{2-[benzyl-(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester | 1353048-74-4

• 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-[benzyl-(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester
• 英文别名: {2-[benzyl(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester；Benzyl 2-[[2-[benzyl(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoyl]amino]acetate
• CAS: 1353048-74-4
• 化学式: C₃₂H₄₂N₂O₆
• 分子量: 550.695
• InChiKey: UQRPICCUKRUPMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  {2-[benzyl-(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester 在 4-二甲氨基吡啶 、 sodium hydride 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 (2-{benzyl[2-(toluene-4-sulfonyloxymethyl)acryloyl]amino}-4-methylpentanoylamino)acetic acid benzyl ester
  参考文献：
  名称：

  Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System

  摘要：

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.

  DOI：

  10.1021/jm201359d
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 在 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 {2-[benzyl-(1,5-dioxaspiro[5.5]undecane-3-carbonyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester
  参考文献：
  名称：

  Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System

  摘要：

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.

  DOI：

  10.1021/jm201359d

文献信息

• Studies towards enzymatic kinetic resolutions of 1,3-diol peptidomimetics obtained via the Ugi reaction
  作者：Szymon Kłossowski、Adam Redzej、Sara Szymkuć、Ryszard Ostaszewski

  DOI：10.3998/ark.5550190.p008.122

  日期：——

  Enzymatic methods in combination with the multicomponent Ugi condensation make a very efficient method for simple synthesis of non-racemic peptidomimetics. The aim of the studies was to develop an enzymatic kinetic resolution of 1,3-diol peptidomimetics providing nonracemic compounds. Among many applications, 1,3-diols can serve as intermediates in the synthesis of anticancer agents β-acyloxymethacrylic

  酶促方法与多组分 Ugi 缩合相结合，是一种非常有效的非外消旋肽模拟物的简单合成方法。研究的目的是开发 1,3-二醇肽模拟物的酶动力学拆分，提供非外消旋化合物。在许多应用中，1,3-二醇可作为合成抗癌剂β-酰氧基甲基丙烯酰胺的中间体。研究了 Ugi 产品的立体选择性酶促酰化和水解。在两种情况下都确定了对映体或非对映体过量。因此，开发了一种用于合成手性、非外消旋 1,3-二醇肽模拟物的有效酶促方法。
• Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System
  作者：Szymon Kłossowski、Angelika Muchowicz、Małgorzata Firczuk、Marta Świech、Adam Redzej、Jakub Golab、Ryszard Ostaszewski

  DOI：10.1021/jm201359d

  日期：2012.1.12

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.