Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide
2,6-difluorobenzamides have been deeply investigated as antibacterial drugs in the last few decades. Several 3-substituted-2,6-difluorobenzamides have proved their ability to interfere with the bacterial cell division cycle by inhibiting the protein FtsZ, the key player of the whole process. Recentl...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/1422-8599/2023/1/M1559 |
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| author | Valentina Straniero Lorenzo Suigo Giulia Lodigiani Ermanno Valoti |
| author_facet | Valentina Straniero Lorenzo Suigo Giulia Lodigiani Ermanno Valoti |
| author_sort | Valentina Straniero |
| collection | DOAJ |
| description | 2,6-difluorobenzamides have been deeply investigated as antibacterial drugs in the last few decades. Several 3-substituted-2,6-difluorobenzamides have proved their ability to interfere with the bacterial cell division cycle by inhibiting the protein FtsZ, the key player of the whole process. Recently, we developed a novel family of 1,4-tetrahydronaphthodioxane benzamides, having an ethoxy linker, which reached sub-micromolar MICs towards Gram-positive <i>Staphylococcus aureus</i> and <i>Bacillus subtilis</i>. A further investigation of their mechanism of action should require the development of a fluorescent probe, and the consequent definition of a synthetic pathway for its obtainment. In the present work, we report the obtainment of an unexpected bicyclic side product, 6-fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide, coming from the substitution of one aromatic fluorine by the <i>in situ</i> formed alkoxy group, in the final opening of an epoxide intermediate. This side product was similarly achieved, in good yields, by opening the ring of both <i>erythro</i> and <i>threo</i> epoxides, and the two compounds were fully characterized using HRMS, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, HPLC and DSC. |
| first_indexed | 2024-03-11T06:08:42Z |
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| id | doaj.art-cbb57ad808914e6a9b41ff45e6e15e0f |
| institution | Directory Open Access Journal |
| issn | 1422-8599 |
| language | English |
| last_indexed | 2024-03-11T06:08:42Z |
| publishDate | 2023-01-01 |
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| series | Molbank |
| spelling | doaj.art-cbb57ad808914e6a9b41ff45e6e15e0f2023-11-17T12:49:25ZengMDPI AGMolbank1422-85992023-01-0120231M155910.3390/M1559Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamideValentina Straniero0Lorenzo Suigo1Giulia Lodigiani2Ermanno Valoti3Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milano, ItalyDipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milano, ItalyDipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milano, ItalyDipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli, 25, 20133 Milano, Italy2,6-difluorobenzamides have been deeply investigated as antibacterial drugs in the last few decades. Several 3-substituted-2,6-difluorobenzamides have proved their ability to interfere with the bacterial cell division cycle by inhibiting the protein FtsZ, the key player of the whole process. Recently, we developed a novel family of 1,4-tetrahydronaphthodioxane benzamides, having an ethoxy linker, which reached sub-micromolar MICs towards Gram-positive <i>Staphylococcus aureus</i> and <i>Bacillus subtilis</i>. A further investigation of their mechanism of action should require the development of a fluorescent probe, and the consequent definition of a synthetic pathway for its obtainment. In the present work, we report the obtainment of an unexpected bicyclic side product, 6-fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide, coming from the substitution of one aromatic fluorine by the <i>in situ</i> formed alkoxy group, in the final opening of an epoxide intermediate. This side product was similarly achieved, in good yields, by opening the ring of both <i>erythro</i> and <i>threo</i> epoxides, and the two compounds were fully characterized using HRMS, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, HPLC and DSC.https://www.mdpi.com/1422-8599/2023/1/M15592,6-difluorobenzamideFtsZ inhibitorsnucleophilic aromatic substitutionside product |
| spellingShingle | Valentina Straniero Lorenzo Suigo Giulia Lodigiani Ermanno Valoti Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide Molbank 2,6-difluorobenzamide FtsZ inhibitors nucleophilic aromatic substitution side product |
| title | Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide |
| title_full | Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide |
| title_fullStr | Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide |
| title_full_unstemmed | Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide |
| title_short | Obtainment of <i>Threo</i> and <i>Erythro</i> Isomers of the 6-Fluoro-3-(2,3,6,7,8,9-hexahydronaphtho[2,3-<i>b</i>][1,4]dioxin-2-yl)-2,3-dihydrobenzo[<i>b</i>][1,4]dioxine-5-carboxamide |
| title_sort | obtainment of i threo i and i erythro i isomers of the 6 fluoro 3 2 3 6 7 8 9 hexahydronaphtho 2 3 i b i 1 4 dioxin 2 yl 2 3 dihydrobenzo i b i 1 4 dioxine 5 carboxamide |
| topic | 2,6-difluorobenzamide FtsZ inhibitors nucleophilic aromatic substitution side product |
| url | https://www.mdpi.com/1422-8599/2023/1/M1559 |
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