Catalytic asymmetric total synthesis of caprazamycin, an anti-tuberculosis antibiotic

• Project/Area Number: 23590037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: WATANABE Takumi 公益財団法人微生物化学研究会, 微生物化学研究所 有機合成研究部, 主席研究員 (80270544)
• Co-Investigator(Kenkyū-buntansha): SHIBASAKI Masakatsu (公財)微生物化学研究会, 微生物化学研 究所, 所長 (30112767)
• Co-Investigator(Renkei-kenkyūsha): ABE Hikaru (公財)微生物化学研究会, 微生物化学研 究所 有機合成研究部, 研究員 (10462269)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 全合成 / 天然有機化合物 / 触媒的不斉反応 / 抗結核剤 / 有機化学 / 抗結核薬

Research Abstract

A study on catalytic asymmetric total synthesis of caprazamycin, an anti-TB antibiotic, was conducted. The synthesis would be applied to structure-activity relationship study on the related compounds.
To install the correct stereochemistries embedded in the structure of caprazamycin, catalytic enantioselective nitroaldol- and thioamide aldol reactions that have been recently reported from the laboratory, newly developed catalytic asymmetric alcoholysis of 3-methylglutaric anhydride, and diastereoselective isocyanoacetate aldol reaction were utilized. During course of the study, catalytic asymmetric total synthesis of caprazol was accomplished.

