (P-gp)

KW - Positron emission tomography (PET)

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