{"id":350,"date":"2021-08-26T14:54:14","date_gmt":"2021-08-26T05:54:14","guid":{"rendered":"http:\/\/media-creations.org\/ogurilab\/?page_id=350"},"modified":"2025-01-23T08:13:38","modified_gmt":"2025-01-23T08:13:38","slug":"research-2","status":"publish","type":"page","link":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/en\/research-2\/","title":{"rendered":"Research"},"content":{"rendered":"\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe loading=\"lazy\" title=\"\u5927\u6817 \u535a\u6bc5\uff08\u6771\u5927\u30fb\u6559\u6388\uff09\u300c\u5929\u7136\u7269\u5408\u6210\u306e\u65b0\u5c55\u958b\u3092\u76ee\u6307\u3057\u3066\u300d\uff08\u7b2c\u5341\u56deV\u30b7\u30f3\u30dd\uff09\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/u2FWJhsa5kI?start=1363&#038;feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe>\n<\/div><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-group is-content-justification-center is-nowrap is-layout-flex wp-container-core-group-is-layout-94bc23d7 wp-block-group-is-layout-flex\">\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"355\" src=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-1024x355.png\" alt=\"\" class=\"wp-image-1308\" style=\"width:202px;height:70px\" srcset=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-1024x355.png 1024w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-300x104.png 300w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-768x266.png 768w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-1536x532.png 1536w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35-150x52.png 150w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/38be182c709a9743374fa708e3d2ee35.png 1640w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><a href=\"https:\/\/www.s.u-tokyo.ac.jp\/en\/rigakuru\/research\/vFRkjeIB\/\">RIGAKU-RU &#8220;Creating Molecules that Could Change the World&#8221; <\/a>Sept. 9, 2022<\/p>\n<\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Modular assembly line synthesis of skeletally diverse molecules<\/strong> (ref. 1\u20135)<\/h3>\n\n\n\n<p>Organic synthesis that diversifies the three-dimensional structures through generation of diverse molecular scaffolds is becoming more important as an innovative technology toward the creation of functional substances based on regulation at atomic\/molecular levels.&nbsp; We are exploring synthetic approaches that not only mimic biosynthetic processes generating a wide variety of secondary metabolites but also redesign the modular divergent assembly lines.&nbsp; Our synthetic campaigns aim to develop a concise and versatile synthetic process allowing systematic generation of \u201cscaffold variations\u201d through programmable manipulations of a common multipotent intermediate. These investigations are formulating advanced synthetic strategies to gain expeditious and cost-effective access to the natural product-relevant chemical space with diversification of skeletal, stereochemical, and functional group properties.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"621\" src=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-1024x621.png\" alt=\"\" class=\"wp-image-2186\" style=\"width:728px;height:auto\" srcset=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-1024x621.png 1024w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-300x182.png 300w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-768x466.png 768w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-1536x932.png 1536w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-2048x1243.png 2048w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/Indoledivergent241224-150x91.png 150w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n<h3 class=\"wp-block-heading\"><strong>Redesigning Biosynthetic Process: Chemo-enzymatic Hybrid Synthesis<\/strong> (ref. 6\u20137)<\/h3>\n\n\n\n<p>Plants and microorganisms have evolved the enzymatic machinery to efficiently biosynthesize natural products under physiological conditions.&nbsp; Our approach focuses on the merger of the in vitro engineered biosynthesis and the precise organic synthesis to facilitate the generation of natural product-based complex molecules towards drug discovery and chemical genetic investigations.&nbsp; By streamlining enzymatic reactions and chemical manipulations, we developed a chemoenzymatic hybrid process that allowed very rapid and operationally simple access to the densely functionalized pentacyclic alkaloidal skeleton within a single day from two simple synthetic substrates.&nbsp; The judicious choice of the designer substrates for the enzyme SfmC allowed divergent total syntheses of saframycins and jorunnamycins in just 4\u20135 pot, which could be a versatile platform for the collective synthesis of natural products and their variants.