BOCPheΨProOH | 124869-91-6

• 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: BOCPheΨProOH
• 英文别名: BOCPheΨ(CH2N)ProOH；(2S)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl]pyrrolidine-2-carboxylic acid
• CAS: 124869-91-6
• 化学式: C₁₉H₂₈N₂O₄
• 分子量: 348.442
• InChiKey: CGIJFPZVQCRPSQ-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  BOCPheΨProOH 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以12.5 mg的产率得到PheΨProOH
  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-脯氨酸苄酯盐酸盐 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 diborane(6) 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 28.5h， 生成 BOCPheΨProOH
  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

• Retroviral protease binding peptides
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0352000A2

  公开（公告）日：1990-01-24

  Peptide mimics of the retrovirus protease polyprotein substrate bind to viral proteases and are useful in assaying for protease activity or inhibiting protease activity and in treating viral disease.

  逆转录病毒蛋白酶多聚蛋白底物的多肽模拟物与病毒蛋白酶结合，可用于检测蛋白酶活性或抑制蛋白酶活性以及治疗病毒性疾病。
• 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：——
• [EN] RETROVIRAL PROTEASE BINDING PEPTIDES
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：WO1990000399A1

  公开（公告）日：1990-01-25

  (EN) Peptide mimics of the retrovirus protease polyprotein substrate bind to viral proteases and are useful in assaying for protease activity or inhibiting protease activity and in treating viral disease.(FR) Des mimes peptidiques du substrat de polyprotéine de protéase de rétrovirus se lient à des protéases virales et sont utiles pour déterminer l'activité de la protéase ou pour inhiber son activité et dans le traitement de maladies virales.
• 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.