Nature Publishing Group Acta Medica Okayama 2045-2322 7 1 2017 Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality 8239 EN Christopher J. Vavrick Graduate School of Environmental and Life Science, Okayama University Chiaki Muto Graduate School of Environmental and Life Science, Okayama University Tomohisa Hasunuma Graduate School of Science, Technology and Innovation, Kobe University Yoshinobu Kimura Graduate School of Environmental and Life Science, Okayama University Michihiro Araki Graduate School of Science, Technology and Innovation, Kobe University Yan Wu CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences George F. Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences Hiroshi Ohrui Yokohama College of Pharmacy Minoru Izumi Graduate School of Environmental and Life Science, Okayama University Hiromasa Kiyota Graduate School of Environmental and Life Science, Okayama University The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 7 1 2017 Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality 8239 EN Christopher J. Vavricka Graduate School of Environmental and Life Science, Okayama University Chiaki Muto Graduate School of Environmental and Life Science, Okayama University Tomohisa Hasunuma Graduate School of Science, Technology and Innovation, Kobe University Yoshinobu Kimura Graduate School of Environmental and Life Science, Okayama University Michihiro Araki Graduate School of Science, Technology and Innovation, Kobe University Yan Wu CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences George F. Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences Hiroshi Ohrui Yokohama College of Pharmacy Minoru Izumi Graduate School of Environmental and Life Science, Okayama University Hiromasa Kiyota Graduate School of Environmental and Life Science, Okayama University The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors. No potential conflict of interest relevant to this article was reported.