¹¹C‐Labeling: Intracyclic Incorporation of Carbon‐11 into Heterocycles

Abstract

Labeling of heterocycles with carbon‐11 is generally performed through peripheral functionalizations and more scarcely inside heterocyclic core. Such less common approach usually requires preliminary multi‐step synthesis of reactive species. Herein, a cyclization reaction by direct use of cyclotron‐produced [11C]CO2 is described to obtain various heterocycles intracyclically labeled in only 10 minutes.

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

“…[ 6 - 11 C]­Theophylline was synthesized first by Liger et al . in 2019 . This is a one-step reaction, where zinc chloride and 1 , 3 -bis­( 2 , 6 -diisopropylphenyl)­imidazol- 2 -ylidene (IPr) were added to the vial, followed by a solution of amine in diglyme (Figure ).…”

“…[ 11 C]­CO 2 was then released within the vial cooled at 0 °C, and the reaction vial was heated at 150 °C for 10 min. [ 6 - 11 C]­Theophylline was obtained with a RCY of 14–18% from the end of [ 11 C]­CO 2 trapping within the vial . Unfortunately, [ 6 - 11 C]­theophylline has not been evaluated to the best of our knowledge.…”

“…Scopolamine is initially delivered to the brain in a perfusion-directed pattern, where a significant brain parenchymal tracer uptake was observed. After 30−60 min, activity is lost from the cerebellum, thalamus preferen- 153 This is a one-step reaction, where zinc chloride and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) were added to the vial, followed by a solution of amine in diglyme (Figure 45). Diphenylsilane was added last, and the vial was sealed.…”

“…[6-11 C]Theophylline was obtained with a RCY of 14−18% from the end of [ 11 C]CO 2 trapping within the vial. 153 Unfortunately, [6-11 C]theophylline has not been evaluated to the best of our knowledge.…”

“…Besides the compounds described below (Table 11), other natural exogenous compounds, less common, have been labeled with carbon-11. Among these, [ 11 C]cinnamic acid 802 (oil of cinnamon), [ 11 C]1,3-diphenylurea 803,804 (a cytokinin found in coconut milk), [ 11 C]benzothiazole 153 (food additive), [ 11 C]benzaldehyde 805 (food additive), [ 11 C]octanal 805 (citrus oil), and [ 11 C]heptanoic acid 531 (additive in cigarettes). However, these compounds have been described only in one or two studies and not evaluated in vivo.…”