2-methylpropoxycarbonyl (2R)-2-(phenylmethoxycarbonylamino)propanoate | 102988-93-2

• 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: 2-methylpropoxycarbonyl (2R)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 102988-93-2
• 化学式: C₁₆H₂₁NO₆
• 分子量: 323.346
• InChiKey: ZYJYUYWMNOEKOI-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methylpropoxycarbonyl (2R)-2-(phenylmethoxycarbonylamino)propanoate 在 lithium aluminium tetrahydride 、 [VCl3(thf)3] 、 铜 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 dibenzyl ((2R,3S,4S,5R)-3,4-dihydroxyhexane-2,5-diyl)dicarbamate
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n
• 作为产物：
  描述：

  N-benzyloxycarbonyl-D-alanine 、 氯甲酸异丁酯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 2-methylpropoxycarbonyl (2R)-2-(phenylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Amino Acids and Peptides. XVI. Synthesis of N-Terminal Tetrapeptide Analogy of Fibrin .ALPHA.-Chain and Their Inhibitory Effects on Fibrinogen/Thrombin Clotting.

  摘要：

  采用溶液法和固相法合成了纤维蛋白α链的N端四肽类似物，使用了一种新的活性酯，即对硝基乙酰苯酮的腙酯。考察了它们对纤维蛋白原/凝血酶凝固的抑制作用。在合成的肽中，甘氨酸-脯氨酸-精氨酸-脯氨酸的酰胺类似物表现出更强的抑制效果。

  DOI：

  10.1248/cpb.40.3253

文献信息

• Amino Acids and Peptides. XVI. Synthesis of N-Terminal Tetrapeptide Analogy of Fibrin .ALPHA.-Chain and Their Inhibitory Effects on Fibrinogen/Thrombin Clotting.
  作者：Koichi KAWASAKI、Katsuhiko HIRASE、Masanori MIYANO、Toshiki TSUJI、Masanori IWAMOTO

  DOI：10.1248/cpb.40.3253

  日期：——

  N-Terminal tetrapeptide analogs of fibrin α-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.

  采用溶液法和固相法合成了纤维蛋白α链的N端四肽类似物，使用了一种新的活性酯，即对硝基乙酰苯酮的腙酯。考察了它们对纤维蛋白原/凝血酶凝固的抑制作用。在合成的肽中，甘氨酸-脯氨酸-精氨酸-脯氨酸的酰胺类似物表现出更强的抑制效果。
• Lenman, Morag M.; Lewis, Arwel; Gani, David, Journal of the Chemical Society. Perkin transactions I, 1997, # 16, p. 2297 - 2311
  作者：Lenman, Morag M.、Lewis, Arwel、Gani, David

  DOI：——

  日期：——
• Frakefamide, an Analgesic Tetrapeptide:  Development of a Pilot-Plant-Scale Process
  作者：Henry M. Franzén、Galina Bessidskaia、Vahak Abedi、Anders Nilsson、Maths Nilsson、Lars Olsson

  DOI：10.1021/op020060k

  日期：2002.11.1

  A pilot-plant-process is described where frakefamide x HCl (L-tyrosyl-D-alanyl-p-fluoro-L-phenylalanyl-L-phenylalaninamide hydrochloride) was synthesised from its amino acid monomers in seven steps. The synthesis was performed in 70-L equipment, and the final product was obtained in 70% overall yield and in 99.5% purity. Only two intermediates were isolated, and the process required no chromatography. Peptide bond formation was promoted by isobutyl chloroformate-mediated mixed anhydride coupling reactions. The formed mixed anhydrides proved to be surprisingly stable, in most cases for several hours at -10 degreesC, and therefore suitable for large-scale peptide synthesis. Only traces, if any, of racemised coupling products were obtained. Benzyloxycarbonyl was used as amino protecting group throughout the synthesis, and its removal by hydrogenolysis proved to be fast and convenient on a large scale.
• Design and Synthesis of Cyclopenta[<i>g</i>]quinazoline-Based Antifolates as Inhibitors of Thymidylate Synthase and Potential Antitumor Agents^,
  作者：Vassilios Bavetsias、Jonathan H. Marriott、Camille Melin、Rosemary Kimbell、Zbigniew S. Matusiak、F. Thomas Boyle、Ann L. Jackman

  DOI：10.1021/jm991119p

  日期：2000.5.1

  Following the development of raltitrexed, the synthesis of nonpolyglutamatable inhibitors of TS that do not use the reduced folate carrier (RFC) for cellular entry should provide compounds which overcome mechanisms of resistance to folate-based inhibitors of TS that are associated with decreased/altered folylpolyglutamate synthetase (FPGS) expression and/or an impaired RFC. Examination of a computer graphics model of the humanized Escherichia coli TS enzyme with quinazoline inhibitors of TS, such as 1 bound in the active site of the enzyme, suggested that conformational restriction introduced by bridging the C9 with C7 to form a pentacycle may be beneficial for binding to TS. That led to the synthesis of a series of potent cyclopenta[g]quinazoline-based inhibitors of the enzyme in which the glutamyl residue associated with classical antifolates was replaced with a variety of glutamate-derived ligands; the most potent inhibitor being the L-Glu-gamma-D-GluT(alpha) derivative 7j. In the mouse L1210:1565 cell line (mutant RFC), the majority of these compounds had activity equal or only slightly greater compared with the parental L1210 cell line, indicating a reduced dependence on the RFC for cellular uptake in the L1210 cell line.
• Pitzele; Hamilton; Kudla, Journal of Medicinal Chemistry, 1994, vol. 37, # 7, p. 888 - 896
  作者：Pitzele、Hamilton、Kudla、Tsymbalov、Stapelfeld、Savage、Clare、Hammond、Hansen Jr.

  DOI：——

  日期：——