(2R,4R,5S)-2-Benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acid | 98818-43-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2R,4R,5S)-2-Benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acid
• 英文别名: (2R,4R,5S)-2-benzyl-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid
• CAS: 98818-43-0
• 化学式: C₂₄H₃₁NO₅
• 分子量: 413.514
• InChiKey: VYDYYZDALYHNLP-QHAWAJNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4R,5S)-2-Benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acid 在 咪唑 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2R-benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6-phenyl-hexanoic acid
  参考文献：
  名称：

  Short Total Synthesis of Aspartyl Protease Inhibitors L-685,434, L-682,679 and L-685,458

  摘要：

  羟乙基二肽等效体L-685,434、L-682,679和L-685,458通过一系列步骤合成，包括与烯丙基三氯锡烷的偶联反应生成α-氨基醛，随后对相应的1,2-顺式和1,2-反式氨基醇进行硼氢化反应生成二醇，在TPAP条件下内酯化，内酯开环并与所需胺或二肽酰胺进行肽偶联反应。

  DOI：

  10.1055/s-2002-34891
• 作为产物：
  描述：

  苯丙醛,a-[二(苯基甲基)氨基]-,(S)- 在 palladium dihydroxide lithium hydroxide 、 三甲基氯硅烷 、 氢气 、 氯化铵 、 对甲苯磺酸 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 甲苯 为溶剂， -78.0~25.0 ℃ 、344.73 kPa 条件下， 反应 18.0h， 生成 (2R,4R,5S)-2-Benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acid
  参考文献：
  名称：

  Zinc-Mediated Allylation of N-Protected α-Amino Aldehydes in Aqueous Solution. Stereoselective Synthesis of Phe-Phe Hydroxyethylene Dipeptide Isosteres

  摘要：

  开发了一条高效的合成Phe-Phe羟基乙烯二肽异构体的路线，用于设计潜在的肾素和HIV蛋白酶抑制剂。

  DOI：

  10.1055/s-1997-803

文献信息

• Allyltrichlorostannane Additions to α-Amino Aldehydes: Application to the Total Synthesis of the Aspartyl Protease Inhibitors<scp>l</scp>-682,679,<scp>l</scp>-684,414,<scp>l</scp>-685,434, and<scp>l</scp>-685,458
  作者：Luiz C. Dias、Gaspar Diaz、Andrea A. Ferreira、Paulo R. Meira、Edílson Ferreira

  DOI：10.1055/s-2003-37649

  日期：——

  The hydroxyethylene dipeptide isosteres l-682,679, l-684,414, l-685,434, and l-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-syn and 1,2-anti amino alcohols to give the diols, lactonization under TPAP conditions, lactone opening, and peptide coupling with the desired amine or dipeptide amide. The present synthetic approach represents a practical entry to a large range of other dipeptide isosteres.

  羟基亚乙基二肽等排体l-682,679、l-684,414、l-685,434和l-685,458通过一系列步骤合成，包括与α-氨基醛的烯丙基三氯锡烷偶联、相应的1,2-顺式和1,2-反式氨基醇的氢硼化反应生成二醇、在TPAP条件下内酯化、内酯开环以及与所需胺或二肽酰胺的肽偶联。这种合成方法为其他大量二肽等排体的制备提供了一条实用的途径。
• 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。
• Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond. II. Preparation of Pseudotetrapeptides Derived from Diastereoisomeric 5-Amino-2-benzyl-4-hydroxy-6-phenylhexanoic Acids
  作者：Jaroslav Litera、Jan Weber、Ivana Křížová、Iva Pichová、Jan Konvalinka、Martin Fusek、Milan Souček

  DOI：10.1135/cccc19980541

  日期：——

  Twelve pseudotetrapeptides, Boc-NHCH(CH₂Ph)CH(OH)CH₂CH(CH₂Ph) CO-Xaa-Phe-NH₂ 9-11, were prepared by [(benzotriazol-1-yl)oxy]tris(dimethylamino)phosphonium hexafluorophosphate-mediated couplings of diastereoisomeric O-silylated (2R or 2S,4R or 4S,5S)-2-benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acids 1 with dipeptides H-Xaa-Phe-NH₂ (Xaa = Gln, Glu(OBzl) or Ile) 3-5, followed by O-deprotection. Pseudotetrapeptides 9-11 were tested for inhibition of aspartic proteinases secreted by Candida albicans and C. tropicalis. The level of inhibition of both yeast proteinases was very low, contrasting with the nanomolar IC₅₀ values obtained for inhibition of HIV-1 proteinase.

  十二种伪四肽Boc-NHCH(CH2Ph)CH(OH)CH2CH(CH2Ph)CO-Xaa-Phe-NH2（9-11）通过[(苯并三唑-1-基氧基)三(二甲基氨基)磷酸六氟磷酸盐]介导的偶联反应制备，反应物为对映异构的O-硅烷基化(2R或2S,4R或4S,5S)-2-苄基-5-(tert-丁氧羰基)氨基-4-羟基-6-苯基己酸1与二肽H-Xaa-Phe-NH2（Xaa = 谷氨酰谷氨酸、谷氨酸(OBzl)或异亮氨酸）（3-5），然后进行O-去保护。伪四肽9-11被用于抑制由白念珠菌和热带白念珠菌分泌的天冬氨酸蛋白酶。两种酵母蛋白酶的抑制水平非常低，与抑制HIV-1蛋白酶所获得的纳摩尔IC50值形成对比。
• 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。
• Development of clickable active site-directed photoaffinity probes for γ-secretase
  作者：Christina J. Crump、Christopher W. am Ende、T. Eric Ballard、Nikolay Pozdnyakov、Martin Pettersson、De-Ming Chau、Kelly R. Bales、Yue-Ming Li、Douglas S. Johnson

  DOI：10.1016/j.bmcl.2012.02.027

  日期：2012.4

  We have developed clickable active site-directed photoaffinity probes for gamma-secretase which incorporate a photoreactive benzophenone group and an alkyne handle for subsequent click chemistry mediated conjugation with azide-linked reporter tags for visualization (e.g., TAMRA-azide) or enrichment (e.g., biotinazide) of labeled proteins. Specifically, we synthesized clickable analogs of L646 (2) and L505 (3) and validated specific labeling to presenilin-1 N-terminal fragment (PS1-NTF), the active site aspartyl protease component within the gamma-secretase complex. Additionally, we were able to identify signal peptide peptidase (SPP) by Western blot analysis. Furthermore, we analyzed the photo-labeled proteins in an unbiased fashion by click chemistry with TAMRA-azide followed by in-gel fluorescence detection. This approach expands the utility of gamma-secretase inhibitor (GSI) photoaffinity probes in that labeled proteins can be tagged with any number of azide-linked reporters groups using a single clickable photoaffinity probe for target pull down and/or fluorescent imaging applications. (C) 2012 Elsevier Ltd. All rights reserved.