(S)-Propyl 5-((benzyloxy)methyl)-4-(1,2-dihydroxybutan-2-yl)-6-methoxypicolinate | 183433-75-2

• 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: (S)-Propyl 5-((benzyloxy)methyl)-4-(1,2-dihydroxybutan-2-yl)-6-methoxypicolinate
• 英文别名: propyl 4-[(2S)-1,2-dihydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate
• CAS: 183433-75-2
• 化学式: C₂₂H₂₉NO₆
• 分子量: 403.475
• InChiKey: DTLYVEUWMPUDLW-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-Propyl 5-((benzyloxy)methyl)-4-(1,2-dihydroxybutan-2-yl)-6-methoxypicolinate 在 palladium on activated charcoal 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 三甲基氯硅烷 、 4-acetoxy-2,2,6,6-tetramethylpiperidine-1-oxyl 、 氢气 、 碳酸氢钠 、 caesium carbonate 、 对甲苯磺酸 、 sodium iodide 、 potassium bromide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 甲苯 、 乙腈 、 三氟乙酸 为溶剂， 110.0 ℃ 、103.42 kPa 条件下， 反应 144.17h， 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 diacetate 、 sodium tetrahydroborate 、 四氧化锇 、 正丁基锂 、 三甲基氯硅烷 、 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 、 四甲基氯化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， -30.0~142.0 ℃ 、103.42 kPa 条件下， 反应 145.5h， 生成 (S)-Propyl 5-((benzyloxy)methyl)-4-(1,2-dihydroxybutan-2-yl)-6-methoxypicolinate
  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

• Application of immobilized lipase in production of camptosar (CPT‐11)
  作者：John C. Sih

  DOI：10.1007/bf02523499

  日期：1996.11

  Lipase fromPseudomonas cepaica (Amano, PS‐30) was immobilized on celite and used in organic solvent for the selective acylation of a key alcohol intermediate. The compound was transformed in the synthesis to the anticancer drug Camptosar (CPT‐11). Catalyst activity was influenced by the water content and method used to dry the catalyst. This resolution has been conducted on production scale with equal weight of recyclable catalyst.

  摘要 将来自天野假单胞菌（Amano，PS-30）的脂肪酶固定在天青石上，并在有机溶剂中用于选择性酰化一种关键的醇类中间体。该化合物在合成过程中转化为抗癌药物 Camptosar（CPT-11）。催化剂的活性受水含量和催化剂干燥方法的影响。这项研究是在使用等量可回收催化剂的生产规模上进行的。
• Practical Asymmetric Synthesis of (<i>S</i>)-4-Ethyl-7,8-dihydro-4-hydroxy-1<i>H</i>-pyrano[3,4-f]indolizine- 3,6,10(4<i>H</i>)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs
  作者：Kevin E. Henegar、Scott W. Ashford、Ted A. Baughman、John C. Sih、Rui-Lin Gu

  DOI：10.1021/jo970173f

  日期：1997.9.1

  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%.