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年进行的研究结果总结如下： 1）利用铑-卡宾的C-H插入反应，建立了本实验室发现的前列环素潜在类似物异卡巴环素的新合成路线。合成中间体的合成以及用 1-烯基铅试剂直接引入 omega 链以构建二级合成中间体。2) 铑 (II) 催化剂的改进研究了C-H插入反应，制备了多种纯手性羧酸铑，用于构建手性分子。3)通过区域-(EPSILON和ZETA)-1-烯基酮的组合，建立了α-(EPSILON和ZETA)-1-烯基酮的高效选择性合成方法。以及将(EPSILON)-1-烯基和相应的ZETA基团立体控制引入到β-酮酯中，并随后还原去除酯官能团。4)高度立体选择性通过修饰涉及磷原子作为最佳糖基供体的离去基团进行糖苷化被广泛研究。我们建立的糖苷化方法已用于合成一些抗肿瘤药物，并不断研究其进一步的应用。

项目成果

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,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, N. Watanabe, and S. Ikegami: "Enantioselective Intramolecular C-H Insertion of alpha-Diazo beta-Keto Esters Catalyzed by Homochiral Rhodium(II) Carboxylates" Tetragedron Letters. 31(No. 36). 5173-5174 (1990)

S、Hashimoto、N. Watanabe 和 S. Ikegami：“同手性铑 (II) 羧酸盐催化的 α-重氮基 β-酮酯的对映选择性分子内 C-H 插入”Tetragedron Letters。

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。