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"744\" src=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-1024x744.png\" alt=\"\" class=\"wp-image-590\" style=\"width:604px;height:auto\" srcset=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-1024x744.png 1024w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-300x218.png 300w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-768x558.png 768w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-1536x1116.png 1536w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-2048x1488.png 2048w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/210928-Research-THIQ-2-150x109.png 150w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n<h3 class=\"wp-block-heading\"><strong>Chemical biology utilizing covalent ligands<\/strong> <meta charset=\"utf-8\"><\/meta> (ref. 8\u20139)<\/h3>\n\n\n\n<p>Artemisinin and its derivatives, the active ingredients of traditional Chinese medicine, have revolutionized the malaria chemotherapy.&nbsp; Reductive cleavage of the peroxide bridge by intracellular heme iron generates carbon radical species responsible for the formation of a covalent linkage with biomolecules and the enhancement of oxidative stress.&nbsp; The 6-aza-artemisinins were designed by replacing a stereogenic carbon center at C6 with a nitrogen, which allowed both structural modification of the hitherto unexplored C-ring and concise de novo synthesis.&nbsp; By exploiting the natural products variants, we will streamline concise synthesis, screening, and identification of the covalent complexes composed of the synthetic ligands and biomacromolecules.&nbsp; These efforts are expected to facilitate the development of lead candidates for the treatment of infectious diseases and cancers.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"551\" src=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-1024x551.png\" alt=\"\" class=\"wp-image-2208\" style=\"width:628px;height:auto\" srcset=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-1024x551.png 1024w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-300x161.png 300w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-768x413.png 768w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-1536x826.png 1536w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-2048x1102.png 2048w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/9fdcafb727327d7b5eaa9b34e3945351-150x81.png 150w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n<h3 class=\"wp-block-heading\"><strong>Supramolecular assemblies of natural product-based scaffolds<\/strong> (ref. 10)<\/h3>\n\n\n\n<p>In efforts to generate self-assembling nanostructures, we paid attention to the precise molecular recognition capabilities of natural products with dense arrays of sp3 stereogenic centers and various functional groups.&nbsp; The C2-symmetric alkaloidal skeleton has been demonstrated to be a versatile chiral scaffold for supramolecular chemistry, capable of generating configurational variations of the sp3 stereogenic centers and thereby customizing the conformational flexibility, chiroptical property and self-assembling behavior.&nbsp; We are developing the natural product-based versatile scaffolds that project multiple functional units with systematic diversification of the spatial arrangements.&nbsp; Supramolecular assemblies of the synthetic mid-sized molecules will be investigated to improve their sensing functions.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"236\" src=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-1024x236.png\" alt=\"\" class=\"wp-image-2207\" srcset=\"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-1024x236.png 1024w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-300x69.png 300w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-768x177.png 768w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-1536x355.png 1536w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-2048x473.png 2048w, https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp\/wp-content\/uploads\/e32204a5d9340091fc4cd70af807ed7a-150x35.png 150w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n<h3 class=\"wp-block-heading\">References<\/h3>\n\n\n\n<ol>\n<li>Biogenetically inspired synthesis and skeletal diversification of indole alkaloids. H. Mizoguchi, H. Oikawa, H. Oguri.<em> Nat. Chem.<\/em> <strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2014<\/strong>, <em>6<\/em>, 57\u201364.