title: Synthesis of ¹⁸F-labelled β-lactams by using the Kinugasa reaction.
abstract: Owing to their broad spectrum of biological activities and low toxicity, β-lactams are attractive lead structures for the design of novel molecular probes. However, the synthesis of positron emission tomography (PET)-isotope-labelled β-lactams has not yet been reported. Herein, we describe the simple preparation of radiofluorinated β-lactams by using the fast Kinugasa reaction between (18)F-labelled nitrone [(18)F]-1 and alkynes of different reactivity. Additionally, (18)F-labelled fused β-lactams were obtained through the reaction of a cyclic nitrone 7 with radiofluorinated alkynes [(18)F]-6 a,b. Radiochemical yields of the Kinugasa reaction products could be significantly increased by the use of different Cu(I) ligands, which additionally allowed a reduction in the amount of precursor and/or reaction time. Model radiofluorinated β-lactam-peptide and protein conjugates ([(18)F]-10 and (18)F-labelled BSA conjugate) were efficiently obtained in high yield under mild conditions (aq. MeCN, ambient temperature) within a short reaction time, demonstrating the suitability of the developed method for radiolabelling of sensitive molecules such as biopolymers.
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Strasse 62, 50937 Cologne (Germany), Fax: (+49) 221-478-86851; Max Planck Institute of Neurological Research, Gleueler Strasse 50, 50931 Cologne (Germany); Clinic of Nuclear Medicine, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen (Germany).
authors.forename: Boris D
authors.initials: BD
authors.lastname: Zlatopolskiy
authors.forename: Philipp
authors.initials: P
authors.lastname: Krapf
authors.forename: Raphael
authors.initials: R
authors.lastname: Richarz
authors.forename: Holm
authors.initials: H
authors.lastname: Frauendorf
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D002417:Cattle; D057930:Click Chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D009589:Nitrogen Oxides / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000480:Alkynes; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D009589:Nitrogen Oxides; D019275:Radiopharmaceuticals; D047090:beta-Lactams; C015388:nitrones; D012710:Serum Albumin, Bovine
keywords: click chemistry; imaging agents; isotopic labelling; radiopharmaceuticals; β-lactams