(4R)-4-{1-[(S)-(tert-butoxycarbonyl)amino]-2-phenylethyl}-γ-butyrolactone | 135130-98-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R)-4-{1-[(S)-(tert-butoxycarbonyl)amino]-2-phenylethyl}-γ-butyrolactone
• 英文别名: [1S-(5-oxo-tetrahydrofuran-2-yl)-2R-phenylethyl]-carbamic acid, tert-butyl ester；tert-butyl (S)-1-((R)-tetrahydro-5-oxofuran-2-yl)-2-phenylethylcarbamate；[(1S)-2-Phenyl-1-[(2R)-tetrahydro-5-oxo-2-furanyl]ethyl]carbamic Acid 1,1-Dimethyethyl Ester；tert-butyl N-[(1S)-1-[(2R)-5-oxooxolan-2-yl]-2-phenylethyl]carbamate
• CAS: 135130-98-2
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: YZDUNYUENNWBRE-UONOGXRCSA-N

物化性质

• 沸点：
  490.5±28.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-4-{1-[(S)-(tert-butoxycarbonyl)amino]-2-phenylethyl}-γ-butyrolactone 在 咪唑 、 氢氧化钾 、 lithium hydroxide 、 氯化亚砜 、 (PhO)PON₃ 、 四丁基氟化铵 、 水 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 SSS-2,5-diamino-1,6-diphenyl-3-hexanol
  参考文献：
  名称：

  蛋白酶抑制剂二肽等排体的不对称二羟基化途径：利托那韦核心单元的对映选择性合成。

  摘要：

  以 Sharpless 不对称羟基化为关键步骤，完成了利托那韦二肽电子等排体的对映选择性合成。

  DOI：

  10.1039/a902518i
• 作为产物：
  描述：

  1-苄基-2,3-环氧正丙基-氨基甲酸叔丁酯 在 lithium hydroxide 、 sodium ethanolate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 (4R)-4-{1-[(S)-(tert-butoxycarbonyl)amino]-2-phenylethyl}-γ-butyrolactone
  参考文献：
  名称：

  Stereoselective Synthesis of Photoreactive Peptidomimetic γ-Secretase Inhibitors

  摘要：

  The first asymmetric synthesis of novel, potent photoreactive gamma-secretase inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing gamma-secretase activity in the plasma membrane of intact cells.

  DOI：

  10.1021/jo0486948

文献信息

• Synthesis of a complete series of C-4 fluorinated phe-gly mimetics
  作者：Wei Berts、Kristina Luthmana

  DOI：10.1016/s0040-4020(99)00865-0

  日期：1999.11

  mono- and difluorinated Phe-Gly methyl ester derivatives has been synthesized using facile methods. Diastereomeric allylic alcohol derivatives were used as key intermediates, cis- And trans-aziridine derivatives were synthesized in high yields from the diastereomeric alcohols using Mitsunobu conditions. The aziridines were treated with diethylaminosulfur trifluoride (DAST) at room temperature, which

  使用简便的方法合成了Boc保护的烯丙基单和二氟化的Phe-Gly甲基酯衍生物的完整系列。非对映体烯丙醇衍生物用作关键中间体，顺式-和反式-氮丙啶衍生物在使用Mitsunobu条件下以高收率由非对映体醇合成。氮丙啶在室温下用二乙基氨基三氟化硫（DAST）处理，这导致立体选择性开环，产生了单氟化衍生物。使用DAST由γ-酮酸酯衍生物合成二氟代等位异构体。还合成了相应系列的饱和氟化衍生物。
• Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond. I. Preparation of Four Diastereoisomeric (2R or 2S,4R or 4S,5S)-2-Benzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylhexanoic Acids
  作者：Jaroslav Litera、Miloš Buděšínský、Ján Urban、Milan Souček

  DOI：10.1135/cccc19980231

  日期：——

  By two separate routes were prepared four diastereoisomers of (2R or 2S,5R or 5S)-3-benzyl-5-(1S)- [(tert-butoxycarbonyl)amino]-2-phenylethyl}tetrahydrofuran-2-ones (11, 12, 17 and 18). Since the furanones were derived from (S)-phenylalanine, absolute configurations of all chiral carbon atoms could be deduced from their ¹H NMR spectra. The furanones were easily hydrolyzed to four (2R or 2S,4R or 4S,5S)-2-benzyl-5- [(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylbutanoic acids (20-23), hydroxyethylene isosteres of Phe-Phe peptide bond.

  通过两条不同的途径，制备了四个对映异构体(2R或2S,5R或5S)-3-苄基-5-(1S)-[(叔丁氧羰基)氨基]-2-苯乙基}四氢呋喃-2-酮(11、12、17和18)。由于呋喃酮是由(S)-苯丙氨酸衍生而来的，所有手性碳原子的绝对构型可以从它们的1H NMR谱中推断出来。这些呋喃酮容易水解成四个(2R或2S,4R或4S,5S)-2-苄基-5-[(叔丁氧羰基)氨基]-4-羟基-6-苯基丁酸(20-23)，是Phe-Phe肽键的羟基乙烯同分异构体。
• Stereocontrolled addition of propionate homoenolate equivalents to chiral α-amino aldehydes
  作者：Ann E. Decamp、Alan T. Kawaguchi、R.P. Volante、Ichiro Shinkai

  DOI：10.1016/s0040-4039(00)85983-3

  日期：1991.4

  A highly efficient route is presented for preparation of the medicinally important hydroxyester and lactone intermediates 1 and 2 from chiral α-amino aldehydes via homoenolate methodology. Several reaction variables were found to influence the ratio of chelation controlled versus Felkin-Ahn products.

  提出了一种通过手性α-氨基醛通过均烯酸酯方法制备具有医学重要性的羟基酯和内酯中间体1和2的高效途径。发现一些反应变量影响螯合受控产物与Felkin-Ahn产物的比率。
• A stereocontrolled synthesis of 2 R -benzyl-5 S - tert -butoxycarbonylamino-4 R -( tert -butyldimethylsilanyloxy)-6-phenyl-hexanoic acid (Phe–Phe hydroxyethylene dipeptide isostere)
  作者：Alan Nadin、José M Sánchez López、Joseph G Neduvelil、Steven R Thomas

  DOI：10.1016/s0040-4020(00)01167-4

  日期：2001.2

  2R-Benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6-phenyl-hexanoic acid, a hydroxyethylene dipeptide isostere corresponding to Phe–Phe, has been synthesized in a practical, stereocontrolled fashion from (l)-phenylalanine.

  2 - [R苯甲基-5-小号-叔丁氧羰基-4 - [R - （叔-butyldimethylsilanyloxy）-6-苯基己酸，羟基亚乙基二肽电子等排体对应成Phe-PHE，在从实际的，立体控制方式已被合成（升）-苯丙氨酸。
• Stereoselective Synthesis of Photoreactive Peptidomimetic γ-Secretase Inhibitors
  作者：Jiong Chun、Ye Ingrid Yin、Guangli Yang、Leonid Tarassishin、Yue-Ming Li

  DOI：10.1021/jo0486948

  日期：2004.10.1

  The first asymmetric synthesis of novel, potent photoreactive gamma-secretase inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing gamma-secretase activity in the plasma membrane of intact cells.