Study of asymmetric total synthesis of nakadomarin A

• Project/Area Number: 21790012
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: INAGAKI Fuyuhiko Kanazawa University, 薬学系, 助教 (80506816)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 有機化学 / ナカドマリンA / Pauson-Khand 反応 / 天然物合成 / アレン / Pauson-Khand / Pauson-Khand反応

Research Abstract

We completed the total synthesis of (+)-nakadomarin in a highly stereoselectve manner from the commercially available L-pyroglutamic acid. The most significant point of this synthesis involves the intramolecular Pauson-Khand reaction between the alkyne and N-protected-dihydropyrrole functionalities, which enabled us to construct the diazatricyclo[6.4.0.0^<1,5>]dodcadienone product. This reaction was also useful for the short-step synthesis of (±)-meloscine. In addition, we succeeded to extend the application of the rhodium catalyzed Pauson-Khand type reaction of allenenes for the construction of bicyclo[4.3.0] skeletons containing quaternary carbon at the ring juncture. This method provided a new procedure for the construction of the tricyclo[6.4.0.0^<1,5>]dodecenone framework in a satisfactory yield.

Research Products

• [Journal Article] Org. (2011)
  • Author(s): Inagaki, F., Itoh, N., Hayashi, Y.,Matsui, Y., Mukai, C.,Beilstein J.
  • Journal Title: Chem. 7 Pages: 404-409
  • Peer Reviewed
• [Journal Article] Org. (2011)
  • Author(s): Hayashi, Y., Inagaki, F., Mukai, C.
  • Journal Title: Lett 13 Pages: 1778-1780
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Inagaki, F., Kitagaki, S., Mukai, C.
  • Journal Title: Synlett Pages: 594-614
  • Peer Reviewed
• [Journal Article] Rh(1)-catalyzed Intramolecular [2+2+1] Cycloaddition of Allenenes : Construction of Ricyclo[4.3.0]nonenones with an Angular Methyl Group and Tricyclo[6.4.0.0^<1.5>]dodecenone (2011)
  • Author(s): F.Inagaki
  • Journal Title: Beilstein J.Org.Chem. Volume: 7 Pages: 404-409
  • Peer Reviewed
• [Journal Article] Total Synthesis of (±)-Meloscine (2011)
  • Author(s): Y.Hayashi
  • Journal Title: Org.Lett. Volume: 13 Pages: 1778-1780
  • Peer Reviewed
• [Journal Article] Construction of Diverse Ring Systems Based on Allene-Multiple Bond Cycloaddition (2011)
  • Author(s): F.Inagaki
  • Journal Title: Synlett Pages: 594-614
  • Peer Reviewed
• [Journal Article] Chem. (2010)
  • Author(s): Kawamura, T., Inagaki, F., Narita, S.,Takahashi, Y., Hirata, S., Kitagaki, S.,Mukai, C.
  • Journal Title: Eur.J. 16 Pages: 5173-5183
  • Peer Reviewed
• [Journal Article] Org. (2010)
  • Author(s): Inagaki, F., Kinebuchi, M., Miyakoshi,N., Mukai, C.
  • Journal Title: Lett 12 Pages: 1800-1803
  • Peer Reviewed
• [Journal Article] Angew.Chem. (2010)
  • Author(s): Inagaki, F., Sugikubo, K., Miyashita,Y., Mukai, C.
  • Journal Title: Int.Ed. 49 Pages: 2206-2210
  • Peer Reviewed
• [Journal Article] Rhodium(I)-Catalyzed Intramolecular Carbonylative [2+2+1]Cycloadditions and Cycloisomerizations of Bis(sulfonylallene)s (2010)
