BOCPheΨProOMe | 118447-06-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: BOCPheΨProOMe
• 英文别名: Boc-Phe-ψ[CH2NH]Pro-OMe；methyl (2S)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl]pyrrolidine-2-carboxylate
• CAS: 118447-06-6
• 化学式: C₂₀H₃₀N₂O₄
• 分子量: 362.469
• InChiKey: VQGKVZCHRIQBIX-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  BOCPheΨProOMe 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 LeuPheΨProIle
  参考文献：
  名称：

  Development of methodology for the synthesis of stereochemically pure Phe.psi.[CH2N]Pro linkages in HIV protease inhibitors

  摘要：

  One of the strategies currently being pursued for the design of potential HIV protease inhibitors involves the replacement of the cleaved amide bond in a minimum peptide substrate with an aminomethylene unit. A commonly used method for the synthesis of these compounds involves a reductive alkylation of an amine with an aldehyde in the presence of sodium cyanoborohydride under acidic conditions. Accordingly, BOC-phenylalaninal (4) was reacted with the peptide-resin ProIleSer(OBzl)OResin (5) in the presence of acetic acid and sodium cyanoborohydride. The resulting product was found to consist of a mixture of diastereomers, which may result from the fact that the proline residue, which contains a secondary amine, reacts with the aldehyde to form an enamine 9 with loss of chirality at the modified Phe residue. Subsequent reduction of the iminium ion 10 would then result in production of the observed two diastereomers. In order to circumvent this problem, BOCPheProOBzl (12b) was synthesized and the central amide bond was reduced selectively with diborane. Hydrogenolysis of the benzyl protecting group gave BOCPhe-PSI[CH2N]Pro (14a), which was coupled manually to the peptide resin IleSer(OBzl)OResin to give BOCPhe-PSI[CH2N]ProIleSer(OBzl)OResin (6). Subsequent addition of amino acid residues to 6 and cleavage from the resin gave a series of stereochemically defined potential HIV protease inhibitors as single diastereomers. The most potent of these substances was ThrLeuAsnPhe-PSI[CH2N]ProIleSer (1), which displayed an IC50 of 1.1-mu-g/mL (1.4-mu-M) when tested for inhibition of HIV-1 protease. However, the epimer of 1 having the opposite configuration at the reduced Phe residue was inactive. A minimum length of seven amino acid residues appears to be necessary for effective recognition of the inhibitor by the enzyme. Further increase in chain length did not result in greater inhibitory potency.

  DOI：

  10.1021/jo00013a017
• 作为产物：
  描述：

  L-脯氨酸甲酯盐酸盐 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 diborane(6) 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 27.0h， 生成 BOCPheΨProOMe
  参考文献：
  名称：

  Development of methodology for the synthesis of stereochemically pure Phe.psi.[CH2N]Pro linkages in HIV protease inhibitors

  摘要：

  One of the strategies currently being pursued for the design of potential HIV protease inhibitors involves the replacement of the cleaved amide bond in a minimum peptide substrate with an aminomethylene unit. A commonly used method for the synthesis of these compounds involves a reductive alkylation of an amine with an aldehyde in the presence of sodium cyanoborohydride under acidic conditions. Accordingly, BOC-phenylalaninal (4) was reacted with the peptide-resin ProIleSer(OBzl)OResin (5) in the presence of acetic acid and sodium cyanoborohydride. The resulting product was found to consist of a mixture of diastereomers, which may result from the fact that the proline residue, which contains a secondary amine, reacts with the aldehyde to form an enamine 9 with loss of chirality at the modified Phe residue. Subsequent reduction of the iminium ion 10 would then result in production of the observed two diastereomers. In order to circumvent this problem, BOCPheProOBzl (12b) was synthesized and the central amide bond was reduced selectively with diborane. Hydrogenolysis of the benzyl protecting group gave BOCPhe-PSI[CH2N]Pro (14a), which was coupled manually to the peptide resin IleSer(OBzl)OResin to give BOCPhe-PSI[CH2N]ProIleSer(OBzl)OResin (6). Subsequent addition of amino acid residues to 6 and cleavage from the resin gave a series of stereochemically defined potential HIV protease inhibitors as single diastereomers. The most potent of these substances was ThrLeuAsnPhe-PSI[CH2N]ProIleSer (1), which displayed an IC50 of 1.1-mu-g/mL (1.4-mu-M) when tested for inhibition of HIV-1 protease. However, the epimer of 1 having the opposite configuration at the reduced Phe residue was inactive. A minimum length of seven amino acid residues appears to be necessary for effective recognition of the inhibitor by the enzyme. Further increase in chain length did not result in greater inhibitory potency.

