(2S,3R)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane | 161282-72-0

• 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: (2S,3R)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane
• 英文别名: (2R,3S)-3-tert-butoxycarbonylamino-1-nitro-4-phenyl-2-butanol；tert-butyl ((2S,3R)-3-hydroxy-4-nitro-1-phenylbutan-2-yl)carbamate；tert-butyl N-[(2S,3R)-3-hydroxy-4-nitro-1-phenylbutan-2-yl]carbamate
• CAS: 161282-72-0
• 化学式: C₁₅H₂₂N₂O₅
• 分子量: 310.35
• InChiKey: WAEZXLPMZDLZJT-QWHCGFSZSA-N

物化性质

• 沸点：
  505.2±50.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane 在 platinum(IV) oxide 、 镍 氢气 作用下， 以 甲醇 为溶剂， 25.0~35.0 ℃ 、4.05 MPa 条件下， 反应 19.0h， 生成 [(1S,2R)-2-羟基-3-[(2-甲基丙基)氨基]-1-(苯基甲基)丙基]-1,1,-二甲基乙酯
  参考文献：
  名称：

  A Facile Synthesis of (2R3S)-1-Amino-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutane;A Useful Component Block of HIV Protease Inhibitor

  摘要：

  (S)-3-tert-Butoxycarbonylamino-1-nitro-2-oxo-4-phenylbutane 4 was converted to (2R,3S)-1-amino-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutane 5a by a catalytic hydrogenation, or NaBH(4)-TiCl(4) reduction followed by hydrogenation in favorable diastereoselectivity, a component of the HIV protease inhibitor VX-478.

  DOI：

  10.1080/00397919808005092
• 作为产物：
  描述：

  (S)-phenyl 2-((tert-butoxycarbonyl)amino)-3-phenylpropanoate 在 potassium tert-butylate 、 aluminum tri-tert-butoxide 作用下， 以 二甲基亚砜 、 异丙醇 为溶剂， 反应 3.0h， 生成 (2S,3R)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane
  参考文献：
  名称：

  达芦那韦中间体的合成新工艺

  摘要：

  一种达芦那韦中间体的合成新工艺：以N‑叔丁氧羰基‑L‑苯丙氨酸为原料，通过酯化，缩合，还原，氢化，还原胺化等反应制备达芦那韦关键中间体(2R,3S)‑3‑叔丁氧羰基氨基1‑[(2‑甲基丙基)氨基]‑4‑苯基2‑丁醇。该合成新工艺反应条件温和，操作简便，反应选择性和收率高，更适宜工业化生产。

  公开号：

  CN105085323B

文献信息

• Diastereoselective catalytic asymmetric nitroaldol reaction utilizing rare earth-Li-(R)-BINOL complex. A highly efficient synthesis of norstatine
  作者：Hiroaki Sasai、Won-Sup Kim、Takeyuki Suzuki、Masakatsu Shibasaki、Masaru Mitsuda、Junzo Hasegawa、Takehisa Ohashi

  DOI：10.1016/0040-4039(94)88093-x

  日期：1994.8

  Rare earth-Li-BINOL complexes were used to catalyze nitroaldol reactions of optically active α-amino-aldehydes with nitromethane in a highly diastereoselective manner. A typical adduct, (2S, 3S)-3-phthaloylamino-2-hydroxy-1-nitro-4-phenylbutane was conveniently converted to (2S, 3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (erythro-AHPA ; phenylnorstatine), a component of the HIV protease inhibitor

  稀土-Li-BINOL络合物用于以高度非对映选择性的方式催化旋光性α-氨基醛与硝基甲烷的硝基羟醛反应。典型的加合物（2 S，3 S）-3-邻苯二甲酰基氨基-2-羟基-1-硝基-4-苯基丁烷可方便地转化为（2 S，3 S）-3-氨基-2-羟基-4-苯基丁酸酸（赤型-AHPA；苯基去甲他汀），是HIV蛋白酶抑制剂KNI-227和KNI-272的成分。
• Stereoselective Synthesis of the Key Intermediates of the HIV Protease Inhibitor Fosamprenavir and Its Diastereomer
  作者：Miloš Sedlák、Illia Panov、Pavel Drabina、Jiří Hanusek

