2R-benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6-phenyl-hexanoic acid | 98818-49-6

• 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-benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6-phenyl-hexanoic acid
• 英文别名: (2R,4R,5S)-2-benzyl-5-tert-butoxycarbonylamino-4-(tert-butyldimethylsilyloxy)-6-phenylhexanoic acid；(2R,4R,5S)-2-benzyl-4-[tert-butyl(dimethyl)silyl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid
• CAS: 98818-49-6
• 化学式: C₃₀H₄₅NO₅Si
• 分子量: 527.777
• InChiKey: UEVGWVOLUCPPDE-UODIDJSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.85
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2R-benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6-phenyl-hexanoic acid 在 N-甲基吗啉 、 四丁基氟化铵 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 {(1S,2R,4R)-1-Benzyl-4-[(1S,2S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-2-methyl-butylcarbamoyl]-2-hydroxy-5-phenyl-pentyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  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

  摘要：

  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。

  DOI：

  10.1135/cccc19980541
• 作为产物：
  描述：

  (2-benzylallyl)trichlorostannane 在 咪唑 、 lithium hydroxide 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 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

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。
• 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。
• Investigating γ-secretase protein interactions in live cells using active site-directed clickable dual-photoaffinity probes
  作者：T. Eric Ballard、Heather E. Murrey、Kieran F. Geoghegan、Christopher W. am Ende、Douglas S. Johnson

  DOI：10.1039/c3md00283g

  日期：——

  Clickable γ-secretase active site-directed dual-photoaffinity probes specifically label components of the γ-secretase complex and form crosslinks between PS1-NTF and PS1-CTF.

  可点击的γ-分泌酶活性位点定向双光致亲和探针能够特异性地标记γ-分泌酶复合物的组分，并在PS1-NTF和PS1-CTF之间形成交联。
• Development of CBAP-BPyne, a probe for γ-secretase and presenilinase
  作者：Natalya Gertsik、T. Eric Ballard、Christopher W. am Ende、Douglas S. Johnson、Yue-Ming Li

  DOI：10.1039/c3md00281k

  日期：——

  CBAP-BPyne, a dual presenilinase and γ-secretase clickable probe, provides a novel means to investigate the mechanism of endoproteolysis.

  CBAP-BPyne是一种双重的前突触酶和γ-分泌酶可点击探针，为研究内部蛋白酶解机制提供了一种新的手段。
• 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.