(2S,3R)-methyl-2-(4-methoxybenzamido)-3-hydroxybutanoate | 704910-28-1

• 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: (2S,3R)-methyl-2-(4-methoxybenzamido)-3-hydroxybutanoate
• 英文别名: (2S,3R)-3-hydroxy-2-(4-methoxybenzamido)-butyric acid methyl ester；Bz(4-OMe)-L-Thr-OMe；methyl (2S,3R)-3-hydroxy-2-(4-methoxybenzamido)butanoate；methyl (2S,3R)-3-hydroxy-2-[(4-methoxybenzoyl)amino]butanoate
• CAS: 704910-28-1
• 化学式: C₁₃H₁₇NO₅
• 分子量: 267.282
• InChiKey: IVGPUIRENVPOMY-KCJUWKMLSA-N

物化性质

• 熔点：
  108.0-109.0 °C(Solv: ethyl acetate (141-78-6); ethyl ether (60-29-7))
• 沸点：
  495.4±45.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-methyl-2-(4-methoxybenzamido)-3-hydroxybutanoate 在 六甲基磷酰三胺 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 29.0h， 生成 methyl (2R,3R)-2-(4-methoxybenzylamino)-2-{(benzyloxy)methyl}-3-hydroxybutanoate
  参考文献：
  名称：

  salinosporamide A的简单立体控制合成。

  摘要：

  已经开发了简单有效的立体合成唾液孢酰胺A的合成方法。该方法是唾液孢酰胺A的首次合成，能够提供大量化合物用于进一步的生物学研究。Salinosporamide A作为合成靶标特别受关注，因为它对许多肿瘤细胞系具有强大的体外细胞毒活性（IC（50）值为10 nM或更小）。

  DOI：

  10.1021/ja048613p
• 作为产物：
  描述：

  L-苏氨酸甲酯盐酸盐 、 对甲氧基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以84%的产率得到(2S,3R)-methyl-2-(4-methoxybenzamido)-3-hydroxybutanoate
  参考文献：
  名称：

  绝对立体化学的测定，全合成和粘胶粘菌肽的评估。

  摘要：

  melleumin A（1）和B（2），即从粘菌皮生胶体中分离出的新型肽化合物，通过合成其片段和改进的Mosher方法来确定其绝对立体化学。melleumin B（2）的全合成是通过立体选择性方法实现的，这为melleumin B（2）的所有绝对立体化学提供了进一步的证据。评估了2及其10R受体19的Wnt信号抑制活性。化合物19显示出对Wnt信号转录的中度抑制，这表明蜜勒白胺类似物可用作Wnt信号抑制剂。

  DOI：

  10.1016/j.bmcl.2007.11.005

文献信息

• Synthesis of Substituted Oxazoles from<i>N</i>-Acyl-β-hydroxyamino Acid Derivatives
  作者：Paula M. T. Ferreira、Luís S. Monteiro、Goreti Pereira

  DOI：10.1002/ejoc.200800602

  日期：2008.9

  β-diiododehydroalanine derivatives. Although the reason for the different reactivities of the N-acyldehydroamino acids is not completely clear to us, cyclic voltammetry studies showed that the less-reactive derivatives have higher reduction potentials. This suggests that the double bonds in dehydroaminobutyric acid derivatives are more susceptible to electrophilic attack by iodine.(© Wiley-VCH Verlag GmbH & Co. KGaA

  制备了几种 N-酰基-β-羟基氨基酸，并在 4-（二甲氨基）吡啶存在下用二碳酸二叔丁酯处理，然后用 N,N,N',N'-四甲基胍处理，得到相应的N-酰基脱氢氨基酸的产率很高。然后用 I2/K2CO3 和 1,8-二氮杂双环 [5.4.0] undec-7-ene 处理这些。N-酰基脱氢氨基丁酸的甲酯以良好至高产率得到相应的取代恶唑。N-酰基脱氢苯丙氨酸与β-碘脱氢苯丙氨酸一起以低至中等产率得到5-苯基恶唑衍生物。在相同条件下，N-酰基脱氢丙氨酸不能得到相应的恶唑。然而，当反应在没有 DBU 的情况下进行时，可以分离出 β,β-二碘脱氢丙氨酸衍生物。尽管我们并不完全清楚 N-酰基脱氢氨基酸不同反应性的原因，但循环伏安法研究表明，反应性较低的衍生物具有更高的还原电位。这表明脱氢氨基丁酸衍生物中的双键更容易受到碘的亲电攻击。 (© Wiley-VCH Verlag GmbH & Co. KGaA
• Asymmetric Syntheses and Wnt Signal Inhibitory Activity of Melleumin A and Four Analogues of Melleumins A and B
  作者：Jie-Min Luo、Chao-Feng Dai、Shu-Yong Lin、Pei-Qiang Huang

  DOI：10.1002/asia.200800355

  日期：2009.2.2

  Guided by nature: A flexible and epimerization‐free approach for the asymmetric syntheses of melleumin A and four analogues of melleumins A and B was developed, which allowed confirming the stereochemistry at C‐4 of melleumin A, and revealed that the unnatural 4‐epi‐melleumin B possesses a modest inhibitory activity on Wnt signaling.