  DOI：10.1055/s-0033-1338803

  日期：——

  Highly stereoselective Henry reaction has been used in the synthesis of the fosamprenavir precursor (2 S ,3 R )- N - tert- butyl­oxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane and its 2 S ,3 S diasteromer from N-tert- butyloxycarbonyl-( S )-phenylalaninal and nitromethane. The complex of (2 S ,5 R )- or (2 R ,5 S )-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one with copper(II) acetate

  高度立体选择性亨利反应已用于合成福沙那韦前体 (2 S ,3 R )-N-叔丁氧羰基-2-氨基-3-羟基-1-苯基-4-硝基丁烷及其 2 S ,3 S N-叔丁氧羰基-(S)-苯丙醛和硝基甲烷的非对映异构体。(2 S ,5 R )-或(2 R ,5 S )-5-异丙基-5-甲基-2-(吡啶-2-基)咪唑烷-4-酮与乙酸铜(II)的络合物已得到用作催化剂，分别为产物提供 2 S ,3 R 绝对构型（dr = 90:10，总收率 89%）或 2 S,3 S（dr = 99:1，总收率 94%）。
• Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold
  作者：Claire-Lise Ciana、Romain Siegrist、Hamed Aissaoui、Léo Marx、Sophie Racine、Solange Meyer、Christoph Binkert、Ruben de Kanter、Christoph Fischli、Sergio Wittlin、Christoph Boss

  DOI：10.1016/j.bmcl.2012.11.118

  日期：2013.2

  A novel series of anti-malarials, based on a hydroxy-ethyl-amine scaffold, initially identified as peptidomimetic protease inhibitors is described. Combination of the hydroxy-ethyl-amine anti-malarial phramacophore with the known Mannich base pharmacophore of amodiaquine (57) resulted in promising in vivo active novel derivatives. (c) 2012 Elsevier Ltd. All rights reserved.
• re- andsi-Face-Selective Nitroaldol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt: A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478)
  作者：E. J. Corey、Fu-Yao Zhang

  DOI：10.1002/(sici)1521-3773(19990712)38:13/14<1931::aid-anie1931>3.0.co;2-4

  日期：1999.7.12

  Either amprenavir (1) or its C(2) diastereomer can be synthesized in a simple way by the use of a nitroaldol reaction carried out in the presence of one or the other of the two ammonium ions 2. The 1,3-diamino-2-hydroxypropyl structural element of 1 is also found in many other peptidomimetics and HIV protease inhibitors. Described here is a new strategy for possible application to direct and stereocontrolled synthesis of such compounds.
• [EN] PROCESS FOR STEREOSELECTIVE PREPARATION OF AN INTERMEDIATE OF PROTEASE INHIBITORS<br/>[FR] PROCÉDÉ DE PRÉPARATION STÉRÉOSÉLECTIVE D'UN INTERMÉDIAIRE D'INHIBITEURS DE PROTÉASES
  申请人：PIRAMAL HEALTHCARE LTD

  公开号：WO2010143150A2

  公开（公告）日：2010-12-16

  The present invention provides a process for stereoselective preparation of N-[(1S,2R)-2- hydroxy-3-nitro-l-(phenylmethyl)propyl]carbamic acid 1,1-dimethylethyl ester (nitroalcohol) comprising asymmetric reduction of the carbonyl group in [(1S)-3-nitro-2- oxo-1-(phenylmethyl)propyl]carbamic acid 1,1-dimethylethyl ester (nitroketone) using sodium borohydride as the reducing agent in a solvent mixture of an alcohol and a halogenated solvent at a temperature ranging from -15°C to 00C to yield nitroalcohol in > 78 % yield and > 99 % chiral purity.