Abstract
We have been working on finding new bioactive microbial metabolites at the Kitasato Institute. Their microbial natural products have a variety of unique and complex skeletones with many chiral centers and functional groups, and biological activities. We also have been working on synthetic study of them, which is effective and concise convergent approach, designed to afford easy access to both the natural products and a variety of analogs to clarify the structure-activity relationships.We have succeeded in the efficient total syntheses of bioactive microbial metabolites; pyripyropene (1), arisugacin (2), lactacystin (3), macrosphelide (4), and madindoline (5), and the construction of indoline spiroaminal moiety of neoxaline (6). We also have succeeded in creating better analogs of pyripyropene (1) and lactacystin (3).Furthermore, we have also been working on synthetic study of macrolides which have a variety of biological activities and also clarifying the mode of action in order to develop novel medicines. We have succeeded in creating novel macrolides, a motilide (EM574) and an anti-inflammatory agent (EM905).
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