Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/85984
Title: New insight into dearomatization and decarbonylation of antitubercular 4H-Benzo[e][1,3]thiazinones : stable 5H- and 7H-Benzo[e][1,3]thiazines
Author(s): Richter, AdrianLook up in the Integrated Authority File of the German National Library
Seidel, Rüdiger W.Look up in the Integrated Authority File of the German National Library
Graf, Jürgen
Goddard, Richard W.Look up in the Integrated Authority File of the German National Library
Lehmann, Christoph
Schlegel, Tom
Khater, Nour
Imming, PeterLook up in the Integrated Authority File of the German National Library
Issue Date: 2022
Type: Article
Language: English
Abstract: 8-Nitro-4H-benzo[e][1,3]thiazinones (BTZs) are potent in vitro antimycobacterial agents. New chemical transformations, viz. dearomatization and decarbonylation, of two BTZs and their influence on the compounds’ antimycobacterial properties are described. Reactions of 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one and the clinical drug candidate BTZ043 with the Grignard reagent CH3MgBr afford the corresponding dearomatized stable 4,5-dimethyl-5H- and 4,7-dimethyl-7H-benzo[e][1,3]thiazines. These methine compounds are structurally characterized by X-ray crystallography for the first time. Reduction of the BTZ carbonyl group, leading to the corresponding markedly non-planar 4H-benzo[e][1,3]thiazine systems, is achieved using the reducing agent (CH3)2S ⋅ BH3. Double methylation with dearomatization and decarbonylation renders the two BTZs studied inactive against Mycobacterium tuberculosis and Mycobacterium smegmatis, as proven by in vitro growth inhibition assays.
URI: https://opendata.uni-halle.de//handle/1981185920/87937
http://dx.doi.org/10.25673/85984
Open Access: Open access publication
License: (CC BY-NC-ND 4.0) Creative Commons Attribution NonCommercial NoDerivatives 4.0(CC BY-NC-ND 4.0) Creative Commons Attribution NonCommercial NoDerivatives 4.0
Sponsor/Funder: Publikationsfonds MLU
Journal Title: ChemMedChem
Publisher: Wiley-VCH
Publisher Place: Weinheim [u.a.]
Volume: 17
Issue: 6
Original Publication: 10.1002/cmdc.202200021
Appears in Collections:Open Access Publikationen der MLU