benzyl (S)-3-{[(tert-butoxy)carbonyl]amino}-4-phenylbutanoate | 329348-45-0

• 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: benzyl (S)-3-{[(tert-butoxy)carbonyl]amino}-4-phenylbutanoate
• 英文别名: (3S)-N-(Boc)-β-homophenylalanine benzyl ester；Boc-(S)-β³-HPhe-OBn；Boc-β³-HPhe-OBn；benzyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutanoate
• CAS: 329348-45-0
• 化学式: C₂₂H₂₇NO₄
• 分子量: 369.461
• InChiKey: AOOZKWKJVJUPKF-IBGZPJMESA-N

物化性质

• 沸点：
  511.2±50.0 °C(Predicted)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (S)-3-{[(tert-butoxy)carbonyl]amino}-4-phenylbutanoate 在 N-甲基吗啉 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.25h， 生成 benzyl (3S)-4-phenyl-3-[[(2S)-2-[[(2S)-1-[[(2-phenylacetyl)amino]-prop-2-ynylcarbamoyl]pyrrolidine-2-carbonyl]amino]-3-pyridin-3-ylpropanoyl]amino]butanoate
  参考文献：
  名称：

  Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics

  摘要：

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.

  DOI：

  10.1021/jm200608k
• 作为产物：
  描述：

  (3S)-tert-butyl 1-benzyl-3-diazo-2-oxopropylcarbamate 、 苯甲醇 在 silver benzoate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以70%的产率得到benzyl (S)-3-{[(tert-butoxy)carbonyl]amino}-4-phenylbutanoate
  参考文献：
  名称：

  具有七个功能化侧链的α-十二肽的固相合成和 CD 光谱证据表明从水到甲醇溶液时发生显着的结构转换

  摘要：

  应用 Fmoc 方法和 Wang 树脂，通过手动固相技术合成了数毫克的全β3-十二肽，具有受保护的 N 端硫醇锚定基团和七个侧链。序列为β-HLys-β-HPhe-β-HTyr-β-HLeu-β-HLys-β-HSer-β-HLys-β-HPhe-β-HSer-β-HVal-β-HLys-β-HAla -OH（从 N 端到 C 端；见 1）。结构单元侧链中的官能团被 Boc (β-HLys) 或 t-Bu 醚 (β-HSer, β-HTyr) 保护，以允许用三氟乙酸同时脱保护和从树脂上脱离。所有偶联步骤均使用 HBTU（=O-（1H-苯并三唑-1-基）-1,1,3,3-四甲基脲六氟磷酸盐）/HOBt（=1-羟基-1H-苯并三唑）在 DMF 中实现。对于 Fmoc (=(9H-fluoren-9-yl)methoxycarbonyl) 脱保护，当链长超过七个或八个氨基酸部分时，开发了一种方案以克服先前报道的

  DOI：

  10.1002/1522-2675(20001220)83:12<3139::aid-hlca3139>3.0.co;2-w

文献信息

• Solid-Phase Synthesis of aβ-Dodecapeptide with Seven Functionalized Side Chains and CD-Spectroscopic Evidence for a Dramatic Structural Switch When Going from Water to Methanol Solution
  作者：Jürg V. Schreiber、Dieter Seebach

  DOI：10.1002/1522-2675(20001220)83:12<3139::aid-hlca3139>3.0.co;2-w

  日期：2000.12.20

  missing in the CD spectrum, only a strong positive Cotton effect at 202 nm was observed, indicating the presence of β-peptidic secondary structures, containing ten-membered H-bonded rings, such as the 12/10 helix (Fig. 4, right) or the hairpin. Only a detailed NMR solution-structure analysis will provide the clues necessary for understanding the effects leading to the observed dramatic structural change of

  应用 Fmoc 方法和 Wang 树脂，通过手动固相技术合成了数毫克的全β3-十二肽，具有受保护的 N 端硫醇锚定基团和七个侧链。序列为β-HLys-β-HPhe-β-HTyr-β-HLeu-β-HLys-β-HSer-β-HLys-β-HPhe-β-HSer-β-HVal-β-HLys-β-HAla -OH（从 N 端到 C 端；见 1）。结构单元侧链中的官能团被 Boc (β-HLys) 或 t-Bu 醚 (β-HSer, β-HTyr) 保护，以允许用三氟乙酸同时脱保护和从树脂上脱离。所有偶联步骤均使用 HBTU（=O-（1H-苯并三唑-1-基）-1,1,3,3-四甲基脲六氟磷酸盐）/HOBt（=1-羟基-1H-苯并三唑）在 DMF 中实现。对于 Fmoc (=(9H-fluoren-9-yl)methoxycarbonyl) 脱保护，当链长超过七个或八个氨基酸部分时，开发了一种方案以克服先前报道的
• Syntheses and CD-Spectroscopic Investigations of Longer-Chain -Peptides: Preparation by Solid-Phase Couplings of Single Amino Acids, Dipeptides, and Tripeptides
  作者：Per I. Arvidsson、Jens Frackenpohl、Dieter Seebach

  DOI：10.1002/hlca.200390133

  日期：2003.5

  for the efficient syntheses of longer-chain β-peptides (>9 residues) were investigated. They were synthesized on solid phase with Fmoc-protected amino acids or Fmoc-protected di- or tripeptide fragments (assembled using solution-phase synthesis). The use of preformed fragments significantly increased the purity of the crude peptides and facilitated purification. Especially, the use of Fmoc-protected

  11水溶性的合成和CD-光谱分析β -肽组成清一色的β 3或交替β 2 -和β 3 -氨基酸进行说明。研究了有效合成长链β肽（> 9个残基）的不同方法。它们在固相上与Fmoc保护的氨基酸或Fmoc保护的二肽或三肽片段合成（使用溶液相合成法组装）。使用预先形成的片段可显着提高粗肽的纯度并促进纯化。特别是，使用Fmoc保护的β 2 / β 3-dipeptides用于合成一个“混合” β 2 / β 3 -nonapeptide被证明是非常有效的，得到粗肽纯度在95％和不具有可检测的差向异构化β 2 -氨基酸残基。这是对先前报道的β-肽固相合成方法的一项重大改进，并预示着β-肽研究领域将由合成转向复杂功能性“ β-蛋白”的设计和研究。
• Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics
  作者：Carine B. Bourguet、Eugénie Goupil、Danaë Tassy、Xin Hou、Eryk Thouin、Felix Polyak、Terence E. Hébert、Audrey Claing、Stéphane A. Laporte、Sylvain Chemtob、William D. Lubell

  DOI：10.1021/jm200608k

  日期：2011.9.8

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.