  • Author(s): T.Kawamura
  • Journal Title: Chem.Eur.J. Volume: 16 Pages: 5173-5183
  • Peer Reviewed
• [Journal Article] Formal Synthesis of (+)-Nakadomarin A (2010)
  • Author(s): Inagaki, F.
  • Journal Title: Org.Lett. (in press)
  • Peer Reviewed
• [Journal Article] Rhodium(I)-Catalyzed Intramolecular [5+2] Cycloaddition Reactions of Alkynes and Allenylc yclopropanes : Construction of Bicyclo[5.4.0]undecatrienes and Bicyclo[5.4.0]dodecatrienes (2010)
  • Author(s): Inagaki, F
  • Journal Title: Angew.Chem.Int.Ed. 49 Pages: 2206-2210
  • Peer Reviewed
• [Journal Article] J.Org. (2009)
  • Author(s): Aburano, D., Inagaki, F., Tomonaga, S.,Mukai, C.
  • Journal Title: Chem 74 Pages: 5590-5594
  • Peer Reviewed
• [Journal Article] J.Org. (2009)
  • Author(s): Inagaki, F., Mizutani, M., Kuroda, N.,Mukai, C.
  • Journal Title: Chem. 74 Pages: 6402-6405
  • Peer Reviewed
• [Journal Article] Synthesis of a Core Carbon Framework of Cyanosporasides A and B (2009)
  • Author(s): Aburano, D
  • Journal Title: J.Org.Chem. 74 Pages: 5590-5594
  • Peer Reviewed
• [Journal Article] Generation of N-(tert-Butoxycarbonyl)indole-2, 3-quinodimethane and Its [4+2]-Type Cycloaddition (2009)
  • Author(s): Inagaki, F
  • Journal Title: J.Org.Chem. 74 Pages: 6402-6405
  • Peer Reviewed
• [Presentation] ニトロンとスルホニルアレンとの位置選択的分子内[3+2]環化付加反応 (2011)
  • Author(s): 稲垣冬彦, 小林春美, 向智里
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 東日本大震災のため誌上開催
  • Year and Date: 2011-03-31
• [Presentation] Diels-Alder反応を利用したビシクロ[m.4.0]骨格(m=6,7)の効率的構築法の開発 (2011)
  • Author(s): 稲垣冬彦, 高橋康仁, 向智里
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 東日本大震災のため誌上開催
  • Year and Date: 2011-03-31
• [Presentation] (±)-Scandineの合成研究 (2011)
  • Author(s): 林佑次郎
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: (東日本大震災のため誌上開催)
  • Year and Date: 2011-03-29
• [Presentation] 多重結合の特性を活用した分子内環化反応とその応用 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 北陸大学(石川県)
  • Year and Date: 2010-11-21
• [Presentation] 多置換型ビスアレンを用いたRh(I)触媒分子内Pauson-Khand型反応の開発 (2010)
  • Author(s): 稲垣冬彦, 高橋康仁, 小川久美子, 成田集, 向智里
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 北陸大学(石川県)
  • Year and Date: 2010-11-21
• [Presentation] 多重結合の特性な活用した分子内環化反応とその応用 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 北陸大学アネックスファーム(石川県)(招待講演)
  • Year and Date: 2010-11-21
• [Presentation] アレンを基盤とする中員環含有双環性骨格の新規構築 (2010)
  • Author(s): 稲垣冬彦, 川村行正, 杉窪克哉, 成田集,宮下祐輔, 平田修一, 北垣伸治, 向智里
  • Organizer: 第36回反応と合成の進歩シンポジウム-ライフサイエンスを志向した理論、反応および合成-
  • Place of Presentation: ウインクあいち(愛知県)
  • Year and Date: 2010-11-01
• [Presentation] アレンを基盤とする中員環含有双環性骨格の新規構築 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 反応と合成の進歩シンポジウム
  • Place of Presentation: ウインクあいち(愛知県)
  • Year and Date: 2010-11-01
• [Presentation] Goniomitineの不斉全合成研究 (2010)
  • Author(s): 水谷仁弥, 稲垣冬彦, 向智里
  • Organizer: 第40回複素環化学討論会
  • Place of Presentation: 仙台市民会館(宮城県)
  • Year and Date: 2010-10-15
