Synthetic Studies on Biologically Active Substances for Retaining Homeostasis

维持体内平衡的生物活性物质的合成研究

• 批准号: 01470141
• 负责人: IKEGAMI Shiro
• 金额: $ 3.9万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01470141/
• 关键词: Prostacyclin; Isocarbacyclin; Rhodium(II) carboxylates; Carbenoid; Organolead reagents; Glycosylation; Glycosides; beta-Keto esters; プロスタグランジン; ロイコトリエン; リポキシン; グルコシド

A result of our research carried out in 1989-1990 is summarized as follows.1) A new synthetic route to isocarbacyclin which is a potential analogue of prostacyclin discovered in our laboratory was established by employing a C-H insertion reaction of rhodium-carbenoid for the synthesis of a synthetic intermediate and the direct introduction of a omega chain with a 1-alkenyllead reagent for the construction of a secondary synthetic intermediate.2) An improvement of rhodium (II) catalyst for a C-H insertion reaction was studied and a variety of homochiral rhodium carboxylates were prepared for the construction of chiral molecules.3) An efficient and selective synthesis of alpha- (EPSILON and ZETA) -1-alkenyl ketones was established by the combination of a regio- and stereocontrolled introduction of (EPSILON) -1-alkenyl and the corresponding ZETA groups to beta-Keto esters and subsequent reductive removal of ester functionality.4) A higly stereoselective glycosidation by modifying leaving groups involving a phosphorus atom as the best glycosyl donor was extensively studied. The glycosidation method we established was applied to synthesize some anti-tumor agent and further applications are continuously investigated.

我们在1989-1990年的研究工作中，发现了一种新的合成前列环素类似物异碳环素的方法，它是通过铑-卡宾的C-H插入反应合成中间体，然后直接引入一个1-羟基的ω链，然后再将该中间体与一个1-羟基的ω链连接起来，最后得到一个新的产物。2）改进了铑（II）催化C-H插入反应的催化剂，制备了多种纯手性羧酸铑酯，用于手性分子的构建; 3）高效、选择性地合成了α-羟基铑（Ⅱ），并在此基础上合成了α-羟基铑（Ⅱ）的手性衍生物。（EPSILON和ZETA）-1-烯基酮是通过将（EPSILON）-1-烯基和相应的ZETA基团区域和立体控制地引入β-酮酯并随后还原除去酯官能团而建立的。4）广泛研究了通过修饰涉及磷原子作为最佳糖基供体的离去基团的高立体选择性糖苷化。我们建立的糖苷化方法已用于合成一些抗肿瘤药物，并进一步研究其应用。

项目成果

S.Hashimoto,Y.Miyazaki,T.Shinoda,and S.Ikegami: "A Versatile and Convenient Method for the Preparation of alphaー(Z)ーlーAlkenyl Ketones from betaーKeto Benzyl Esters" J.Chem.Soc.,Chem.Commun.1100-1102 (1990)

S. Hashimoto、Y. Miyazaki、T. Shinoda 和 S. Ikegami：“从 β-酮苄基酯制备 α-(Z)-l-烯基酮的通用且方便的方法”J.Chem.Soc。 ,Chem.Commun.1100-1102 (1990)

S.Hashimoto,Y.Miyazaki,T.Shinoda,and S.Ikegami: "A Controlled Synthesis of alfaー(E)ー1ーAlkenyl Ketones from betaーKeto Benzyl Esters." Tetrahedron Letters. 30. 7195-7198 (1989)

S. Hashimoto、Y. Miyazaki、T. Shinoda 和 S. Ikegami：“从 β-酮四面体酯中控制合成α-(E)-1-烯基酮。”30. 7195-7198 (1989) ）

S.Hashimoto,T.Honda,and S.Ikegami: "A Rapid and Efficient Synthesis of 1,2ーtransーbetaーLinked Glycosides via Benzylーor BenzoylーProtected Glycopyaanosyl Phosphates" J.Chem.Soc.,Chem.Commun.685-687 (1989)

S.Hashimoto、T.Honda 和 S.Ikegami：“通过苄基或苯并保护的糖基磷酸酯快速高效合成 1,2-反式-β-连接糖苷” J.Chem.Soc.,Chem.Commun .685-687 (1989)

S.Hashimoto,T.Honda,and S.Ikegami: "An Extremely Mild and General Method for the Stereocontrolled Construction of 1,2ーcisーGlycosidic Linkages via SーGlycopyranosyl Phosphorodiamidimidothioates" Tetradedron Letters. 31. 4769-4772 (1990)

S. Hashimoto、T. Honda 和 S. Ikegami：“通过 S-吡喃糖基磷酸二脒基酯立体控制构建 1,2-顺式糖苷键的极其温和且通用的方法”Tetradedron Letters 31. 4769-4772 (1990)。

S. Hashimoto, Y. Miyazaki, T. Shinoda, and S. Ikegami: "A Controlled Synthesis of alpha-(E)-1-Alkenyl Ketones from beta-Keto Benzyl Esters" Tetrahedrom Lett.30. 7195-7198 (1989)

S. Hashimoto、Y. Miyazaki、T. Shinoda 和 S. Ikegami：“从 β-酮苄酯中控制合成 α-(E)-1-烯基酮”Tetrahedrom Lett.30。