  DOI：

  10.1021/jo00013a017

文献信息

• Novel aminomethylene-peptides as immunosuppressants
  申请人：Bayer Corporation

  公开号：EP0610743A1

  公开（公告）日：1994-08-17

  Compounds which suppress human T-lymphocyte proliferation are disclosed. The active compounds essentially contain at least the following structure:

  本发明公开了抑制人类 T 淋巴细胞增殖的化合物。活性化合物基本上至少包含以下结构：
• Novel route in the synthesis of ψ[CH2NH] amide bond surrogate
  作者：Pietro Campiglia、Claudio Aquino、Alessia Bertamino、Marina Sala、Isabel M. Gomez-Monterrey、Ettore Novellino、Paolo Grieco

  DOI：10.1016/j.tetlet.2007.11.112

  日期：2008.1

  An alternative method for the synthesis of pseudopeptides containing a psi[CH2NH] amide bond surrogate is reported. The synthetic approach is based on a nucleophilic displacement of the chiral N-protected beta-iodoamines with conveniently protected amino acid esters. The compatibility of this method with both conventional and microwave-assisted peptide synthesis should increase the potentiality of the psi[CH2NH] peptide bond isostere in peptide chemistry. (c) 2007 Elsevier Ltd. All rights reserved.
• CUSHMAN, MARK;OH, YOUNG-IM;COPELAND, TERRY D.;OROSZLAN, STEPHEN;SNYDER, S+, J. ORG. CHEM., 56,(1991) N3, C. 4161-4167
  作者：CUSHMAN, MARK、OH, YOUNG-IM、COPELAND, TERRY D.、OROSZLAN, STEPHEN、SNYDER, S+

  DOI：——

  日期：——
• Aminomethylene-peptides as immunosuppressants
  申请人：Bayer Corporation

  公开号：EP0610743B1

  公开（公告）日：1998-09-09
• Development of methodology for the synthesis of stereochemically pure Phe.psi.[CH2N]Pro linkages in HIV protease inhibitors
  作者：Mark Cushman、Young Im Oh、Terry D. Copeland、Stephen Oroszlan、Stuart W. Snyder

  DOI：10.1021/jo00013a017

  日期：1991.6

  One of the strategies currently being pursued for the design of potential HIV protease inhibitors involves the replacement of the cleaved amide bond in a minimum peptide substrate with an aminomethylene unit. A commonly used method for the synthesis of these compounds involves a reductive alkylation of an amine with an aldehyde in the presence of sodium cyanoborohydride under acidic conditions. Accordingly, BOC-phenylalaninal (4) was reacted with the peptide-resin ProIleSer(OBzl)OResin (5) in the presence of acetic acid and sodium cyanoborohydride. The resulting product was found to consist of a mixture of diastereomers, which may result from the fact that the proline residue, which contains a secondary amine, reacts with the aldehyde to form an enamine 9 with loss of chirality at the modified Phe residue. Subsequent reduction of the iminium ion 10 would then result in production of the observed two diastereomers. In order to circumvent this problem, BOCPheProOBzl (12b) was synthesized and the central amide bond was reduced selectively with diborane. Hydrogenolysis of the benzyl protecting group gave BOCPhe-PSI[CH2N]Pro (14a), which was coupled manually to the peptide resin IleSer(OBzl)OResin to give BOCPhe-PSI[CH2N]ProIleSer(OBzl)OResin (6). Subsequent addition of amino acid residues to 6 and cleavage from the resin gave a series of stereochemically defined potential HIV protease inhibitors as single diastereomers. The most potent of these substances was ThrLeuAsnPhe-PSI[CH2N]ProIleSer (1), which displayed an IC50 of 1.1-mu-g/mL (1.4-mu-M) when tested for inhibition of HIV-1 protease. However, the epimer of 1 having the opposite configuration at the reduced Phe residue was inactive. A minimum length of seven amino acid residues appears to be necessary for effective recognition of the inhibitor by the enzyme. Further increase in chain length did not result in greater inhibitory potency.