  自然指导：开发了一种灵活，无差向异构化的melleumin A的不对称合成方法以及melleumins A和B的四种类似物，从而证实了melleumin A在C-4处的立体化学，并揭示了非天然的4- epi melleumin B对Wnt信号传导具有适度的抑制活性。
• Simple stereocontrolled synthesis of salinosporamide A
  申请人：Corey J. Elias

  公开号：US20050228186A1

  公开（公告）日：2005-10-13

  A simple and effective stereocontrolled synthesis of salinosporamide A (1) has been developed which follows the pathway outlined in the Figure. The process, the first total synthesis of salinosporamide A, is capable of providing the compound in substantial quantities for further biological studies. In addition to the method of Scheme I, the present invention also includes several novel synthetic intermediate compounds, several intermediate steps of the preferred synthetic process; and the uses of these compounds in the preparation of synthetic derivatives of the compound Salinosporamide A. Salinosporamide A is of special interest as a synthetic target because of its protein in vitro cytotoxic activity against many tumor cell lines (IC 50 values of 10 nM or less).

  已经开发出一种简单而有效的立体控制合成方法，用于制备Salinosporamide A (1)，该方法遵循图中概述的途径。这个过程是对Salinosporamide A的首次全合成，能够提供大量的化合物用于进一步的生物研究。除了方案I的方法之外，本发明还包括几种新颖的合成中间体化合物，首选合成过程的几个中间步骤；以及这些化合物在制备Salinosporamide A的合成衍生物中的用途。Salinosporamide A作为合成目标具有特殊的意义，因为它在体外对许多肿瘤细胞系的蛋白细胞毒活性(IC50值为10 nM或更低)。
• Determination of absolute stereochemistry, total synthesis, and evaluation of peptides from the myxomycete Physarum melleum
  作者：Shuwa Hanazawa、Midori A. Arai、Xiaofan Li、Masami Ishibashi

  DOI：10.1016/j.bmcl.2007.11.005

  日期：2008.1

  stereochemistry of melleumin A (1) and B (2), novel peptide compounds isolated from the myxomycete Physarum melleum, was determined by synthesis of their segments and by a modified Mosher's method. Total synthesis of melleumin B (2) was achieved by a stereoselective method, which provided further evidence for all the absolute stereochemistries of melleumin B (2). The Wnt signal inhibitory activities of 2 and

  melleumin A（1）和B（2），即从粘菌皮生胶体中分离出的新型肽化合物，通过合成其片段和改进的Mosher方法来确定其绝对立体化学。melleumin B（2）的全合成是通过立体选择性方法实现的，这为melleumin B（2）的所有绝对立体化学提供了进一步的证据。评估了2及其10R受体19的Wnt信号抑制活性。化合物19显示出对Wnt信号转录的中度抑制，这表明蜜勒白胺类似物可用作Wnt信号抑制剂。
• A mild high yielding synthesis of oxazole-4-carboxylate derivatives
  作者：Paula M.T. Ferreira、Elisabete M.S. Castanheira、Luís S. Monteiro、Goreti Pereira、Helena Vilaça

  DOI：10.1016/j.tet.2010.09.014

  日期：2010.11

  Several 2,5-disubstituted oxazole-4-carboxylates were prepared in high yields from the methyl esters of N-acyl-beta-halodehydroaminobutyric acid derivatives by treatment with a 2% solution of DBU in acetonitrile. The scope of this reaction was investigated and it was found that dehydrodipeptides having a beta-bromodehydroaminobutyric acid residue gave the corresponding oxazoles in good yields. The photophysical properties of some of the oxazoles prepared were studied in four solvents of different polarity. All compounds have reasonable high fluorescence quantum yields and a moderate solvent sensitivity, which makes them good candidates to be used as fluorescent probes. One of the fluorescent oxazoles prepared was inserted after cleavage of the methyl ester into two model peptides using a conventional solution phase strategy. The photophysical properties of the labelled peptides were studied in ethanol and water and compared with those of the oxazole. The results obtained showed that the oxazole maintains a good fluorescence level and the same solvent sensitivity when linked to a peptide chain. (C) 2010 Elsevier Ltd. All rights reserved.