Development of practical methods for the synthesis of taxane diterpenoids

紫杉烷二萜合成实用方法的开发

• 批准号: 09555286
• 负责人: SAITO Seiki
• 金额: $ 8.58万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09555286/
• 关键词: Taxol; cyclohexane-1,3-dione; consecutive Michael-Claisen reaction; ビナコール環化; タキソ-ル; 8員環合成; 分子内[3+2]環化付加反応

We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3+3]) promising for the synthesis of a cyclohexane-1, 3-dione derivatives from non-activated simple ketones and enoates, and evaluated its potential in modern organic synthesis. The reaction conditions employing the ketones (1.2 equiv), enoate (1.0 equiv), and t-BuOK (1.2 equiv) in THF as a solvent at temperature range of 0℃ to 40℃ have been established. Twenty to thirty examples were demonstrated to be effective under such conditions including the synthesis of a taxol A, C-ring synthons available in multi-gram quantities. The reactions exhibited remarkable regioselectivity that the Michael addition proceeded through nucleophilic attack by more hindered site of the ketones without exceptions, which, in turn, means that Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. In addition, taking advantages of the MC- [3+3] process, a few useful methods for the synthesis of six membered carbocyclic compounds have also been developed. A number of control experiments have been conducted to provide strong supporting information for the mechanism of this MC-[3+3] process.

我们重新回顾了传统的连续Michael-Claisen [3 + 3]（MC-[3+3]）工艺，并对其在现代有机合成中的应用前景进行了评价。确定了在0℃至40℃的温度范围内，使用酮（1.2当量）、烯酸酯（1.0当量）和t-BuOK（1.2当量）在THF中作为溶剂的反应条件。二十至三十个实例被证明是有效的，在这样的条件下，包括合成紫杉醇A，C-环紫杉醇可在多克数量。反应表现出明显的区域选择性，Michael加成反应无一例外地是通过酮的受阻位亲核进攻进行的，这意味着Claisen缩合反应导致酮的受阻位与烯酸酯的酰基碳之间形成了碳-碳键.此外，利用MC- [3+3]过程，还发展了几种合成六元碳环化合物的有效方法。大量的控制实验为MC-[3+3]过程的机理提供了有力的支持信息。

项目成果

Ishikawa, T. ; Kudoh, T. ; Shigemori, K. ; Saito, S.: "Application of the Silicon-Tether Strategy for Controlling the Regioselectivity and Diastereoselectivity of Intramolecular Nitrone Cycloadditions for Aminopolyol Synthesis."J.Am.Chem.Soc.. 112. 7633-7

石川，T.；

Teruhiko Ishikawa, Eiji Uedo, Rie Tani, Seiki Saito: "Aromatization of Enamines Promoted by a Stoichiometric Amount of Palladium (II) Salts : A Novel Method for the Synthesis of Aromatic Amines"J.Org.Chem.. 186-191 (2001)

Teruhiko Ishikawa、Eiji Uedo、Rie Tani、Seiki Saito：“化学计量的钯 (II) 盐促进烯胺的芳香化：合成芳香胺的新方法”J.Org.Chem.. 186-191 (2001)

Teruhiko Ishikawa,Keita Nagai,Takayuki Kudoh and Seiki Saito: "Chiral Lewis Acid-Hydroxylamine Hybrid Reagent for Enantioselective Michael Addition Reaction Directed toward β-Amino Acids Synthesis"Synlett. 1291-1293 (1998)

Teruhiko Ishikawa、Keita Nagai、Takayuki Kudoh 和 Seiki Saito：“针对 β-氨基酸合成的对映选择性迈克尔加成反应的手性路易斯酸-羟胺混合试剂”Synlett 1291-1293 (1998)。

斎藤清機,石川彰彦: "隣接ジオール制御素子による不斉空間の構築とニトロン-オレフィン[3+2]環化付加反応の立体制御への応用"有機合成化学協会誌. 56. 86-95 (1998)

Seiki Saito、Akihiko Ishikawa：“使用相邻二醇控制元件构建不对称空间及其在硝酮-烯烃[3+2]环加成反应立体控制中的应用”有机合成化学学会杂志 56. 86-95 (1998)。

Teruhiko Ishikawa, Ryuichiro Kadoya, Massaki Arai, Haruka Takahashi, Yumi Kaisi, Tomohiro Mizuta, Kazusa Yoshikai and Seiki Saito: "Revisiting [3+3] Route to 1,3-Cyclohexanedione Frameworks : Missing Opportunity in Organic Synthesis for Sixty Years and Hi

Teruhiko Ishikawa、Ryuichiro Kadoya、Massaki Arai、Haruka Takahashi、Yumi Kaisi、Tomohiro Mizuta、Kazusa Yoshikai 和 Seiki Saito：“重访 [3 3] 1,3-环己二酮框架路线：六十年有机合成中缺失的机遇