Publicação
Design and synthesis of swainsonine analogs from 2,4-benzilidene D-erythrose, assisted by theoretical studies
| Resumo: | The development of novel molecules with biological activity is always a trend topic in chemistry, as are the development of new synthetic pathways for their synthesis. In this work functionalized hehaxydropyrroloquinolines-2,3-diol were synthetized by aminocyclization of substituted tetrahydroquinolines. Tetrahydroquinolines were obtained in two steps from protected D-erythrose and anilines: 1) condensation of aldehyde and anilines, 2) inverse electron-demand Diels-Alder cycloaddition with N-vinylpyrrolidone in presence Lewis acid as catalyst, (Povarov’s reaction). The effect of differently m-substituted anilines was evaluated in terms of regio-selectivity of reactions. Different catalysts were also tested. In parallel to the synthetic work, were conducted theoretical studies using diverse molecular modelling techniques, namely: protein structure prediction of human Golgi α- mannosidase II and lysosomal α-mannosidase; docking studies of novel compounds against these target enzymes, and molecular dynamics simulations of inhibitor-enzyme complexes. From a synthetic point of view, four new compounds were synthetized with moderate yields. Significant progresses have been achieved within this work to give a picture of the methodological possibilities used. Computational results did not include the four compounds obtained in the experiment section, otherwise suggest two new hits for synthesis and biological tests. It must be recognized that further studies combining experimental, theoretical and biological studies will led to a solution to the problem in test with a full comprehension of the systems under study. |
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| Autores principais: | Drogalin, Artem |
| Assunto: | Asymmetric synthesis Docking studies D-erythrose Hehaxydropyrroloquinoline Molecular dynamic simulations Dinâmica molecular D-eritrose Estudos de docking Hehaxidropirroloquinolina Síntese assimétrica Ciências Naturais::Outras Ciências Naturais |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | The development of novel molecules with biological activity is always a trend topic in chemistry, as are the development of new synthetic pathways for their synthesis. In this work functionalized hehaxydropyrroloquinolines-2,3-diol were synthetized by aminocyclization of substituted tetrahydroquinolines. Tetrahydroquinolines were obtained in two steps from protected D-erythrose and anilines: 1) condensation of aldehyde and anilines, 2) inverse electron-demand Diels-Alder cycloaddition with N-vinylpyrrolidone in presence Lewis acid as catalyst, (Povarov’s reaction). The effect of differently m-substituted anilines was evaluated in terms of regio-selectivity of reactions. Different catalysts were also tested. In parallel to the synthetic work, were conducted theoretical studies using diverse molecular modelling techniques, namely: protein structure prediction of human Golgi α- mannosidase II and lysosomal α-mannosidase; docking studies of novel compounds against these target enzymes, and molecular dynamics simulations of inhibitor-enzyme complexes. From a synthetic point of view, four new compounds were synthetized with moderate yields. Significant progresses have been achieved within this work to give a picture of the methodological possibilities used. Computational results did not include the four compounds obtained in the experiment section, otherwise suggest two new hits for synthesis and biological tests. It must be recognized that further studies combining experimental, theoretical and biological studies will led to a solution to the problem in test with a full comprehension of the systems under study. |
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