N-tert-butoxycarbonyl-(2S,4R)-4-methoxyprolylglycine benzyl ester | 1178549-19-3

• 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: N-tert-butoxycarbonyl-(2S,4R)-4-methoxyprolylglycine benzyl ester
• 英文别名: tert-butyl (2S,4R)-4-methoxy-2-[(2-oxo-2-phenylmethoxyethyl)carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1178549-19-3
• 化学式: C₂₀H₂₈N₂O₆
• 分子量: 392.452
• InChiKey: HTHBBDZFOHOIBU-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-(2S,4R)-4-methoxyprolylglycine benzyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues

  摘要：

  Collagen is the most abundant protein in animals, including humans. The prevalent (2S,4R)-4-hydroxyproline (Hyp) residues of collagen are known to confer great stability upon its triple-helical conformation. The basis for that stability has been attributed to hydration of the pendant hydroxyl groups. Here, that attribution is shown to be incorrect. Replacement of the natural Hyp residues with synthetic (2S,4R)-4-methoxyproline (Mop) residues is shown by circular dichronism spectroscopy and differential scanning calorimetry to increase the conformational stability of the collagen triple helix. The thermodynamic parameters indicate that, as expected, O-methylation decreases the hydration of the triple helix. Apparently, hydration of Hyp residues is deleterious, rather than advantageous, to the collagen triple helix. The crystal structure of Ac-Mop-OMe reveals the manifestation of two stereoelectronic effects: a gauche effect and an n -> infinity* interaction, which preorganize the main-chain atoms properly for triple helix formation. Thus, the conformational stability conferred upon the collagen triple helix by O-methylation provides strong evidence that the hydroxyl group of Hyp acts primarily through stereoelectronic effects and that is hydration provides no benefit. This information could have practical utility, as Mop could be prepared in situ by the O-methylation of Hyp residues in natural collagen. Such a semisynthetic collagen could have superior properties as a biomaterial.

  DOI：

  10.1021/ja800225k
• 作为产物：
  描述：

  甘氨酸苄酯对甲苯磺酸盐 、 (2S,4R)-1-(叔丁氧羰基)-4-甲氧基吡咯烷-2-羧酸 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以82%的产率得到N-tert-butoxycarbonyl-(2S,4R)-4-methoxyprolylglycine benzyl ester
  参考文献：
  名称：

  Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues

  摘要：

  Collagen is the most abundant protein in animals, including humans. The prevalent (2S,4R)-4-hydroxyproline (Hyp) residues of collagen are known to confer great stability upon its triple-helical conformation. The basis for that stability has been attributed to hydration of the pendant hydroxyl groups. Here, that attribution is shown to be incorrect. Replacement of the natural Hyp residues with synthetic (2S,4R)-4-methoxyproline (Mop) residues is shown by circular dichronism spectroscopy and differential scanning calorimetry to increase the conformational stability of the collagen triple helix. The thermodynamic parameters indicate that, as expected, O-methylation decreases the hydration of the triple helix. Apparently, hydration of Hyp residues is deleterious, rather than advantageous, to the collagen triple helix. The crystal structure of Ac-Mop-OMe reveals the manifestation of two stereoelectronic effects: a gauche effect and an n -> infinity* interaction, which preorganize the main-chain atoms properly for triple helix formation. Thus, the conformational stability conferred upon the collagen triple helix by O-methylation provides strong evidence that the hydroxyl group of Hyp acts primarily through stereoelectronic effects and that is hydration provides no benefit. This information could have practical utility, as Mop could be prepared in situ by the O-methylation of Hyp residues in natural collagen. Such a semisynthetic collagen could have superior properties as a biomaterial.

  DOI：

  10.1021/ja800225k

文献信息

• STABILIZATION OF THE COLLAGEN TRIPLE HELIX BY O-METHYLATION OF HYDROXYPROLINE RESIDUES
  申请人：Raines Ronald T.

  公开号：US20090264626A1

  公开（公告）日：2009-10-22

  This invention relates to a collagen polypeptide comprising a tripeptide motif having the formula (ProYaaGly) n , where Yaa is an O-methylated amino acid residue and “n” is the number of motif repeats. Preferred O-methylated amino acid residues at the Yaa position include (2S,4R)-4-methoxyproline. Other suitable amino acid residues at that position include O-mono or O-di-halogenated methylproline. Also, disclosed is a method of making a synthetic or a semi-synthetic collagen polypeptide molecule having increased stability relative to natural collagen. The strengthened collagen molecules are suitable for use in biomaterials for the medical field or in leather-related products prepared by the tanning industry.

  本发明涉及一种胶原蛋白多肽，其包含具有公式（ProYaaGly）n的三肽基序，其中Yaa是O-甲基化的氨基酸残基，“n”是基序重复的次数。在Yaa位置的首选O-甲基化氨基酸残基包括（2S，4R）-4-甲氧基脯氨酸。该位置上的其他适当氨基酸残基包括O-单或O-双卤代甲基脯氨酸。此外，还揭示了一种制备具有相对于天然胶原蛋白增强稳定性的合成或半合成胶原蛋白分子的方法。强化的胶原分子适用于医学领域的生物材料或由制革工业制备的皮革相关产品。
• US7858741B2
  申请人：——

  公开号：US7858741B2

  公开（公告）日：2010-12-28
• Stabilization of the Collagen Triple Helix by <i>O</i>-Methylation of Hydroxyproline Residues
  作者：Frank W. Kotch、Ilia A. Guzei、Ronald T. Raines

  DOI：10.1021/ja800225k

  日期：2008.3.1

  Collagen is the most abundant protein in animals, including humans. The prevalent (2S,4R)-4-hydroxyproline (Hyp) residues of collagen are known to confer great stability upon its triple-helical conformation. The basis for that stability has been attributed to hydration of the pendant hydroxyl groups. Here, that attribution is shown to be incorrect. Replacement of the natural Hyp residues with synthetic (2S,4R)-4-methoxyproline (Mop) residues is shown by circular dichronism spectroscopy and differential scanning calorimetry to increase the conformational stability of the collagen triple helix. The thermodynamic parameters indicate that, as expected, O-methylation decreases the hydration of the triple helix. Apparently, hydration of Hyp residues is deleterious, rather than advantageous, to the collagen triple helix. The crystal structure of Ac-Mop-OMe reveals the manifestation of two stereoelectronic effects: a gauche effect and an n -> infinity* interaction, which preorganize the main-chain atoms properly for triple helix formation. Thus, the conformational stability conferred upon the collagen triple helix by O-methylation provides strong evidence that the hydroxyl group of Hyp acts primarily through stereoelectronic effects and that is hydration provides no benefit. This information could have practical utility, as Mop could be prepared in situ by the O-methylation of Hyp residues in natural collagen. Such a semisynthetic collagen could have superior properties as a biomaterial.