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  Crystallographic evidence for unintended benzisothiazolinone 1-oxide formation from benzothiazinones through oxidation

Eckhardt, T., Goddard, R., Lehmann, C., Richter, A., Sahile, H. A., Liu, R., et al. (2020). Crystallographic evidence for unintended benzisothiazolinone 1-oxide formation from benzothiazinones through oxidation. Acta Crystallographica, Section C: Crystal Structure Communications, 76(9), 907-913. doi:10.1107/S2053229620010931.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-45ED-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-45EE-0
Genre: Journal Article

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 Creators:
Eckhardt, Tamira1, Author
Goddard, Richard2, Author              
Lehmann, Christoph1, Author
Richter, Adrian1, Author
Sahile, Henok Asfaw3, Author
Liu, Rui4, Author
Tiwari, Rohit4, Author
Oliver, Allen G.4, Author
Miller, Marvin J.4, Author
Seidel, Rüdiger W.1, Author
Imming, Peter1, Author
Affiliations:
1Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale),Germany, ou_persistent22              
2Service Department Lehmann (EMR), Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1445625              
3Department of Medicine and Department of Microbiology and Immunology, University of British Columbia, Vancouver,British Columbia, V6T 1Z3, Canada, ou_persistent22              
4Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556, USA, ou_persistent22              

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Free keywords: benzothiazinone; BTZ043; benzisothiazolinone; ring contraction; crystal structure; antimycobacterial activity
 Abstract: 1,3-Benzothiazin-4-ones (BTZs) are a promising new class of drugs with activity against Mycobacterium tuberculosis, which have already reached clinical trials. A product obtained in low yield upon treatment of 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzothiazin-4-one with 3-chloroperbenzoic acid, in analogy to a literature report describing the formation of sulfoxide and sulfone derived from BTZ043 [Tiwari et al.(2015). ACS Med. Chem. Lett. 6, 128–133], is a ring-contracted benzisothiazolinone (BIT) 1-oxide, namely, 7-nitro-2-(piperidine-1-carbonyl)-5-(trifluoromethyl)benzo[d]isothiazol-3(2H)-one 1-oxide, C14H12F3N3O5S, as revealed by X-ray crystallography. Single-crystal X-ray analysis of the oxidation product originally assigned as BTZ043 sulfone provides clear evidence that the structure of the purported BTZ043 sulfone is likewise the corresponding BIT 1-oxide, namely, 2-[(S)-2-methyl-1,4-dioxa-8-azaspiro[4.5]-decane-8-carbonyl]-7-nitro-5-(trifluoromethyl)benzo[d]isothiazol-3(2H)-one1-oxide, C17H16F3N3O7S. A possible mechanism for the ring contraction affording the BIT 1-oxides instead of the anticipated constitutionally isomeric BTZ sulfones and antimycobacterial activities thereof are discussed.

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Language(s): eng - English
 Dates: 2020-06-292020-08-092020-09-01
 Publication Status: Published online
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1107/S2053229620010931
 Degree: -

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Title: Acta Crystallographica, Section C: Crystal Structure Communications
  Other : Acta Crystallogr., Sect. C: Cryst. Struct. Commun.
Source Genre: Journal
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Publ. Info: Copenhagen, Denmark : Published for International Union of Crystallography by Munksgaard
Pages: - Volume / Issue: 76 (9) Sequence Number: - Start / End Page: 907 - 913 Identifier: ISSN: 0108-2701
CoNE: https://pure.mpg.de/cone/journals/resource/110987085479123