propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate | 183434-02-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate
• 英文别名: propyl (4S)-4-ethyl-4-hydroxy-3,8-dioxo-1,7-dihydropyrano[3,4-c]pyridine-6-carboxylate
• CAS: 183434-02-8
• 化学式: C₁₄H₁₇NO₆
• 分子量: 295.292
• InChiKey: BBTZLXDLDUPAAC-AWEZNQCLSA-N

物化性质

• 熔点：
  187.6-189 °C
• 沸点：
  610.6±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate 在 caesium carbonate 、 对甲苯磺酸 作用下， 以 溶剂黄146 、 二甲基亚砜 、 甲苯 、 三氟乙酸 为溶剂， 反应 41.0h， 生成 7-乙基-10-羟基喜树碱
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f
• 作为产物：
  描述：

  柠嗪酸 在 palladium on activated charcoal palladium diacetate 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 sodium tetrahydroborate 、 四氧化锇 、 正丁基锂 、 三甲基氯硅烷 、 4-acetoxy-2,2,6,6-tetramethylpiperidine-1-oxyl 、 十二/十四烷基二甲基氧化胺 、 POPCl₃ 、 PS-30 catalyst 、 巴拉松 、 potassium tert-butylate 、 四丁基氯化铵 、 氢气 、 四甲基氯化铵 、 碳酸氢钠 、 potassium carbonate 、 sodium iodide 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 叔丁醇 为溶剂， -30.0~142.0 ℃ 、103.42 kPa 条件下， 反应 248.67h， 生成 propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f

文献信息

• Process for producing tricyclic ketone
  申请人：Nishiyama Hiroyuki

  公开号：US20090023927A1

  公开（公告）日：2009-01-22

  In order to efficiently supply CPT, which is a starting compound of irinotecan hydrochloride and a variety of camptothecin derivatives, by a practical total synthesis, the invention provides a means of efficiently preparing a tricyclic ketone that corresponds to a CDE ring moiety of a camptothecin (CPT) skeleton.

  为了通过实际的全合成高效地供应伊立替康盐酸盐的起始化合物CPT和各种喜树碱衍生物，本发明提供了一种有效制备对应于喜树碱（CPT）骨架中的CDE环部分的三环酮的方法。
• PROCESS FOR PRODUCING TRICYCLIC KETONE
  申请人：Nishiyama Hiroyuki

  公开号：US20120041204A1

  公开（公告）日：2012-02-16

  In order to efficiently supply CPT, which is a starting compound of irinotecan hydrochloride and a variety of camptothecin derivatives, by a practical total synthesis, the invention provides a means of efficiently preparing a tricyclic ketone that corresponds to a CDE ring moiety of a camptothecin (CPT) skeleton.

  为了通过实用的全合成方法高效地合成伊立替康盐酸盐和多种喜树碱衍生物的起始化合物CPT，本发明提供了一种有效制备与喜树碱（CPT）骨架的CDE环部分相应的三环酮的方法。
• METHOD OF SYNTHESIZING CAMPTOTHECIN-RELATING COMPOUNDS
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP1378505B1

  公开（公告）日：2014-11-05
• Method of synthesizing camptothecin-relating compounds
  申请人：Ogawa Takanori

  公开号：US20070010674A1

  公开（公告）日：2007-01-11

  The present invention is to prepare efficiently 2′-amino-5′-hydroxypropiophenone corresponding to the AB-ring part of camptothecin (CPT) skeleton and a tricyclic ketone corresponding to the CDE-ring part in order to provide efficiently CPT by the total synthesis, which is a starting material for irinotecan hydrochloride and various kinds of camptothecin derivatives, and to provide stably CPT and its derivatives.
• US7378555B2
  申请人：——

  公开号：US7378555B2

  公开（公告）日：2008-05-27