The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates
A series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalys...
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2025-01-01
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| author | Zsuzsanna Szalai Anna Sára Kis Angéla Takács László Kőhidai Konstantin Karaghiosoff Mátyás Czugler László Drahos György Keglevich |
| author_facet | Zsuzsanna Szalai Anna Sára Kis Angéla Takács László Kőhidai Konstantin Karaghiosoff Mátyás Czugler László Drahos György Keglevich |
| author_sort | Zsuzsanna Szalai |
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| description | A series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalyst (1), on the surface of Al<sub>2</sub>O<sub>3</sub>/KF solid catalyst (2), or by a MW-assisted Na<sub>2</sub>CO<sub>3</sub>-catalyzed procedure (3). In most of the cases, our methods were more efficient and more robust than those applied in the literature. Two of the α-hydroxy-alkylphosphonates were subjected to single-crystal X-ray analysis, suggesting a dimeric and a chain supramolecular buildup in their respective crystals. Four α-hydroxy-alkylphosphonates and one α-hydroxy-ethylphosphine oxide were reacted with different acid chlorides to afford ten α-acyloxyphosphonates. Diethyl α-hydroxy-ethylphosphonate was transformed to the methanesulfonyloxy derivative that was useful in the Michaelis–Arbuzov reaction with triethyl phosphite and ethyl diphenylphosphinite to afford tetraethyl ethylidenebisphosphonate and diethyl α-(diphenylphosphinoyl)-ethylphosphonate, respectively. The α-hydroxyphosphonates and α-hydroxyphosphine oxides prepared were subjected to bioactivity studies, and the compounds tested exhibited limited cytotoxic effects on U266 cells with modest reductions in viability at a concentration of 100 μM. |
| format | Article |
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| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-059cd8497fbb4884980898b0142e5bc32025-01-24T13:44:00ZengMDPI AGMolecules1420-30492025-01-0130242810.3390/molecules30020428The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-AlkylphosphonatesZsuzsanna Szalai0Anna Sára Kis1Angéla Takács2László Kőhidai3Konstantin Karaghiosoff4Mátyás Czugler5László Drahos6György Keglevich7Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, HungaryDepartment of Genetics, Cell-and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Genetics, Cell-and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, GermanyDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, HungaryMS Proteomics Research Group, Research Centre for Natural Sciences, 1117 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, HungaryA series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalyst (1), on the surface of Al<sub>2</sub>O<sub>3</sub>/KF solid catalyst (2), or by a MW-assisted Na<sub>2</sub>CO<sub>3</sub>-catalyzed procedure (3). In most of the cases, our methods were more efficient and more robust than those applied in the literature. Two of the α-hydroxy-alkylphosphonates were subjected to single-crystal X-ray analysis, suggesting a dimeric and a chain supramolecular buildup in their respective crystals. Four α-hydroxy-alkylphosphonates and one α-hydroxy-ethylphosphine oxide were reacted with different acid chlorides to afford ten α-acyloxyphosphonates. Diethyl α-hydroxy-ethylphosphonate was transformed to the methanesulfonyloxy derivative that was useful in the Michaelis–Arbuzov reaction with triethyl phosphite and ethyl diphenylphosphinite to afford tetraethyl ethylidenebisphosphonate and diethyl α-(diphenylphosphinoyl)-ethylphosphonate, respectively. The α-hydroxyphosphonates and α-hydroxyphosphine oxides prepared were subjected to bioactivity studies, and the compounds tested exhibited limited cytotoxic effects on U266 cells with modest reductions in viability at a concentration of 100 μM.https://www.mdpi.com/1420-3049/30/2/428α-hydroxy-alkylphosphonatesPudovik reactionacylationsulfonylationArbuzov reactionX-ray structure |
| spellingShingle | Zsuzsanna Szalai Anna Sára Kis Angéla Takács László Kőhidai Konstantin Karaghiosoff Mátyás Czugler László Drahos György Keglevich The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates Molecules α-hydroxy-alkylphosphonates Pudovik reaction acylation sulfonylation Arbuzov reaction X-ray structure |
| title | The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates |
| title_full | The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates |
| title_fullStr | The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates |
| title_full_unstemmed | The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates |
| title_short | The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates |
| title_sort | synthesis crystal structure modification and cytotoxic activity of α hydroxy alkylphosphonates |
| topic | α-hydroxy-alkylphosphonates Pudovik reaction acylation sulfonylation Arbuzov reaction X-ray structure |
| url | https://www.mdpi.com/1420-3049/30/2/428 |
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