Biomimetic Synthesis of Drug Metabolites in Batch and Continuous-Flow Reactors.

Autor: Fődi T; Compound Profiling Laboratory, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary.; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary., Ignácz G; Compound Profiling Laboratory, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary.; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary., Decsi B; Compound Profiling Laboratory, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary.; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary., Béni Z; Spectroscopic Research Department, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary., Túrós GI; Medicinal Chemistry Laboratory II, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary., Kupai J; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary., Weiser DB; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary.; Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Budafoki út 8, 1111, Budapest, Hungary., Greiner I; Research Directorate, Chemical Works, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary., Huszthy P; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary., Balogh GT; Compound Profiling Laboratory, Gedeon Richter Plc, Gyömrői út 19-21, 1103, Budapest, Hungary.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2018 Jul 02; Vol. 24 (37), pp. 9385-9392. Date of Electronic Publication: 2018 Jun 10.
DOI: 10.1002/chem.201800892
Abstrakt: A medium-throughput screening (MTS) of biomimetic drug metabolite synthesis is developed by using an iron porphyrin catalyst. The microplate method, in combination with HPLC-MS analysis, was shown to be a useful tool for process development and parameter optimization in the production of targeted metabolites and/or oxidation products of forty-three different drug substances. In the case of the biomimetic oxidation of amiodarone, the high quantity and purity of the isolated products enabled detailed HRMS and NMR spectroscopic studies. In addition to identification of known metabolites, several new oxidation products of the drug that was studied were characterized. Fast degradation and poor recovery of the catalyst under batch conditions was overcome by immobilization of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin iron(III) chloride (FeTSPP) on the surface of 3-aminopropyl-functionalized silica by electrostatic interaction. The supported catalyst was successfully applied in a packed-bed reactor under continuous-flow reaction conditions for the large-scale synthesis of amiodarone metabolites.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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