(S)-2-isobutylsuccinic acid 4-O-t-butyl ester | 157542-03-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-2-isobutylsuccinic acid 4-O-t-butyl ester
• 英文别名: (S)-2-(2-(tert-butoxy)-2-oxoethyl)-4-methylpentanoic acid；2-(2-methylpropyl)-1,4-butanedioic acid 4-(1,1-dimethylethyl)ester；(2S)-4-methyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid
• CAS: 157542-03-5
• 化学式: C₁₂H₂₂O₄
• 分子量: 230.304
• InChiKey: NPIMKSLXCPUXPD-VIFPVBQESA-N

物化性质

• 沸点：
  324.7±25.0 °C(Predicted)
• 密度：
  1.021±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-isobutylsuccinic acid 4-O-t-butyl ester 在 镍 正丁基锂 、 sodium azide 、 dimethyl sulfide borane 、 氢溴酸 、 氢气 、 对甲苯磺酸 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二甲基亚砜 为溶剂， -78.0~60.0 ℃ 、330.95 kPa 条件下， 反应 46.33h， 生成 (4S)-isobutyl-(3S)-methylpyrrolidin-2-one
  参考文献：
  名称：

  Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein

  摘要：

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

  DOI：

  10.1021/jm049762l
• 作为产物：
  描述：

  4-甲基戊酸 在 lithium hydroxide monohydrate 、 双氧水 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 65.58h， 生成 (S)-2-isobutylsuccinic acid 4-O-t-butyl ester
  参考文献：
  名称：

  Design and synthesis of the stabilized analogs of belactosin A with the unnatural cis-cyclopropane structure

  摘要：

  具有非天然顺式环丙烷结构的贝拉可素A类似物2a，其作为蛋白酶体抑制剂的效力远超具有反式环丙烷结构的贝拉可素A。然而，其抑制细胞生长的效果却远低于从其显著的蛋白酶体抑制效果中所预期的水平，这可能归因于其在细胞环境下的不稳定性。我们假设2a的不稳定性源于其受压的β-内酯环的化学和酶促水解。因此，为了通过化学修饰增强2a的稳定性，我们设计并合成了具有空间位阻更大的β-内酯环和/或基于环丙烷张力的构象限制的类似物，从而鉴定出稳定化的类似物6a，它是一种具有细胞生长抑制效应的蛋白酶体抑制剂。我们的发现表明，2a的化学和生物稳定性显著受到其β-内酯羰基周围空间位阻和分子构象灵活性的影响。

  DOI：

  10.1039/c3ob41338a

文献信息

• Design and synthesis of the stabilized analogs of belactosin A with the unnatural cis-cyclopropane structure
  作者：Shuhei Kawamura、Yuka Unno、Akira Asai、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1039/c3ob41338a

  日期：——

  The belactosin A analog 2a, having the unnatural cis-cyclopropane structure instead of the trans-cyclopropane structure in belactosin A, is a much more potent proteasome inhibitor than belactosin A. However, its cell growth inhibitory effect is rather lower than that expected from its remarkable proteasome inhibitory effect, probably due to its instability under cellular conditions. We hypothesized that the instability of 2a was due to chemical and enzymatic hydrolysis of the strained β-lactone moiety. Thus, to increase the stability of 2a by chemical modification, its analogs with a sterically more hindered β-lactone moiety and/or cyclopropylic strain-based conformational restriction were designed and synthesized, resulting in the identification of a stabilized analog 6a as a proteasome inhibitor with cell growth inhibitory effects. Our findings suggest that the chemical and biological stability of 2a is significantly affected by the steric hindrance around its β-lactone carbonyl moiety and the conformational flexibility of the molecule.

  具有非天然顺式环丙烷结构的贝拉可素A类似物2a，其作为蛋白酶体抑制剂的效力远超具有反式环丙烷结构的贝拉可素A。然而，其抑制细胞生长的效果却远低于从其显著的蛋白酶体抑制效果中所预期的水平，这可能归因于其在细胞环境下的不稳定性。我们假设2a的不稳定性源于其受压的β-内酯环的化学和酶促水解。因此，为了通过化学修饰增强2a的稳定性，我们设计并合成了具有空间位阻更大的β-内酯环和/或基于环丙烷张力的构象限制的类似物，从而鉴定出稳定化的类似物6a，它是一种具有细胞生长抑制效应的蛋白酶体抑制剂。我们的发现表明，2a的化学和生物稳定性显著受到其β-内酯羰基周围空间位阻和分子构象灵活性的影响。
• N-Sulfonyl dipeptide nitriles as inhibitors of human cathepsin S: In silico design, synthesis and biochemical characterization
  作者：Carina Lemke、Lorenzo Cianni、Christian Feldmann、Erik Gilberg、Jiafei Yin、Fernanda dos Reis Rocho、Daniela de Vita、Ulrike Bartz、Jürgen Bajorath、Carlos A. Montanari、Michael Gütschow

