Use of optically active cyclic diethyl sulfamidate 2-phosphonates as chiral synthons for the synthesis of β-substituted α-amino phosphonates |
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| Institution: | 1. University of Greifswald, Institute of Biochemistry, Felix-Hausdorff Str. 4, 17487 Greifswald, Germany;2. Biocatalysis and Organic Synthesis Group, Federal University of Rio de Janeiro (UFRJ), Institute of Chemistry, Rio de Janeiro 21941-909, RJ, Brazil;1. Ataturk University, Faculty of Sciences, Department of Chemistry, Erzurum, Turkey;2. Erzurum Technical University, Faculty of Science, Department of Basic Sciences, Erzurum, Turkey;1. Universidade Federal Do ABC, Centro de Ciências Naturais e Humanas, Av. Dos Estados 5001, Santo André, SP, 09210-580, Brazil;2. Universidade de São Paulo, Instituto de Química, Av. Prof. Lineu Prestes 748, São Paulo, SP, 05508-900, Brazil;1. School of Pharmacy, Federal University of Rio de Janeiro – UFRJ, 21941-902 Rio de Janeiro, RJ, Brazil;2. Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Federal University of Rio de Janeiro – UFRJ, Rio de Janeiro, Brazil;3. Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro – UFRJ, 21941-902 Rio de Janeiro, Brazil;4. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Brazil;5. Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143, USA;6. Laboratory for Macromolecules, DIMAV, Brazilian National Institute of Metrology, Quality and Technology – INMETRO, Av. N. Sa. das Graças, 50, Xerém, Duque de Caxias-RJ 25250-020, Rio de Janeiro, Brazil;7. National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil |
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| Abstract: | Optically active protected sulfamidate 2-phosphonates have been synthesized from either (R)- or (S)-N-benzyl-2-phosphonoserine for use as chiral synthons. These sulfamidates have been shown to undergo nucleophilic substitution with select nucleophiles, to afford following N-sulfate removal, the β-substituted α-amino-2-phosphonates. N-Sulfate removal was accomplished using boron trifluoride etherate in the presence of either n-propylthiol or N-hydroxysuccinimide allowing retention of the diethylphosphonate ester groups. Replacement of the unpleasant smelling n-propylthiol with N-hydroxysuccinimide provides higher yields of the desired products. Synthesis of β-S-substituted analogues required the use of cesium carbonate as a base. The sulfamidates described have excellent stability and have been demonstrated, using chiral HPLC, to be greater than 97% enantiomerically pure. |
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