Ethyl 2-(6'-cyano-5,5-dimethyl-5'-oxospiro[1,3-dioxane-2,1'-2,3-dihydroindolizine]-7'-yl)acetate | 208715-13-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Ethyl 2-(6'-cyano-5,5-dimethyl-5'-oxospiro[1,3-dioxane-2,1'-2,3-dihydroindolizine]-7'-yl)acetate
• CAS: 208715-13-3
• 化学式: C₁₈H₂₂N₂O₅
• 分子量: 346.383
• InChiKey: LFFNEUFVHSIBAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  88.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(6'-cyano-5,5-dimethyl-5'-oxospiro[1,3-dioxane-2,1'-2,3-dihydroindolizine]-7'-yl)acetate 在 吡啶 、 氢气 、 sodium hydride 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙酸酐 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 ethyl 2-(6-(acetoxymethyl)-5-oxo-2,3-dihydro-5H-spiro[indolizine-1,2'-[1,3]dioxolan]-7-yl)-4-phenylbutanoate
  参考文献：
  名称：

  胍-尿素双功能有机催化剂对内酯与乙烯基吡啶酮的不对称α-羟基氧化反应：（20S）-喜树碱类似物的关键中间体的催化对映选择性合成

  摘要：

  我们开发了（S）-4-乙基-6,6-（乙二氧基）-7,8-二氢-4-羟基-1 H-吡喃[3,4- f ]吲哚嗪-3,10的催化不对称合成（4 H）二酮（5 a），是（20 S）-喜树碱类似物的合成中间体。该合成的关键步骤是使用胍-脲双功能有机催化剂使具有乙烯基吡啶酮结构（8 a）的内酯不对称α-羟基化。本发明的氧化成功地应用于（+）的C20修饰的衍生物的合成- C20-desethylbenzylcamptothecin（13）。

  DOI：

  10.1002/chem.201303633

文献信息

• S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：US20030135049A1

  公开（公告）日：2003-07-17

  A process for preparing S type 2-substituted hydroxy-2-indolidinylbutyric ester compound [II]: 1 wherein R o is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of “R” (in which the nitrogen atom is protected), R1 and R2 are lower alkyl groups, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: 2 wherein the symbols are as defined above.

  一种制备S型2-取代羟基-2-吲哚丁酸酯化合物II的方法：其中Ro是氮杂环羧酸残基，具有“R”的绝对构型（其中氮原子受保护），R1和R2是较低的烷基基团，E是酯残基，该化合物是制备具有抗肿瘤活性的喜树碱衍生物的中间体，包括对2-取代羟基-2-吲哚丁酸乙酯化合物I进行2-乙基化，其中符号如上所定义。
• Stype 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US20020161231A1

  公开（公告）日：2002-10-31

  A process for preparing S type 2-substituted hydroxy-2-indolidinylbutyric ester compound [II]: 1 wherein R o is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of “R” (in which the nitrogen atom is protected), R1 and R2 are lower alkyl groups, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: 2 wherein the symbols are as defined above.

  一种制备S型2-取代羟基-2-吲哚丁酸酯化合物II的方法：其中Ro是氮杂环羧酸残基，具有“R”的绝对构型（其中氮原子受保护），R1和R2是低烷基基团，E是酯基残基，可用作制备具有抗肿瘤活性的喜树碱衍生物的中间体，该方法包括对2-取代羟基-2-吲哚乙酸酯化合物I进行2-乙基化，其中符号如上所定义。
• S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds as intermediates for camptothecin derivatives
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0845464A2

  公开（公告）日：1998-06-03

  A process for preparing S type 2-substituted hydroxy-2-indolidinyl-butyric ester compound [II]: wherein R° is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of "R"(in which the nitrogen atom is protected), R1 and R2 are lower alkyl group, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities,    comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: wherein the symbols are as defined above.

  一种制备 S 型 2-取代羟基-2-吲哚烷基丁酸酯化合物的工艺[II]： 其中 R°为绝对构型为 "R"（其中氮原子被保护）的含氮融合杂环羧酸残基，R1 和 R2 为低级烷基，E 为酯残基，可用作制备具有抗肿瘤活性的喜树碱衍生物的中间体、 包括 2-乙基化 2-取代羟基-2-吲哚乙酸酯化合物[I]： 其中符号如上定义。
• S-type 2-substituted hydroxy-2-indolinylbutyric ester compounds and process for preparation thereof
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP1236728A2

  公开（公告）日：2002-09-04

  A process for preparing an S type 4-substituted hydroxypyrano-indolidine compound of the formula (VII): wherein R° is a residue of a nitrogen-containing fused heterocyclic carboxylic acid having an absolute configuration of "R" which is obtained by removing hydroxy group from the carboxyl group of said carboxylic acid (in which the nitrogen atom contained in the residue is protected), is described. The process involves reduction, alkanoylation, nitrosation, rearrangement and intramolecular cyclization reactions.

  一种制备式(VII)的 S 型 4-取代羟基吡喃-吲哚化合物的工艺： 其中 R°是绝对构型为 "R "的含氮融合杂环羧酸的残余物，该残余物是通过从所述羧酸的羧基上去除羟基而得到的（其中残余物中所含的氮原子受到保护）。 该过程包括还原、烷酰化、亚硝基化、重排和分子内环化反应。
• Process for the preparation of s-type 4-substituted hydroxypyranoindolidine compounds
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP1528062A2

  公开（公告）日：2005-05-04

  A process for preparing an S type 4-substituted hydroxypyrano-indolidine compound of the formula (VII) : wherein Ro is a residue of a nitrogen-containing fused heterocyclic carboxylic acid having an absolute configuration of "R" which is obtained by removing hydroxy group from the carboxyl group of said carboxylic acid (in which the nitrogen atom contained in the residue is protected), is described. The process involves reduction, alkanoylation, nitrosation, rearrangement and intramolecular cyclization reactions.

  一种制备式(VII)的 S 型 4-取代羟基吡喃-吲哚化合物的工艺： 其中，Ro 是绝对构型为 "R "的含氮融合杂环羧酸的残余物，该残余物是通过从所述羧酸的羧基上去除羟基而得到的（其中残余物中所含的氮原子受到保护）。 该过程包括还原、烷酰化、亚硝基化、重排和分子内环化反应。