(1'S,2R,3S,3'S,5S)-5-(3-butylcarbamoyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-(4-methoxyphenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester | 441794-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1'S,2R,3S,3'S,5S)-5-(3-butylcarbamoyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-(4-methoxyphenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: 5S-(3-butylcarbamoyl-1S-hydroxy-4S-methylpentyl)-3S-isopropyl-2R-(4-methoxyphenyl)pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2R,3S,5S)-5-[(1S,3S)-3-(butylcarbamoyl)-1-hydroxy-4-methylpentyl]-2-(4-methoxyphenyl)-3-propan-2-ylpyrrolidine-1-carboxylate
• CAS: 441794-87-2
• 化学式: C₃₀H₅₀N₂O₅
• 分子量: 518.737
• InChiKey: ZMUUWPAAIVBBJR-IRGGMKSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1'S,2R,3S,3'S,5S)-5-(3-butylcarbamoyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-(4-methoxyphenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以60%的产率得到tert-butyl (3S,5S,6S,8S)-8-(butylcarbamoyl)-6-hydroxy-3-(4-methoxybenzyl)-2,9-dimethyldecan-5-ylcarbamate
  参考文献：
  名称：

  全合成“ Aliskiren”：高血压临床实践中的第一种肾素抑制剂

  摘要：

  我们报告了从目前的“异丙基卡隆”开始使用高度立体控制的方法，向阿利吉仑（“阿利吉仑”）迈进的“宏观周期路线”，阿利吉仑目前是一种用于治疗高血压的药物。合成的重点包括具有挑战性的RCM反应，该反应可产生九元不饱和内酯，高度立体选择性的催化Du Bois叠氮化和对邻氨基氨基醇的区域和非对映选择性氮丙啶开环。

  DOI：

  10.1021/ol100427v
• 作为产物：
  描述：

  5S-[4S-(1-hydroxy-1-methylethyl)-5-oxotetrahydrofuran-2S-yl]-3S-isopropyl-2R-(4-methoxyphenyl)pyrrolidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 五氯化磷 、 氢气 、 三甲基铝 作用下， 以 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 0.5h， 生成 (1'S,2R,3S,3'S,5S)-5-(3-butylcarbamoyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-(4-methoxyphenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  The Power of Visual Imagery in Synthesis Planning. Stereocontrolled Approaches to CGP-60536B, a Potent Renin Inhibitor

  摘要：

  Two strategies were developed toward the stereocontrolled synthesis of 8-aryl-3-hydroxy-4-amino2,7-diisopropyloctanoic acids with predetermined stereogenic centers. This is a generic motif in a new class of potent inhibitors of the enzyme renin, exemplified by CGP-60536B. The synthesis relies on the utilization of L-pyroglutamic acid as chiron, and proceeds through the incorporation of required functionality by exploiting internal induction. One of the strategies shows the power of visual imagery in synthesis planning, akin to a Dali-like representation of objects that can be viewed in more than one way. Thus, the entire carbon skeleton of the target molecule is encompassed in a partially functionalized bicyclic indolizidinone precursor. In a second strategy, an intermediate common to the first approach is elaborated into an appended gamma-lactone which is alkylated through enolate chemistry and ultimately transformed into the intended target compound. X-ray crystallography was used to corroborate the structures and stereochemistries of several intermediates.

  DOI：

  10.1021/jo011184i

文献信息

• Conception and Evolution of Stereocontrolled Strategies toward Functionalized 8-Aryloctanoic Acids Related to the Total Synthesis of Aliskiren
  作者：Stephen Hanessian、Etienne Chénard、Sébastien Guesné、Jean-Philippe Cusson

  DOI：10.1021/jo5015195

  日期：2014.10.17

  A detailed account is given describing the approaches used toward the total synthesis of aliskiren. In particular, ring-closing metathesis with the Hoveyda–Grubbs catalyst accelerates the formation of a 9-membered lactone from an (R)-ester. The diastereomeric (S)-ester leads to the formation of dimeric dilactones, which were characterized by X-ray analysis and chemical conversions.

  详细描述了用于合成阿利吉仑的方法。特别是，使用Hoveyda-Grubbs催化剂进行的闭环复分解加速了由（R）酯形成9元内酯的过程。非对映体（S）-酯导致形成二聚二内酯，其特征在于X射线分析和化学转化。
• Total Synthesis of “Aliskiren”: The First Renin Inhibitor in Clinical Practice for Hypertension
  作者：Stephen Hanessian、Sébastien Guesné、Etienne Chénard

  DOI：10.1021/ol100427v

  日期：2010.4.16

  We report a “macrocycle route” toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common “isopropyl chiron”. Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine

  我们报告了从目前的“异丙基卡隆”开始使用高度立体控制的方法，向阿利吉仑（“阿利吉仑”）迈进的“宏观周期路线”，阿利吉仑目前是一种用于治疗高血压的药物。合成的重点包括具有挑战性的RCM反应，该反应可产生九元不饱和内酯，高度立体选择性的催化Du Bois叠氮化和对邻氨基氨基醇的区域和非对映选择性氮丙啶开环。
• The Power of Visual Imagery in Synthesis Planning. Stereocontrolled Approaches to CGP-60536B, a Potent Renin Inhibitor
  作者：Stephen Hanessian、Stephen Claridge、Shawn Johnstone

  DOI：10.1021/jo011184i

  日期：2002.6.1

  Two strategies were developed toward the stereocontrolled synthesis of 8-aryl-3-hydroxy-4-amino2,7-diisopropyloctanoic acids with predetermined stereogenic centers. This is a generic motif in a new class of potent inhibitors of the enzyme renin, exemplified by CGP-60536B. The synthesis relies on the utilization of L-pyroglutamic acid as chiron, and proceeds through the incorporation of required functionality by exploiting internal induction. One of the strategies shows the power of visual imagery in synthesis planning, akin to a Dali-like representation of objects that can be viewed in more than one way. Thus, the entire carbon skeleton of the target molecule is encompassed in a partially functionalized bicyclic indolizidinone precursor. In a second strategy, an intermediate common to the first approach is elaborated into an appended gamma-lactone which is alkylated through enolate chemistry and ultimately transformed into the intended target compound. X-ray crystallography was used to corroborate the structures and stereochemistries of several intermediates.