(2S,3S)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane | 174302-74-0

• 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,3S)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane
• 英文别名: tert-butyl ((2S,3S)-3-hydroxy-4-nitro-1-phenylbutan-2-yl) carbamate；tert-butyl N-[(2S,3S)-3-hydroxy-4-nitro-1-phenylbutan-2-yl]carbamate
• CAS: 174302-74-0
• 化学式: C₁₅H₂₂N₂O₅
• 分子量: 310.35
• InChiKey: WAEZXLPMZDLZJT-STQMWFEESA-N

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,3S)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 magnesium sulfate 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 叔-丁基((2S,3S)-3-羟基-4-(异丁基氨基)-1-苯基丁烷-2-基)氨基甲酯
  参考文献：
  名称：

  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)

  摘要：

  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.

  DOI：

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

  BOC-L-苯丙氨酸 在 sodium tetrahydroborate 、 potassium tert-butylate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 生成 (2S,3S)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane
  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

文献信息

• Formation of multi-stereogenic centers using a catalytic diastereoselective Henry reaction
  作者：Takayoshi Arai、Yoshinori Taneda、Yoko Endo

  DOI：10.1039/c0cc03022h

  日期：——

  A diastereoselective Henry reaction of chiral aldehydes with nitroalkanes was developed using a chiral sulfonyldiamine (L1)-CuCl complex. The reaction of (R)-2-phenylpropanal and nitromethane was smoothly catalyzed by the (S,S,S)-L1-CuCl complex to give the adduct with 99/1 syn/anti selectivity in 99% ee. In the reaction of (S)-2-phenylpropanal and nitroethane, the (R,R,R)-L1-CuCl catalyst yielded

  使用手性磺酰基二胺（L1）-CuCl配合物开发了手性醛与硝基烷烃的非对映选择性亨利反应。（R）-2-苯基丙醛与硝基甲烷的反应被（S，S，S）-L 1 -CuCl配合物平稳地催化，从而在99％ee中得到具有99/1顺/反选择性的加合物。在（S）-2-苯基丙醛和硝基乙烷的反应中，（R，R，R）-L1-CuCl催化剂在高度同位选择的亨利反应中产生了预期的三个连续的立体中心。
• 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.
• [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.