<\/li>\n<li>Zn(OTf)<sub>2<\/sub>-mediated annulations of <em>N<\/em>-propargylated tetrahydrocarbolines: divergent synthesis of four distinct alkaloidal scaffolds. S. Yorimoto, A. Tsubouchi, H. Mizoguchi, H. Oikawa, Y. Tsunekawa, T. Ichino, S. Maeda, H. Oguri. <em>Chem. <\/em><em> Sci. <\/em><strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2019<\/strong><em>, 10, <\/em>5686\u20135698<em>.<\/em><\/li>\n<li>Synthesis of a Halicyclamine-type Macrocyclic Scaffold via Biomimetic Transannular Cyclization. T. Wayama, H. Oguri. <i style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">Org. Lett.<\/i> <strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2023<\/strong><span style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">, 25, 3596\u20133601.<\/span><\/li>\n<li>Synthetic Modulation of an Unstable Dehydrosecodine-type Intermediate and Its Encapsulation into a Confined Cavity Enable Its X-ray Crystallographic Observation. G. Tay, T. Wayama, H. Takezawa, S. Yoshida, S. Sato, M. Fujita, H. Oguri. <span class=\"s1\" style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\"><i>Angew. Chem. Int. Ed<\/i><\/span><span style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">. <\/span><span class=\"s1\" style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\"><b>2023<\/b><\/span><span style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">, 62, e202305122.<\/span><\/li>\n<li>Direct photochemical intramolecular [4 + 2] cycloadditions of dehydrosecodine-type substrates for the synthesis of the iboga-type scaffold and divergent [2 + 2] cycloadditions employing micro-flow system. G. Tay, S. Nishimura, H. Oguri <em>Chem. Sci.<\/em> <strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2024<\/strong><span style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">, 15, 15599\u2013<\/span><span style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">15609 (Edge Article).<\/span><\/li>\n<li>Chemo-enzymatic Total Syntheses of Jorunnamycin A, Saframycin A, and <em>N<\/em>-Fmoc Saframycin Y3. R. Tanifuji, K. Koketsu, M. Takakura, R. Asano, A. Minami, H. Oikawa, H. Oguri. <em>J. Am. Chem. Soc. <\/em><strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2018<\/strong>, <em>140<\/em>, 10705\u201310709.<\/li>\n<li>Chemo-enzymatic total syntheses of bis-tetrahydroisoquinoline alkaloids and systematic exploration of the substrate scope of SfmC. R. Tanifuji, N. Haraguchi, H. Oguri, <em>Tetrahedron Chem. <\/em><strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2022<\/strong><em><strong>,<\/strong><\/em>\u00a0<em>1<\/em>, 100010.<\/li>\n<li>Rapid and Systematic Exploration of Chemical Space Relevant to Artemisinins: Anti-malarial Activities of Skeletally Diversified Tetracyclic Peroxides and 6-Aza-artemisinins. <i>J. Org. Chem<\/i><span style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">. <\/span><span class=\"s1\" style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\"><b>2020<\/b><\/span><span style=\"font-size: revert; color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">, 85, 9694\u20139712.<\/span><\/li>\n<li>Synthesis and Structural Diversification of Artemisinins Towards the Generation of Potent Anti-malarial Agents H. Oguri. <span class=\"s1\"><i>Chem. Lett<\/i><\/span>. <strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2021<\/strong>, 50, 924\u2013937 (highlighted review).<\/li>\n<li>Rapid Synthesis of Chiral Figure-Eight Macrocycles Using a Preorganized Natural Product-Based Scaffold. T. Honda, D. Ogata, M. Tsurui, S. Yoshida, S. Sato, T. Muraoka,. Y. Kitagawa, Y. Hasegawa, J. Yuasa, H. Oguri <em>Angew. Chem. Int. Ed. <\/em><strong style=\"color: initial; font-family: -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, Oxygen-Sans, Ubuntu, Cantarell, 'Helvetica Neue', sans-serif;\">2024<\/strong>, e202318548.<\/li>\n<\/ol>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>RIGAKU-RU &#8220;Creating Molecules that Could Change the World&#8221; Sept. 9, 2022 Modular assembly line syn [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"_locale":"en_US","_original_post":"http:\/\/media-creations.org\/ogurilab\/?page_id=9","vkexunit_cta_each_option":"","footnotes":""},"class_list":["post-350","page","type-page","status-publish","hentry","en-US"],"acf":[],"_links":{"self":[{"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/pages\/350","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/comments?post=350"}],"version-history":[{"count":39,"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/pages\/350\/revisions"}],"predecessor-version":[{"id":2250,"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/pages\/350\/revisions\/2250"}],"wp:attachment":[{"href":"https:\/\/natural.chem.s.u-tokyo.ac.jp\/wp-json\/wp\/v2\/media?parent=350"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}