5S-[4S-(1-hydroxy-1-methylethyl)-5-oxotetrahydrofuran-2S-yl]-3S-isopropyl-2R-(4-methoxyphenyl)pyrrolidine-1-carboxylic acid tert-butyl ester | 441794-84-9

• 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: 5S-[4S-(1-hydroxy-1-methylethyl)-5-oxotetrahydrofuran-2S-yl]-3S-isopropyl-2R-(4-methoxyphenyl)pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (2R,3S,5S)-5-[(2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxooxolan-2-yl]-2-(4-methoxyphenyl)-3-propan-2-ylpyrrolidine-1-carboxylate
• CAS: 441794-84-9
• 化学式: C₂₆H₃₉NO₆
• 分子量: 461.599
• InChiKey: GFCUQJDYEDELNM-WIYBCGNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以80%的产率得到5S-(4S-isopropenyl-5-oxotetrahydrofuran-2S-yl)-3S-isopropyl-2R-(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
• 作为产物：
  描述：

  Boc-L-焦谷氨酸甲酯 在 palladium on activated charcoal 咪唑 、 4-二甲氨基吡啶 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium tetrahydroborate 、 正丁基锂 、 copper bromide dimethyl sulfide complex 、 碘苯二乙酸 、 三氟化硼乙醚 、 氢气 、 二异丁基氢化铝 、 对甲苯磺酸 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， -78.0~20.0 ℃ 、275.8 kPa 条件下， 反应 42.0h， 生成 5S-[4S-(1-hydroxy-1-methylethyl)-5-oxotetrahydrofuran-2S-yl]-3S-isopropyl-2R-(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

• 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.