多連続不斉中心の新規構築法の開発:Stemonaアルカロイドの不斉合成研究

多连续不对称中心构建新方法的发展：百部生物碱的不对称合成研究

• 批准号: 00J01851
• 负责人: 古徳 直之
• 金额: $ 1.92万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-00J01851/
• 关键词: 不斉非対称化; 不斉合成; Stemonaアルカロイド; N-SMase; scyphostatin; 速度論的光学分割法

申請者は、当研究室で開発した光学活性C_2対称ジオールを不斉源とする分子内ハロエーテル化反応を用いる、σ対称シクロヘキサジエンアセタールの不斉非対称化によって得られる光学活性シクロヘキセン誘導体を出発物質とした、光学活性天然物の不斉合成研究を目的として研究を行っている。今回申請者は、Stemonaアルカロイドの代表的な化合物であるstenineの構造異性体の合成に興味を抱き、検討を行った結果、立体選択的なアルキル側鎖の導入から、分子内aza-Wittig反応と続くイミンの還元による五員環の構築、分子内縮合による七員環の閉環反応などを経て、stenineの9a位エピマー、9a-epi-stenineの不斉合成に成功した。一方、新たなターゲットとして、中性スフィンゴミエリナーゼ(N-SMase)阻害作用を有する生物活性天然物scyphostatinの合成研究を行い、検討の結果、二酸化セレンによる位置および立体選択的なアリル位の酸化を足掛かりとし、ジアステレオ選択的なエポキシ化などを経て、scyphostatinのエポキシシクロヘキセノン部に相当する化合物の立体選択的な合成に成功した。また、以前報告した、分子内ハロエーテル化反応を鍵反応とし、光学活性C_2対称ジオールを不斉源とするノルボルネンアルデヒド類の速度論的光学分割法が、3位にendo置換基を有する基質にも適用可能であることを明らかにした。

The applicant, when the laboratory starts the optical activity C02, it is known that the source is the source of the chemical reaction in the molecule, and the sigma is known to be the source of the optical activity. Objective to study the synthesis of optically active natural substances. The compounds represented by the current applicant, Stemona and stenine were used to synthesize phenotypic compounds, the results of the experiments, the results of the stereo selection, the results of the stereoselective response, the intramolecular aza-Wittig response, the addition of the five-member molecule, the intramolecular synthesis of the seven-member complex, the response of the stenine at position 9a, and so on. 9a-epi-stenine did not synthesize successfully. The blocking effect of N-SMase on the synthesis of bioactive natural substances, the results of the study, the results of the synthesis of biologically active natural substances, the results of the synthesis of biologically active natural substances, the results of the synthesis of biologically active natural substances, the results of the synthesis of biologically active natural substances, the results of the synthesis of biologically active natural substances, the results of the synthesis of bioactive natural substances, the results of the synthesis of bioactive natural substances, the results of the synthesis of biologically active natural substances, the results of the synthesis of biologically active natural substances, the results of dicarboxylic acid, the position of the stereo selection, the position of the stereo option, the position of the stereo option, the position of the stereo selection, the acidizing position of the stereo selection, and so on, the results of the study on the synthesis of bioactive natural substances, the results of the study on the synthesis of bioactive natural substances were studied. Scyphostatin was successfully synthesized by stereospecific selection of compounds. For example, previous reports, intra-molecular chemical reactions, optical activity Czochralski, optical activity Czochralski, optical slicing method for speed analysis, 3-bit endo base station, and the possibility that the data may be used.

项目成果

Hiromichi Fujioka: "Concise asymmetric synthesis of a model compound, (4S,5S,6S)-6-(2,2-dimethoxy)ethyl-4,5-epoxy-6-hydroxy-2-cyclohexenone, for the cyclohexenone core of scyphostatin"Tetrahedron Letters. 43. 4825-4828 (2002)

Hiromichi Fujioka：“模型化合物 (4S,5S,6S)-6-(2,2-二甲氧基)乙基-4,5-环氧-6-羟基-2-环己烯酮的简明不对称合成，用于环己烯酮核心

Hiromichi Fujioka: "Kinetically Controlled Optical Resolution of Racemic Norbornene Aldehyde Derivatives"Chirality. 15. 60-67 (2003)

Hiromichi Fujioka：“外消旋降冰片烯醛衍生物的动力学控制光学分辨率”手性。