Electrochemical Synthesis of a Sitagliptin Precursor.

Autor:	Oehl EK; Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany., Jirsch PT; Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany., Hammes J; Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany., Stenglein A; Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany., Méndez M; Sanofi R&D, Integrated Drug Discovery, Industriepark Höchst, Bldg. G838, 65926 Frankfurt am Main, Germany., Ruf S; Sanofi R&D, Integrated Drug Discovery, Industriepark Höchst, Bldg. G838, 65926 Frankfurt am Main, Germany., Waldvogel SR; Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany.; Karlsruher Institut für Technologie (KIT), Kaiserstraße 12, 76131 Karlsruhe, Germany.; Max-Planck-Institute for Chemical Energy Conversion, Stiftstraße 34-36, 45470 Mülheim an der Ruhr, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2024 Apr 24. Date of Electronic Publication: 2024 Apr 24.
DOI:	10.1021/acs.joc.4c00428
Abstrakt:	A novel synthesis of sitagliptin based on a redox-active ester derived from the chiral pool is reported. The key step is an electrochemical nickel-catalyzed sp 2 -sp 3 cross-coupling reaction using inexpensive nickel foam in an undivided cell. It was successfully applied to 21 examples in up to 88% yield. These sitagliptin-analogue precursors could potentially interact with the DPP4 enzyme. A full synthesis based on our new reaction pathway provided sitagliptin in an overall yield of 33%.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu