methyl (2R,3R)-2-(4-methoxybenzylamino)-2-{(benzyloxy)methyl}-3-hydroxybutanoate | 704910-31-6

• 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: methyl (2R,3R)-2-(4-methoxybenzylamino)-2-{(benzyloxy)methyl}-3-hydroxybutanoate
• 英文别名: methyl 2-(benzyloxymethyl)-3-hydroxy-2-(4-methoxybenzylamino)butanoate；(2R,3R)-methyl 2-(4-methoxybenzylamino)-2-((benzyloxy)methyl)-3-hydroxybutanoate；methyl (2R,3R)-3-hydroxy-2-[(4-methoxyphenyl)methylamino]-2-(phenylmethoxymethyl)butanoate
• CAS: 704910-31-6
• 化学式: C₂₁H₂₇NO₅
• 分子量: 373.449
• InChiKey: YNKYNRMRPRBVGZ-IIBYNOLFSA-N

物化性质

• 沸点：
  523.9±50.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2R,3R)-2-(4-methoxybenzylamino)-2-{(benzyloxy)methyl}-3-hydroxybutanoate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以72%的产率得到(R)-methyl 2-benzyloxymethyl-2-(4-methoxybenzylamino)-3-oxobutanoate
  参考文献：
  名称：

  Formal synthesis of salinosporamide A using a nickel-catalyzed reductive aldol cyclization–lactonization as a key step

  摘要：

  Application of a sequential nickel-catalyzed reductive aldol cyclization-lactonization reaction in a short formal synthesis of salinsporamide A, a potent 20S proteasome inhibitor and anti-cancer compound, is described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.06.038
• 作为产物：
  描述：

  methyl (4S,5R)-4-{[(benzyloxy)methyl]}-4,5-dihydro-2-(4-methoxyphenyl)-5-methyloxazole-4-carboxylate 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 反应 12.0h， 以90%的产率得到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

文献信息

• New synthetic route to access (±) salinosporamide A via an oxazolone-mediated ene-type reaction
  作者：Robert A. Mosey、Jetze J. Tepe

  DOI：10.1016/j.tetlet.2008.10.154

  日期：2009.1

  We report herein a racemic key intermediate in the synthesis of salinosporamide A via a tert-alkyl amino hydroxy carboxylic ester produced in an ene-type reaction of an oxazolone with an enol ether.

  我们在本文中报道了在恶唑酮与烯醇醚的烯型反应中通过叔烷基氨基羟基羧酸酯合成盐基孢酰胺A的外消旋关键中间体。
• 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)。
• Synthetic studies of salinosporamide A through the intramolecular hydroamidation of alkynes
  作者：Haruhi Kamisaki、Yusuke Kobayashi、Tetsutaro Kimachi、Yoshizumi Yasui、Yoshiji Takemoto

  DOI：10.1016/j.jorganchem.2010.06.021

  日期：2011.1

  Rhodium-catalyzed intramolecular hydroamidation of alkynes was carried out to construct the synthetic intermediates of a proteasome inhibitor, salinosporamide A. Several alkynyl formamides were synthesized and subjected to the hydroamidation reaction. Some derivatives with a methoxymethyl (MOM) or 2-methoxy-2-propyl (MOP) group near the reaction site were converted to the corresponding lactams in excellent yields. (C) 2010 Elsevier B.V. All rights reserved.
• [EN] ANALOGS OF SALINOSPORAMIDE A<br/>[FR] ANALOGUES DE SALINOSPORAMIDE A
  申请人：HARVARD COLLEGE

  公开号：WO2005099687A3

  公开（公告）日：2005-12-29
• US7183417B2
  申请人：——

  公开号：US7183417B2

  公开（公告）日：2007-02-27