Research Products

• [Journal Article] Catalytic asymmetric total synthesis of (+)-caprazol (2014)
  • Author(s): Gopinath, P., Wang, L., Abe, H., Ravi, G., Masuda, T., Watanabe, T., Shibasaki, M.
  • Journal Title: Org. Lett Volume: 16 Issue: 12 Pages: 3364-3367
  • DOI: 10.1021/ol501397b
  • Peer Reviewed
• [Journal Article] Studies on Catalytic Enantioselective Total Synthesis of Caprazamycin B : Construction of the Western Zone (2012)
  • Author(s): Gopinath, P., Watanabe, T. & Shibasaki M
  • Journal Title: J. Org. Chem. Volume: 77 Issue: 20 Pages: 9260-9267
  • DOI: 10.1021/jo301803h
  • Peer Reviewed
• [Journal Article] Catalytic eiantioselective desymmetrization of meso-glutaric anhydrides using a stable Ni_2-Schiff base catalys (2012)
  • Author(s): Gopinath, P., Watanabe, T., Shibasaki, M.
  • Journal Title: Org.Lett. Volume: 14 Issue: 5 Pages: 1358-1361
  • DOI: 10.1021/ol3002078
  • Peer Reviewed
• [Presentation] (2014)
  • Author(s): Gopinath Purushothaman,Ravi Gandamala,舛田岳史,渡辺匠,柴﨑正勝
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学・黒髪キャンパス(熊本市)
  • Year and Date: 2014-03-28
• [Presentation] Study on catalytic asymmetric total synthesis of caprazamycin B (2013)
  • Author(s): Takumi Watanabe, Purushothaman Gopinath, Takashi Masuda, Gandamala Ravi, Masakatsu Shibasaki
  • Organizer: 18th European symposium on organic chemistry
  • Place of Presentation: Palais du Pharo (Marseille,France)
  • Year and Date: 2013-07-08
• [Presentation] Studies on catalytic enantioselective total synthesis of caprazamycin B (2013)
  • Author(s): Gopinath Purushothaman,舛田岳史,渡辺匠,柴﨑正勝
  • Organizer: 第103回有機合成シンポジウム
  • Place of Presentation: 慶應義塾大学薬学部・芝共立キャンパス(東京都港区)
  • Year and Date: 2013-06-06
• [Presentation] Studies on catalytic enantioselective total synthesis of caprazamycin B (2013)
  • Author(s): Gopinath Purushothaman,舛田岳史,渡辺匠,柴﨑正勝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2013-03-30
• [Presentation] 抗結核活性を有する核酸系抗生物質caprazamycinBの触媒的不斉合成研究 (2012)
  • Author(s): プルショタマンゴピナス,渡辺匠,柴﨑正勝
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 2012-11-05
• [Presentation] Study on catalytic asymmetric total synthesis of caprazamycin B (2012)
  • Author(s): Takumi Watanabe, Purushothaman Gopinath, Takashi Masuda, Masakatsu Shibasaki
  • Organizer: 第6回武田科学振興財団薬科学シンポジウム
  • Place of Presentation: 武田薬品工業㈱研修所(吹田市)
  • Year and Date: 2012-09-13
• [Presentation] Study on catalytic asymmetric total synthesis of caprazamycin B (2012)
  • Author(s): T akumi Watanabe, Purushothaman Gopinath, Masakatsu Shibasaki
  • Organizer: 19th Intrnational conference on organic synthesis
  • Place of Presentation: Melbourne Convention & Exhibition Centre (Melbourne,Australia)
  • Year and Date: 2012-07-04
• [Presentation] Caprazamycin Bの触媒的不斉合成研究:1,2-syn-アミノアルコール部位の立体選択的構築 (2012)
  • Author(s): 渡辺匠、プルショタマンゴピナス、柴﨑正勝
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学・札幌キャンパス(札幌市)
  • Year and Date: 2012-03-30
• [Presentation] Progress towards the catalytic enantioselective total synthesis of caprazamycin B : Synthesis of the western zone (2012)
  • Author(s): Gopinath Purushothaman,渡辺匠,柴﨑正勝
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学・札幌キャンパス(札幌市)
  • Year and Date: 2012-03-29
• [Presentation] Caprazamycin Bの触媒的不斉合成研究：1,2-syn-アミノアルコール部位の立体選択的構築 (2012)
  • Author(s): 渡辺 匠、プルショタマン ゴピナス、柴崎正勝
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌（北海道大学札幌キャンパス）
• [Presentation] Progress towards the catalytic enantioselective total synthesis of caprazamycin B: Synthesis of the western zone. (2012)
  • Author(s): Gopinath Purushothaman, 渡辺 匠、柴崎正勝
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌（北海道大学札幌キャンパス）
• [Presentation] Study on Catalytic Asymmetric Total Synthesis of Caprazamycin B
  • Author(s): Takumi Watanabe, Purushothaman Gopinath, Takashi Masuda, Gandamala Ravi, Masakatsu Shibasaki
  • Organizer: 18th European Symposium on Organic Chemistry
  • Place of Presentation: Marseille (Palais du Pharo), France
• [Presentation] Caprazamycin Bの触媒的不斉全合成研究
  • Author(s): Gopinath Purushothaman， Ravi Gandamala，舛田岳史、渡辺 匠、柴﨑正勝
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本市（熊本大学・黒髪キャンパス）
• [Presentation] Study on catalytic asymmetric total synthesis of caprazamycin B
  • Author(s): Takumi Watanabe, Purushothaman Gopinath, Masakatsu Shibasaki
  • Organizer: 19th International Conference on Organic Synthesis
  • Place of Presentation: オーストラリア・メルボルン（Melbourne Convention & Exhibition Centre）
• [Presentation] Study on catalytic asymmetric total synthesis of caprazamycin B
  • Author(s): Takumi Watanabe, Purushothaman Gopinath, Takashi Masuda, Masakatsu Shibasaki
  • Organizer: 第6回武田科学技術振興財団薬科学シンポジウム
  • Place of Presentation: 大阪・吹田市（武田薬品工業（株）研修所）
• [Presentation] 医薬関連化合物の触媒的不斉合成研究
  • Author(s): 渡辺 匠
  • Organizer: 東京大学医科学研究所-微生物化学研究所 連携研究キックオフシンポジウム
  • Place of Presentation: 東京・東京大学医科学研究所
  • Invited
• [Presentation] 抗結核活性を有する核酸系抗生物質Caprazamycin Bの触媒的不斉合成研究
  • Author(s): プルショタマンゴピナス，渡辺匠，柴﨑正勝
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: 東京都江戸川区（タワーホール船堀）
• [Presentation] Progress towards the catalytic enantioselective total synthesis of Caprazamycin B: Synthesis of the western zone
  • Author(s): プルショタマンゴピナス，渡辺匠，柴﨑正勝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜（パシフィコ横浜）
• [Remarks]
  • URL: http://www.bikaken.or.jp/
• [Remarks] The Shibasaki Lab.
  • URL: http://www.bikaken.or.jp/research/group/shibasaki/shibasaki-lab/index.html