Recent development of two chitinase inhibitors, Argifin and Argadin, produced by soil microorganisms

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  • HIROSE Tomoyasu
    The Kitasato Institute, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University
  • SUNAZUKA Toshiaki
    The Kitasato Institute, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University
  • ŌMURA Satoshi
    The Kitasato Institute, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University

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Chitin, the second most abundant polysaccharide in nature, occurs in fungi, some algae and many invertebrates, including insects. Thus, chitin synthesis and degradation could represent specific targets for fungicides and insecticides. Chitinases hydrolyze chitin into oligomers of N-acetyl-D-glucosamine at key points in the life cycles of organisms, consequently, chitinase inhibitors have become subject of increasing interest. This review covers the development of two chitinase inhibitors of natural origin, Argifin and Argadin, isolated from the cultured broth of microorganisms in our laboratory. In particular, the practical total synthesis of these natural products, the synthesis of lead compounds via computer-aided rational molecular design, and discovery methods that generate only highly-active compounds using a kinetic target(chitinase)-guided synthesis approach (termed in situ click chemistry) are described.<br><br>(Contributed by Satoshi ŌMURA, M.J.A.)

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