神経突起伸展活性天然物ネオビブサニンの効率的合成法の開発および構造-活性相関

具有神经突生长活性的天然产物neovibusanin的高效合成方法和构效关系的开发

• 批准号: 16790023
• 负责人: 江角 朋之
• 金额: $ 2.37万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16790023/
• 关键词: ビブサン型ジテルペン類; 神経栄養因子様活性; ビブサニン類; 一酸化炭素挿入; 環化カルボニル化; carbonylative cyclization; ネオビブサニン; ビブサニン

現在までに我々はサンゴジュ(Viburnum awabuki)の葉部から80種を超えるビブサン型ジテルペン類を単離してきた.これらの中には,神経栄養因子様活性を初めとした特異な生物活性を示すものも多く存在し,幅広い分野の研究者から興味を集めている.今回,これらの研究に必要となる試料を迅速に提供出来るライブラリーの構築を目的とし,ビブサニン類に共通して含まれる11位4級不斉炭素構築法の開発を試みた.4-ペンテン-1-オールをジルコノセンジクロライドおよびトリメチルアルミニウムと反応させ,ヨウ素で処理する根岸法により(E)-ヨード-2-メチルアルケンへと変換後,水酸基をtert-ブチルジフェニルシリル基で保護し,さらに,10mol%テトラキストリフェニルホスフィンパラジウムを触媒とし,一酸化炭素雰囲気下でリチオ化した(S)-4-フェニル-2-オキサゾリジノンと反応させ,カルボニル挿入反応を含むカップリングを行い,α,β-不飽和カルボン酸のキラルオキサゾリジノン誘導体を得た.次にα,β-不飽和カルボン酸のキラルオキサゾリジノン誘導体を種々のビニル銅試薬と反応させたところ,目的とする1,4-ビニル付加体が高いジアステレオ選択的で得られることを見出した.現在,収率向上を目指し,検討中である.一方,ペンテンオールから出発しJohnson-Claisen転位を含む7段階の反応を経て上記1,4-ビニル付加体と合成化学的に等価なラセミの共通中間体を得た.共通中間体をアセチレン体へと導き,ヒドロホウ素化後,ヨウ化ビニル体との鈴木-宮浦反応に付し,立体選択的に(E,E)-共役ジエン体へと導いた.続いて,(E,E)-共役ジエン体に対し,Sharpless不斉ジヒドロキシル化を行ったところ,期待通り位置選択的に反応が進行し,(7S,8S)-ジオール体が得られた.さらに,両側鎖の修飾を行った後,一酸化炭素挿入による環化を試みたところ,望む11員環型中間体が得られることを見出した.一方,ラセミの共通中間体をヨウ素体へと導き,9-BBNを用いてヒドロホウ素化した後,一酸化炭素挿入による環化を試みたところ,望む7員環型中間体が得られることを見出した.現在,それぞれをビブサニンB,Cに導くことを検討中である.

At present, I am sorry to hear that the Viburnum awabuki department is currently in the middle of the 80th percussion period. The results show that there are many factors in the field, and the biological activity of the factor is different from that of the researchers in the field, and the biological activity shows that there is a lot of activity. This time, it is necessary to make sure that the necessary information is available quickly, and that the system contains 11 levels of carbon content at level 4. 4-level carbon system. 4-level carbon analysis system. 4-year-old carbon content. 4-level carbon analysis. After the preparation of the root method (E), the root method (2), the acid group (E), the root method (2), the acid group (E), the root method (2), the root method (E), the root method (2), the acid group (E), the root method (2), the acid group (E), the root method (2), the root method (E), the root method (2), the acid group (E), the acid group (10 mol%), the temperature (10 mol%), the temperature, the temperature and the temperature. An acidified carbon compound (S)-4-chlorinated carbon (S)-4-phenylethyl chloride (S)-2-phenylethyl chloride (2-D) is used in this paper. The secondary alpha, beta-and non-linear systems try to reduce the cost of health care. The purpose of this is to increase the number of users who have been selected for the first time. Now, the rate is up and down, and in the middle of the day. On the other hand, the Johnson-Claisen bit contains 7 segments and contains 7 segments. On the other hand, there are several parts in the synthetic chemistry of synthetic chemistry. It is common to have a common system, and after it has been refined, it will be converted into a stereoscopically selected material (Egraine E)-co-operative system. Please contact me, (E)-the co-service personnel will not be affected, and the Sharpless will not be able to do so. We look forward to the response of the selected location. (7s)-the system will be successful. After the treatment, the acidified carbon will be put into the environmental protection system, and it is hoped that 11 members of the environment will be able to get the carbon out of the plant. On the one hand, there is a common system in the system, and after the 9-BBN is used, the acidified carbon is put into the environmental protection system, and it is hoped that the environmental pollution system can be successfully processed. Now, I don't know what's going on in the middle of the day.

项目成果

First enatioselective synthesis of (-)-talaumidin, a neurotrophic diaryltetrahydrofuran-type lignan

首次对映选择性合成 (-)-talaumidin（一种神经营养性二芳基四氢呋喃型木酚素）

• 发表时间: 2006
• 期刊: Tetrahedron Letters 47
• 作者: Tomoyuki Esumi;Daisuke Hojyo;Haifeng Zhai;Yoshiyasu Fukuyama
• 通讯作者: Yoshiyasu Fukuyama

Cytotoxic iridoid aldehydes from Taiwanese Viburnum luzonicum

• DOI: 10.1248/cpb.53.125
• 发表时间: 2005-01-01
• 期刊: CHEMICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 1.7
• 作者: Fukuyama, Y;Minoshima, Y;Esumi, T
• 通讯作者: Esumi, T

Efficient synthesis of isoplagiochin D, a macrocycloc bis(bibenzyls), by utilizing an intramolecular Suzuki-Miyaura reaction

利用分子内 Suzuki-Miyaura 反应高效合成 isplagiochin D（一种大环双（联苄））

• 发表时间: 2004
• 期刊: Tetrahedron Lett. 45
• 作者: Tomoyuki Esumi;Mitsumasa Wada;Eri Mizushima;Norimasa Sato ほか
• 通讯作者: Norimasa Sato ほか

Neuroprotective effects of 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans

• DOI: 10.1248/bpb.28.289
• 发表时间: 2005-02-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Zhai, HF;Inoue, T;Fukuyama, Y
• 通讯作者: Fukuyama, Y

Iridoid glucosides and p-coumaroyl iridoids from Viburnum luzonicum and their cytotoxicity

• DOI: 10.1021/np040138l
• 发表时间: 2004-11-01
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Fukuyama, Y;Minoshima, Y;Esumi, T
• 通讯作者: Esumi, T