Studies toward labeling cytisine with [11C]phosgene: rapid synthesis of a delta-lactam involving a new chemoselective lithiation-annulation method

J Org Chem. 2004 May 28;69(11):3787-93. doi: 10.1021/jo0498157.

Abstract

With the aim of the radiolabeling of cytisine, a potent agonist of nicotinic receptors, with [(11)C]phosgene, the rapid synthesis of a lactam model of our target has been studied. The key step of the delta-lactam formation is a new chemoselective lithiation-annulation method, under high dilution, of a suitable piperidinylcarbamoyl chloride. This precursor was obtained from (2-hydroxyethyl)piperidine in a linear synthetic sequence involving a Corey-Fuchs olefination of the corresponding aldehyde, followed by a selective reduction, using a diimide equivalent, of an iodoalkyne into a (Z)-iodopropene piperidine. This alkene served as main precursor to study the cyclization according to several procedures using phosgene as the required carbonylating reagent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Azocines / chemistry*
  • Carbon Radioisotopes
  • Isotope Labeling
  • Lactams / chemical synthesis*
  • Molecular Structure
  • Phosgene / chemistry*
  • Quinolizines / chemistry*

Substances

  • Alkaloids
  • Azocines
  • Carbon Radioisotopes
  • Lactams
  • Quinolizines
  • Phosgene
  • cytisine