Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The

• targeted cancer therapy development. Keywords: 1,4-benzothiazine; 1,3-benzothiazole; 1H-pyrrole-2,3-diones; nitrogen heterocycle; sulfur heterocycle; Introduction Pyrrolo[2,1-b][1,3]benzothiazole (PBTA) is an angularly fused sulfur and nitrogen-containing heterocyclic scaffold. Its derivatives are

• , recently, we have reported a new class of FPDs, aroylpyrrolobenzothiazinetriones (APBTTs) 1 (Figure 2) [37][38], whose structural features allowed us to assume a possibility of the development of a new approach to PBTAs via a nucleophile-induced ring contraction in the 1,4-benzothiazine moiety of compounds

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• synthesis and utilization of derivatives of 4H-benzo[b][1,4]thiazine-3-carboxylic acid. These benzothiazine compounds were assembled via the coupling of aminothiols and bromopyruvates. Oxidative dimerization of these starting materials was also observed and the corresponding benzothiazine dimers were

• isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished. Keywords: amino acid; benzothiazine; oxidative dimerization; peptide coupling; stereoselective

• hydrogenation; Introduction Heterocyclic compounds with a benzothiazine moiety are attractive building blocks in medicinal chemistry. Benzo-1,4-thiazine derivatives possess a wide range of biological and pharmacological properties, such as anticancer and antitumor, antioxidant, antimicrobial, antibacterial

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• /addition/nucleophilic substitution reactions. Keywords: aza-Wittig reaction; 3,4-dihydroquinazoline; 4H-3,1-benzothiazine; nucleophilic substitution; Passerini reaction; Staudinger reaction; Introduction The chemistry of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines is of constant interest owing to

• protein cleaving enzyme 1 (BACE-1) inhibitive [6], and cholinesterase enzyme inhibitive activities [7]. The 3,4-dihydroquinazoline skeleton also exists in some natural products such as vasicine and vasicoline [8]. Some 4H-3,1-benzothiazine derivatives have also received attention due to their good

• biological activities, including anticancer [9], neuroprotective [10], antiproliferative and antifungal activities [11]. Due to the significant bioactive properties of the 3,4-dihydroquinazoline and 4H-3,1-benzothiazine moieties, many preparation procedures have appeared in the literature for the synthesis

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• )-27-6. Enantioselective fluorinations of typical enolates were then performed (Scheme 63). The (R)-27-6 reagent gave up to 79% yield and 88% enantiomeric excess in the case of 2-benzyl-α-tetralone. 1-28. (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-benzothiazine 1,1-dioxides and spiro-type analogues In

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• ; 1,4-benzothiazine; cyclocondensation; diversity-oriented synthesis; furan-2,3-dione; Introduction Enaminones fused to the 1,4-benzoxazine-2-one I or quinoxaline-2(1H)-one II moiety (Figure 1) represent an intensively investigated class of enamines. Undying interest in these compounds is due to the

New simple synthesis of ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thiones: Direct formation from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles

• Qiuping Ding,
• Yuqing Lin,
• Guangni Ding,
• Fumin Liao,
• Xiaoyan Sang and
• Yi-Yuan Peng

Beilstein J. Org. Chem. 2013, 9, 460–466, doi:10.3762/bjoc.9.49

• and efficient method to construct ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thione derivatives has been developed from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles under mild conditions, without the need for a metal catalyst. The newly developed method

• tolerates a wide range of substrates in moderate to excellent yields. Moreover, this method is advantageous over previous ones for the easy synthesis of reactants. Keywords: 4H-3,1-benzothiazine-2-thione; carbon disulfide; (E)-3-(2-aminoaryl)acrylate; (E)-3-(2-aminoaryl)acrylonitrile; Michael addition

• ; Introduction Molecules containing the 4H-3,1-benzothiazine moiety have received considerable interest from the chemical and medicinal community due to their promising biological activity [1][2][3][4] and the applications in recording and photographic materials [5][6][7][8]. A number of efficient approaches for

On the functionalization of benzo[e][2,1]thiazine

• Kirill Popov,
• Tatyana Volovnenko and
• Julian Volovenko

Beilstein J. Org. Chem. 2009, 5, No. 42, doi:10.3762/bjoc.5.42

• derivatives of benzothiazine exhibit biological activity that ranges from antipsychotic [1] to anti-inflammatory [2], depending on the substituents present [3][4]. However, medicinal applications are limited as a consequence of side effects [5][6]. Much research has been carried out over the last 20 years

• with a view to improving benzothiazine-based drugs and to avoid the adverse effects [6][7]. In previous work [8][9] we reported the synthesis of some novel benzothiazines, in particular benzo[e][2,1]thiazine derivatives, the β-chloroaldehydes 1 and β-chloronitriles 2 (Figure 1); their chemistry was

• shown to be quite versatile. Compounds 1 and 2 both contain 1,3-dielectrophilic fragments, which are C-4 carbon atoms of the benzothiazine ring and carbonyl group or nitrile function, respectively. Thus, further investigation of aldehydes 1 and nitriles 2 should provide new benzo[e][2,1]thiazine