新型1,2,3-三唑基甲基-2H-1,4-苯并噻嗪-3(4H)-酮衍生物的合成及其抗菌活性

Synthesis and antibacterial activity of new 1,2,3-triazolylmethyl-2H-1,4-benzothiazin-3(4H)-one derivatives.

作者信息

Ellouz Mohamed, Sebbar Nada Kheira, Fichtali Ismail, Ouzidan Younes, Mennane Zakaria, Charof Reda, Mague Joel T, Urrutigoïty Martine, Essassi El Mokhtar

机构信息

Laboratoire de Chimie Organique Hétérocyclique, Centre de Recherche des Sciences des Médicaments, Pôle de Compétences Pharmacochimie, Faculté des Sciences, Mohammed V University in Rabat, Av. Ibn Battouta, BP 1014, Rabat, Morocco.

Laboratoire de Chimie Bioorganique Appliquée, Faculté des Sciences, Université Ibn Zohr, Agadir, Morocco.

出版信息

Chem Cent J. 2018 Nov 29;12(1):123. doi: 10.1186/s13065-018-0494-2.

BACKGROUND

A novel series of 1,2,3-triazole derivatives containing 1,4-benzothiazin-3-one ring (7a-9a, 7b-9b), (10a-12a, 10b-12b) and (13-15) were synthesized by 1,3-dipolar cycloaddition reactions of azides α-D-galactopyranoside azide F, 2,3,4,6-tetra-O-acetyl-(D)-glucopyranosyl azide G and methyl-N-benzoyl-α-azidoglycinate H with compounds 4-6.

FINDINGS

Initially, the reactions were conducted under thermal conditions in ethanol. The reaction leads, each time, to the formation of two regioisomers: (Schemes 2, 3) with yields of 17 to 21% for 1,5-disubstituted 1,2,3-triazole-regioisomers (7b-12b) and yields ranging from 61 to 65% for the 1,4-disubstituted regioisomers (7a-12a). In order to report an unequivocal synthesis of the 1,4-regioisomers and confirm the structures of the two regioisomers obtained in thermal conditions (Huisgen reactions), the method click chemistry (Copper-Catalyzed Azide-Alkyne Cycloaddition) has been used.

CONCLUSIONS

The newly synthesized compounds using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram positive and Gram negative microbial strains. Among the compounds tested, the compound 8a showed excellent antibacterial activities against PA ATCC and Acin ESBL (MIC = 31.2 μg/ml).

背景

通过叠氮化物α-D-吡喃半乳糖苷叠氮化物F、2,3,4,6-四-O-乙酰基-(D)-吡喃葡萄糖基叠氮化物G和甲基-N-苯甲酰基-α-叠氮基甘氨酸酯H与化合物4-6的1,3-偶极环加成反应，合成了一系列含1,4-苯并噻嗪-3-酮环的新型1,2,3-三唑衍生物（7a-9a、7b-9b）、（10a-12a、10b-12b）和（13-15）。

研究结果

最初，反应在乙醇中热条件下进行。每次反应都会生成两种区域异构体：（方案2、3）1,5-二取代的1,2,3-三唑区域异构体（7b-12b）的产率为17%至21%，1,4-二取代区域异构体（7a-12a）的产率为61%至65%。为了明确报道1,4-区域异构体的合成并确认在热条件下（惠斯根反应）获得的两种区域异构体的结构，采用了点击化学方法（铜催化的叠氮化物-炔烃环加成）。