(6R)-4-hydroxy-3-[1-(3-nitrophenyl)-1-propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | 215317-22-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (6R)-4-hydroxy-3-[1-(3-nitrophenyl)-1-propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one
• 英文别名: (6R)-5,6-Dihydro-4-hydroxy-3-[(1R)-1-(3-nitrophenyl)propyl]-6-(2-phenylethyl)-6-propyl-2H-pyran-2-one；(2R)-4-hydroxy-5-[(1R)-1-(3-nitrophenyl)propyl]-2-(2-phenylethyl)-2-propyl-3H-pyran-6-one
• CAS: 215317-22-9
• 化学式: C₂₅H₂₉NO₅
• 分子量: 423.509
• InChiKey: IVSBNHGCCSIIRX-PXDATVDWSA-N

物化性质

• 沸点：
  587.2±50.0 °C(Predicted)
• 密度：
  1.193±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6R)-4-hydroxy-3-[1-(3-nitrophenyl)-1-propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 (6R)-3-[(1R)-1-(3-Aminophenyl)propyl]-5,6-dihydro-4-hydroxy-6-(2-phenylethyl)-6-propyl-2H-pyran-2-one
  参考文献：
  名称：

  A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

  摘要：

  PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.

  DOI：

  10.1021/jo9809229
• 作为产物：
  描述：

  methyl (5R)-5-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-3-oxo-5-(2-phenylethyl)octanoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 67.0h， 以75.1%的产率得到(6R)-4-hydroxy-3-[1-(3-nitrophenyl)-1-propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one
  参考文献：
  名称：

  A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690

  摘要：

  PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.

  DOI：

  10.1021/jo9809229

文献信息

• Synthesis of [¹⁴C] - and [¹³C₆]-labeled tipranavir and its potential hydroxyl metabolite and the glucuronide conjugate
  作者：Bachir Latli、Matt Hrapchak、John A. Easter、Wayne T. Stolle、Karl Grozinger、Dhileepkumar Krishnamurthy、Chris H. Senanayake

  DOI：10.1002/jlcr.1528

  日期：2008.7

  Tipranavir or Aptivus® is a non-peptidic protease inhibitor approved for the combination treatment with ritonavir of HIV infection. Tipranavir labeled with radioactive and stable isotopes of carbon was required for drug metabolism (excretion, distribution, and absorption) studies and to develop bioanalytical methods needed for the support of clinical studies. [7-14C]-Benzoic acid and uniformly labeled benzoic acid (ring-13C6 99 at% 13C) were used to prepare [14C]- and [13C6]-labeled tipranavir, respectively. Radioactively labeled tipranavir was prepared with a specific activity of 54 mCi/mmol (2GBq/mmol); it was necessary to dilute its specific activity with unlabeled tipranavir to 28 mCi/mmol (46.45 µCi/mg) because of its instability. The N-hydroxyl metabolite (12) and the glucuronide conjugate (13), the most abundant metabolites of tipranavir (when administered in conjunction with ritonavir) were also synthesized. Copyright © 2008 John Wiley & Sons, Ltd.

  替普瑞那韦或 Aptivus® 是一种非肽蛋白酶抑制剂，已被批准与利托那韦联合治疗艾滋病病毒感染。在进行药物代谢（排泄、分布和吸收）研究和开发支持临床研究所需的生物分析方法时，需要使用放射性和稳定碳同位素标记的替普瑞那韦。[7-14C]-苯甲酸和均匀标记的苯甲酸（环-13C6 99 at% 13C）分别用于制备[14C]-和[13C6]-标记的替拉那韦。放射性标记的替拉那韦的比活度为 54 mCi/mmol（2GBq/mmol）；由于其不稳定性，必须用未标记的替拉那韦将其比活度稀释至 28 mCi/mmol（46.45 µCi/mg）。此外，还合成了替拉那韦最丰富的代谢物 N- 羟基代谢物 (12) 和葡萄糖醛酸结合物 (13)（与利托那韦同时服用时）。Copyright © 2008 John Wiley & Sons, Ltd. All Rights Reserved.
• [DE] ENANTIOSELEKTIVE HYDRIERUNG VON INTERMEDIATEN BEI DER TIPRANAVIR-SYNTHESE<br/>[EN] ENANTIOSELECTIVE HYDROGENATION OF INTERMEDIATES DURING TIPRANAVIR SYNTHESIS<br/>[FR] HYDROGENATION ENANTIOSELECTIVE DE PRODUITS INTERMEDIAIRES LORS DE LA SYNTHESE DE TIPRANAVIR
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004085427A1

  公开（公告）日：2004-10-07

  Die Erfindung betrifft ein Verfahren zur Herstellung der Verbindungen der allgemeinen Formel (I) durch enantioselektive Hydrierung der Verbindungen der Formel (II) in Gegenwart von speziellen Hydrierungskatalysatoren. Die Erfindung zeichnet sich durch eine hohe Enantioselektivität aus, wodurch der einfache Zugang zu einer Substanzklasse wichtiger Arzneimittel möglich wird.

  该发明涉及一种通过手性选择性加氢在特定加氢催化剂的存在下制备一般式(I)化合物的方法，其中化合物的式子为(II)。该发明具有高度的手性选择性，从而可以简单地获得重要药物的一类物质。
• 2,5-Dimethyl-3,4-bis[(2<i>R</i>,5<i>R</i>)-2,5-dimethylphospholano]thiophene:  First Member of the Hetero-DuPHOS Family
  作者：Tiziana Benincori、Tullio Pilati、Simona Rizzo、Franco Sannicolò、Mark J. Burk、Lorenzo de Ferra、Elio Ullucci、Oreste Piccolo

  DOI：10.1021/jo050390d

  日期：2005.7.1

  The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholanolthiophene (UluPHOS), a new thiophene-based analogue of (RR)-1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically and electronically characterized, and employed as ligand of Rh and Ru in some standard hydrogenation reactions of prostereogenic functionalized carbon-carbon and carbon-oxygen double bonds. The synthesis of UlluPHOS is much easier than that provided for Me-DuPHOS. UlluPHOS and Me-DuPHOS display very similar geometries, while the electronic availability of the former is higher than that exhibited by the latter. The Rh and Ru complexes of UIluPHOS produced excellent enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-alpha-enamino acids and reaction rates higher than those found when employing the analogous complexes of Me-DuPHOS.
• J. Org. Chem. 1998, 63, 7348-7356
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1998, 41, 3467-3476
  作者：

  DOI：——

  日期：——