  DOI：10.1016/j.bmcl.2020.127420

  日期：2020.9

  A library of cathepsin S inhibitors of the dipeptide nitrile chemotype, bearing a bioisosteric sulfonamide moiety, was synthesized. Kinetic investigations were performed at four human cysteine proteases, i.e. cathepsins S, B, K and L. Compound 12 with a terminal 3-biphenyl sulfonamide substituent was the most potent (Ki = 4.02 nM; selectivity ratio cathepsin S/K = 5.8; S/L = 67) and 24 with a 4’-fluoro-4-biphenyl

  合成了具有生物等排性磺酰胺部分的二肽腈化学型的组织蛋白酶S抑制剂库。在四种人半胱氨酸蛋白酶，即组织蛋白酶S，B，K和L上进行了动力学研究。具有末端3-联苯磺酰胺取代基的化合物12最有效（K i = 4.02 nM；组织蛋白酶S / K的选择性比= 5.8； S / L = 67）和24用4'-氟-4-联苯基磺酰胺取代基的最有选择性的组织蛋白酶S抑制剂（ķ我= 35.5纳米;选择性比率组织蛋白酶S / K = 57; S / L = 31）。电脑 设计和生化评估强调了磺酰胺键对选择性的影响以及就组织蛋白酶S的相应结合位点而言P2和P3取代基的可能转换。
• SAR Studies of the Leupyrrins: Design and Total Synthesis of Highly Potent Simplified Leupylogs
  作者：Paul R. Wosniok、Christopher Knopf、Sandra Dreisigacker、J. Manuel Orozco‐Rodriguez、Bettina Hinkelmann、Peter P. Mueller、Mark Brönstrup、Dirk Menche

  DOI：10.1002/chem.202002622

  日期：2020.11.26

  agents. A structure–activity‐relationship study of natural and synthetic derivatives is reported which reveals important insights into the biological relevance of several structural subunits leading to the discovery of highly potent but drastically simplified leupylogs that incorporate a stable and readily available aromatic side chain. For their synthesis a concise strategy is described that enables

  亮丙瑞林是高度有效的抗真菌剂。报道了对天然和合成衍生物的结构-活性-关系研究，该研究揭示了对几种结构亚基的生物学相关性的重要见解，从而导致发现了具有稳定且易于获得的芳族侧链的高效但显着简化的亮链木。对于它们的综合，描述了一种简明的策略，该策略允许进行短而通用的访问。
• SYNTHESIS OF ARYL CYCLOHEXANE CARBOXAMIDE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS
  申请人：The Procter & Gamble Company

  公开号：US20170057911A1

  公开（公告）日：2017-03-02

  Synthesis methods to produce a series of carboxamides built off of an (S)-2-amino acid backbone or an (R)-2-amino acid backbone, depending upon the desired diastereomer of the end product.

  合成方法可用于在(S)-2-氨基酸骨架或(R)-2-氨基酸骨架上构建一系列羧酰胺，具体取决于所需的最终产物的对映异构体。
• Total Synthesis of Leupyrrins A₁and B₁, Highly Potent Antifungal Agents from the Myxobacterium<i>Sorangium cellulosum</i>
  作者：Sebastian Thiede、Paul R. Wosniok、Daniel Herkommer、Thomas Debnar、Maoqun Tian、Tongtong Wang、Michael Schrempp、Dirk Menche

  DOI：10.1002/chem.201604445

  日期：2017.3.8

  involving a one‐pot lactol opening, stereoselective aldehyde addition and in situ lactonization. Furthermore, an innovative sp2‐sp3‐cross‐coupling for pyrrole functionalization and an optimized HATU‐mediated amide coupling protocol of two elaborate fragments were established. In addition, an unusual protective group strategy, involving a Teoc‐acetonide protected amine in combination with tert‐butyl

  报告了有关高产量的全合成亮丙氨酸酯酶A 1和B 1的有效策略的设计，详细说明和应用的详细信息，这是得自粘胶纤维梭菌的独特抗真菌剂。连续的锆茂介导的二炔环化和氧化锆环戊二烯中间体的区域选择性开放使简洁地进入独特的二氢呋喃片段成为可能，而丁内酯的另一种多米诺反应涉及单锅内酯开口，立体选择性醛加成和原位内酯化。此外，创新的sp 2 ‐sp 3建立了吡咯功能化的交叉偶联和两个精细片段的优化的HATU介导的酰胺偶联方案。此外，成功地制定了一种不寻常的保护基策略，其中包括由Teoc-丙酮化物保护的胺与叔丁基酯和乙酸酯的组合。这些策略和策略通常是有用的，也可用于其他功能化化合物的合成。预期通过这些总合成获得的材料将能够进一步探索这些有效的抗真菌剂的生物学特性。