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Inhibition of the sodium-glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [ 18 F]canagliflozin was developed via a Cu-mediated 18 F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [ 18 F]canagliflozin with a yield of 0.5-3% ( n = 4) and a purity of >95%. Autoradiography showed [ 18 F]canagliflozin binding in human kidney sections containing SGLT2. Since [ 18 F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.

Background: [ 18 F]MC225 is a radiotracer for imaging P-glycoprotein (P-gp) function at the blood-brain barrier. The P-gp function can be altered due to different factors, for instance, decreased P-gp function has been described in patients with Alzheimer's or Parkinson's Disease. The current applied radiosynthesis of [ 18 F]MC225 involves 2 steps, including the distillation of the [ 18 F] fluoroethylbromide intermediate. To develop a more robust synthetic procedure, it is of interest to produce the radiotracer via a 1-step synthesis. The present study describes a new synthetic approach to produce [ 18 F]MC225 via direct 18 F-fluorination. Moreover, we also provide the appropriate conditions for the automation of the synthesis. A mesylate precursor was synthesized via a multi-step synthetic route and used for the radiolabeling. The nucleophilic substitution of the mesylate group by [ 18 F] Fluoride was automated in two different synthesis modules: IBA Synthera and Eckert and Ziegler PharmTracer (E&Z)., Results: The mesylate precursor was synthesized in 7 steps starting with 5-hydroxy-1-tetralone (commercially available) in practical yields. The stability of the precursor was improved via mesylate salt formation method. The radiolabeling was done by adding the mesylate precursor dissolved in DMF to the dried [ 18 F]KF/K 2.2.2 complex and heating at 140 °C for 30 min. Quality control by UPLC confirmed the production of [ 18 F]MC225 with a molar activity (A m ) higher than 100 GBq/micromole. The synthesis time in Synthera was 106 min and the product was obtained with a radiochemical purity higher than 95% and RCY of 6.5%, while the production in E&Z lasted 120 min and the product had a lower radiochemical purity (91%) and RCY (3.8%)., Conclusions: [ 18 F]MC225 was successfully produced via a 1-step reaction. The procedure is suitable for automation using commercially available synthesis modules. The automation of the radiosynthesis in the Synthera module allows the production of the [ 18 F]MC225 by a reliable and simple method., (© 2021. The Author(s).)

A highly active organocatalytic system based on N-heterocyclic carbenes has been designed for the formylation of N-H bonds in a large variety of nitrogen molecules and heterocycles, using two chemical wastes: CO(2) and polymethylhydrosiloxane (PMHS).

A new family of lanthanide ionic complexes derived from chiral, substituted (R)-binaphthylamine ligands, [Li(thf)(4)][Ln{(R)-C(20)H(12)(NR)(2)}(2)] (Ln=Yb, Sm, Nd, or Lu), has been synthesized and characterized by X-ray crystal structure analyses. All complexes have been tested as new catalysts for the hydroamination/cyclization of 1-(aminomethyl)-1-allylcyclohexane. Ytterbium complexes proved to be both the most active and the most enantioselective, and the use of the complex [Li(thf)(4)][Yb{(R)-C(20)H(12)(NC(3)H(7))(2)}(2)], bearing isopropyl radicals on the nitrogen atoms, allowed the formation of the corresponding spiropyrrolidine in high yield with up to 70 % ee.