• [Presentation] Pauson-Khand反応を活用した効率的な多環状天然物の合成:(±)-meloscine 及び(+)-nakadomarin A の全合成 (2010)
  • Author(s): 稲垣冬彦, 林佑次郎, 杵渕政彦, 宮腰直樹, 向智里
  • Organizer: 第8回次世代を担う有機化学シンポジウム
  • Place of Presentation: 日本薬学会長井記念ホール(東京都)
  • Year and Date: 2010-05-14
• [Presentation] Pauson-Khand反応を活用した効率的な多環状天然物の合成:(+)-ナカドマリンA及びメロシンの全合成 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 第8回次世代な担う有機化学シンポジウム
  • Place of Presentation: 長井記念ホール(東京都)
  • Year and Date: 2010-05-14
• [Presentation] 2位置換アザインドール合成法の開発 (2010)
  • Author(s): 稲垣冬彦, Montaser Ahmed SHAYKOON,向智里
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学(岡山県)
  • Year and Date: 2010-03-30
• [Presentation] Rh(I)触媒を活用したアルキン-アレニルシクロプロパンの[5+2]環化付加反応 (2010)
  • Author(s): 稲垣冬彦, 杉窪克哉, 宮下祐輔, 向智里
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学(岡山県)
  • Year and Date: 2010-03-30
• [Presentation] Stereoselective Total Syntheses of fiveLycopodium Alkaloids Based onPauson-Khand Reaction (2010)
  • Author(s): Yasunari Otsuka, Takashi Kozaka,Fuyuhiko Inagaki, Chisato Mukai
  • Organizer: 金沢大学薬学系 北京大学葯学院 国際学術交流協定に基づく合同セミナー2010
  • Place of Presentation: 石川県広坂庁舎(石川県)
  • Year and Date: 2010-03-12
• [Presentation] Pauson-Khand反応を活用した効率的な多環状天然物の合成; (+)-ナカドマリンA及びメロシンの全合成 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 金沢大学薬学シンポジウム
  • Place of Presentation: 金沢大学(石川県)
  • Year and Date: 2010-01-12
• [Presentation] Pauson-Khand反応を活用した効率的な多環状天然物の合成;(+)-ナカドマリンA及びメロシンの全合成 (2010)
  • Author(s): 稲垣冬彦
  • Organizer: 金沢大学薬学シンポジウム
  • Place of Presentation: 金沢大学(石川県)
  • Year and Date: 2010-01-12
• [Presentation] Total Stntheses of Nakadomarin A and Meloscine Based on Pauson-Khand Reaction (2009)
  • Author(s): Mukai, C
  • Organizer: Catalysis and Fine Chemicals 2009
  • Place of Presentation: Korea University (Korea)
  • Year and Date: 2009-12-16
• [Presentation] Fawcettimineの全合成 (2009)
  • Author(s): 大塚安成, 稲垣冬彦, 向智里
  • Organizer: 第35回反応と合成の進歩シンポジウム-ライフサイエンスを志向した理論、反応および合成-
  • Place of Presentation: 金沢市文化ホール(石川県)
  • Year and Date: 2009-11-16
• [Presentation] (±)-Meloscineの全合成研究 (2009)
  • Author(s): 林佑次郎, 稲垣冬彦, 松井祐美, 向智里
  • Organizer: 第39回複素環化学討論会
  • Place of Presentation: さわやか千葉県民プラザ(千葉県)
  • Year and Date: 2009-10-14
• [Presentation] (+)-ナカドマリンAの形式全合成 (2009)
  • Author(s): 稲垣冬彦
  • Organizer: 平成21年度有機合成化学北陸セミナー
  • Place of Presentation: 富山観光ホテル(富山県)
  • Year and Date: 2009-10-09
• [Presentation] C.Synthe ticstudies on (+)-nakadomarin A (2009)
  • Author(s): Inagaki, F.; Kinebuchi, M.; Miyakoshi,N.; Kitagaki, S.; Mukai
  • Organizer: 22ndInternational Congress on Heterocyclic Chemistry
  • Place of Presentation: Delta hotel, St.John's, Newfounland and Labrador(Canada)
  • Year and Date: 2009-08-06
• [Presentation] Synthetic studies on (+)-nakadomarin A (2009)
  • Author(s): Inagaki, F
  • Organizer: 22^<nd> International Congress on Heterocyclic Chemistry
  • Place of Presentation: Delta Hotel St. John's (Canada)
  • Year and Date: 2009-08-06