leucylproline tert-butyl ester | 74509-15-2

• 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: leucylproline tert-butyl ester
• 英文别名: tert-butyl (2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidine-2-carboxylate
• CAS: 74509-15-2
• 化学式: C₁₅H₂₈N₂O₃
• 分子量: 284.399
• InChiKey: YFZYRXDTTBGFBW-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  leucylproline tert-butyl ester 在 4 Angstroem MS 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (2S)-1-[(2S)-2-[[2-[(1S)-1-[[2-[2-[(1S)-1-amino-2-methylpropyl]-1,3-thiazol-4-yl]-5-methyl-1,3-oxazole-4-carbonyl]amino]ethyl]-1,3-oxazole-4-carbonyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  First Total Synthesis of Leucamide A

  摘要：

  The first total synthesis of marine bioactive cyclic heptapeptide Leucamide A has been accomplished, including a simple method for construction of the 4,2-bisheterocycle tandem pair substructure that employs a DAST-mediated cyclization of beta-hydroxy amide and final HBTU-promoted ring closing.

  DOI：

  10.1021/jo026799+
• 作为产物：
  描述：

  Fluorenylmethoxycarbonylleucyl-proline tert-butyl ester 在 二乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 leucylproline tert-butyl ester
  参考文献：
  名称：

  环状七肽axinastatin 2和axinastatin 3的合成

  摘要：

  通过对氨基酸和肽中间体的单元的N端采用Fmoc保护，对C端采用叔丁酯封闭，完成了抗乙酰抑制素2 2b和3 2c的实际全部合成。通常，已证明磷腈氰二乙基酯可有效地形成肽键，并且在一种例外情况下，天冬酰胺，邻硝基苯基活性酯被证明是有用的。对于最终的环化反应，发现BOP-Cl特别有效。

  DOI：

  10.1039/p19960002411

文献信息

• Synthesis of the cyclic heptapeptides axinastatin 2 and axinastatin 3
  作者：George R. Pettit、Jeffrey W. Holman、Gerard M. Boland

  DOI：10.1039/p19960002411

  日期：——

  Practical total syntheses of axinastatins 2 2b and 3 2c were completed by employing Fmoc protection for the N-terminal, and tert-butyl ester blocking for the C-terminal, units of the amino acid and peptide intermediates. Generally, diethyl phosphorocyanidate proved effective for formation of the peptide bond, and in the one exception, asparagine, the o-nitrophenyl active ester proved to be useful.

  通过对氨基酸和肽中间体的单元的N端采用Fmoc保护，对C端采用叔丁酯封闭，完成了抗乙酰抑制素2 2b和3 2c的实际全部合成。通常，已证明磷腈氰二乙基酯可有效地形成肽键，并且在一种例外情况下，天冬酰胺，邻硝基苯基活性酯被证明是有用的。对于最终的环化反应，发现BOP-Cl特别有效。
• Human chorionic gonadotropin. II. Synthesis of a hexadecapeptide corresponding to the C-terminal sequence 132-147 of the .BETA.-subunit of human chorionic gonadotropin (hCG).
  作者：KOICHI KAWASAKI、CHIYE KAWASAKI、YUKO TSUDA、MITSUKO MAEDA、YOSHIO OKADA、KENJI YAMAJI、TETSU TAKAGI、OSAMU TANIZAWA

  DOI：10.1248/cpb.28.2692

  日期：——

  A hexadecapeptide, H-Arg-Leu-Pro-Gly-Pro-Asn-Thr-Pro-Ile-Leu-Pro-Gln-Ser-Leu-Pro-OH, corresponding to the C-terminal sequence 132-147 of hCG-β proposed by Carlsen et al., was synthesized stepwise by fragment condensation, assembling five fragments [Z-Arg(NO2)-Leu-Pro-NHNHBoc, Z-Gly-Pro-Pro-NHNHBoc, Z-Asn-Thr-Pro-NHNHBoc, Z-Ile-Leu-Pro-NHNHBoc, and Z-Gln-Ser-Leu-Pro-OBut].

  通过片段缩合法逐步合成了 H-Arg-Leu-Pro-Gly-Pro-Asn-Thr-Pro-Ile-Leu-Pro-Gln-Ser-Leu-Pro-OH 六十肽，对应于 Carlsen 等人提出的 hCG-β C 端序列 132-147、通过片段缩合逐步合成了五个片段[Z-Arg(NO2)-Leu-Pro-NHNHBoc、Z-Gly-Pro-Pro-NHNHBoc、Z-Asn-Thr-Pro-NHNHBoc、Z-Ile-Leu-Pro-NHNHBoc 和 Z-Gln-Ser-Leu-Pro-OBut]。
• pH Dependence of inhibitors targeting the occluding loop of cathepsin B
  作者：Brian E Cathers、Cynthia Barrett、James T Palmer、Robert M Rydzewski

  DOI：10.1016/s0045-2068(02)00009-3

  日期：2002.8

  selective cathepsin B inhibitors have previously been synthesized based upon the natural product cysteine protease inhibitor E-64. X-ray crystal data indicates that these compounds interact through their free carboxylate with the positively charged histidine residues located on the prime-side of the active site within the occluding loop of cathepsin B. Herein, we examine the pH dependence of two prime-side-binding

  以前已经基于天然产物半胱氨酸蛋白酶抑制剂E-64合成了强力和选择性组织蛋白酶B抑制剂。X射线晶体数据表明，这些化合物通过其游离羧酸盐与位于组织蛋白酶B闭塞环内活性位点主端的带正电荷的组氨酸残基相互作用。在此，我们研究了两个主端的pH依赖性结合化合物。在每种情况下，随着pH从4升高到7.8（对应于pK（a）4.4的单个电离），k（inact）/ K（I）都会显着降低。这些结果表明，如果酶环境的pH值大于5.5，靶向组织蛋白酶B的闭环可能是不良的抑制剂设计策略。然而，
• E-64 analogues as inhibitors of cathepsin B. On the role of the absolute configuration of the epoxysuccinyl group
  作者：Norbert Schaschke、Irmgard Assfalg-Machleidt、Werner Machleidt、Dushan Turk、Luis Moroder

  DOI：10.1016/s0968-0896(97)00105-3

  日期：1997.9

  A series of trans-epoxysuccinyl-peptide derivatives based on the natural inhibitor E-64 were synthesized in the (2R,3R) and (2S,3S) configuration in order to analyze the role of the stereochemistry of this residue in dictating inhibitory potency and selectivity for cysteine proteases. We confirmed that binding of E-64 like trans-epoxysuccinyl compounds is remarkably favored by the (2S,3S) con figuration, but we also found that CA030-type compounds are stronger inhibitors in the (2R,3R) configuration than the related diastereomers. Consequently, the structural requirements for exploiting both the S and S' subsites are not additive and a structure-based design of bis-peptidyl derivatives of trans-epoxysuccinic acid to increase selective inhibition becomes even more difficult. Additional contrasting effects were observed for the pH optima required in the electrostatic interactions at the S and S' subsites. (C) 1997 Elsevier Science Ltd.
• First Total Synthesis of Leucamide A
  作者：Wenlong Wang、Fajun Nan

  DOI：10.1021/jo026799+

  日期：2003.2.1

  The first total synthesis of marine bioactive cyclic heptapeptide Leucamide A has been accomplished, including a simple method for construction of the 4,2-bisheterocycle tandem pair substructure that employs a DAST-mediated cyclization of beta-hydroxy amide and final HBTU-promoted ring closing.