The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates
Zsuzsanna Szalai,
Anna Sára Kis,
Angéla Takács,
László Kőhidai,
Konstantin Karaghiosoff,
Mátyás Czugler,
László Drahos,
György Keglevich
Affiliations
Zsuzsanna Szalai
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, Hungary
Anna Sára Kis
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, Hungary
Angéla Takács
Department of Genetics, Cell-and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary
László Kőhidai
Department of Genetics, Cell-and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary
Konstantin Karaghiosoff
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, Germany
Mátyás Czugler
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, Hungary
László Drahos
MS Proteomics Research Group, Research Centre for Natural Sciences, 1117 Budapest, Hungary
György Keglevich
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, Hungary
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 Al2O3/KF solid catalyst (2), or by a MW-assisted Na2CO3-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.
