(R)-2-溴琥珀酸 | 3972-41-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (R)-2-溴琥珀酸
• 英文名称: (R)-2-bromosuccinic acid
• 英文别名: (R)-bromosuccinic acid；(2R)-2-bromobutanedioic acid
• CAS: 3972-41-6
• 化学式: C₄H₅BrO₄
• 分子量: 196.985
• InChiKey: QQWGVQWAEANRTK-UWTATZPHSA-N

物化性质

• 熔点：
  166-167 °C
• 沸点：
  255.1±25.0 °C(Predicted)
• 密度：
  2.022±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于乙腈（轻微）、甲醇（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2-溴琥珀酸 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 以87%的产率得到(R)-2-bromobutane-1,4-diol
  参考文献：
  名称：

  Acyclic butyl nucleic acid (BuNA): a novel scaffold for A-switch

  摘要：

  构建了一种A开关，该开关源自一种名为无环丁基核酸（BuNA）的人工核酸。首先，合成了(S)-BuNA的磷酰胺化学构件，原料为(R)-天冬氨酸。为了展示其作为A开关的用途，研究了(S)-BuNA的聚腺苷酸核苷酸序列在中性和酸性条件下的圆二色性（CD）和紫外光（UV）光谱。酸碱滴定揭示了在pH 4.8处的两个状态转变以及高度pH依赖的结构构象可逆性。热融化（Tm）研究表明，在中性pH下，聚BuNA(A)是一个弱有序的单链，而在低pH下，它则采用高度有序和刚性结构。此外，MALDI-TOF-MS数据显示出分子间的相互作用，这导致形成了由双螺旋结构组成的A基元。由于BuNA在酸性条件下不会发生去嘌呤作用，这使我们能够确定A基元的热力学参数。这是首次报道使用人工核酸构建A开关。

  DOI：

  10.1039/c3ra41255e
• 作为产物：
  描述：

  DL-天门冬氨酸 在 硫酸 、 potassium bromide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 3.0h， 生成 (R)-2-溴琥珀酸
  参考文献：
  名称：

  Identification and pharmacological characterization of succinate receptor agonists

  摘要：

  Background and PurposeThe succinate receptor (formerly GPR91 or SUCNR1) is described as a metabolic sensor that may be involved in homeostasis. Notwithstanding its implication in important (patho)physiological processes, the function of succinate receptors has remained ill‐defined because no pharmacological tools were available. We report on the discovery of the first family of potent synthetic agonists.Experimental ApproachWe screened a library of succinate analogues and analysed their activity on succinate receptors. Also, we modelled a pharmacophore and a binding site for this receptor. New agonists were identified based on the information provided by these two approaches. Their activity was studied in various bioassays, including measurement of cAMP levels, [Ca2+]i mobilization, TGF‐α shedding and recruitment of arrestin 3. The in vivo effects of activating succinate receptors with these new agonists was evaluated on rat BP.Key ResultsWe identified cis‐epoxysuccinic acid and cis‐1,2‐cyclopropanedicarboxylic acid as agonists with an efficacy similar to that of succinic acid. Interestingly, cis‐epoxysuccinic acid was 10‐ to 20‐fold more potent than succinic acid on succinate receptors. For example, cis‐epoxysuccinic acid reduced cAMP levels with a pEC50 = 5.57 ± 0.02 (EC50 = 2.7 μM), compared with succinate pEC50 = 4.54 ± 0.08 (EC50 = 29 μM). The rank order of potency of the three agonists was the same in all in vitro assays. Both cis‐epoxysuccinic and cis‐1,2‐cyclopropanedicarboxylic acid were as potent as succinate in increasing rat BP.Conclusions and ImplicationsWe describe new agonists at succinate receptors that should facilitate further research on this understudied receptor.

  DOI：

  10.1111/bph.13738

文献信息

• Total Synthesis of the Bacterial RNA Polymerase Inhibitor Ripostatin B
  作者：Florian Glaus、Karl-Heinz Altmann

  DOI：10.1002/anie.201200871

  日期：2012.4.2

  A modular and highly stereoselective synthesis of the title compound was developed. Key steps in the assembly of the carbon framework of ripostatin B (1; see scheme) were a stereoselective Paterson aldol reaction and a high‐yielding ring‐closing metathesis mediated by Grubbs first generation catalyst. The C15 hydroxy group was established through Tishchenko–Evans reduction in excellent yield and selectivity

  开发了标题化合物的模块化和高度立体选择性的合成。组装ripostatin B碳骨架的关键步骤（见方案1）是立体选择性的Paterson aldol反应和由Grubbs第一代催化剂介导的高产闭环复分解反应。通过Tishchenko-Evans还原，以优异的收率和选择性建立了C15羟基。
• Design, synthesis, biophysical and primer extension studies of novel acyclic butyl nucleic acid (BuNA)
  作者：Vipin Kumar、Kiran R. Gore、P. I. Pradeepkumar、Venkitasamy Kesavan

  DOI：10.1039/c3ob41244j

  日期：——

  that (S)-BuNA is capable of making duplexes with its complementary strands and integration of (S)-BuNA nucleotides into DNA duplex does not alter the B-type-helical structure of the duplex. Furthermore, (S)-BuNA oligonucleotides and (S)-BuNA substituted DNA strands were studied as primer extensions by DNA polymerases. This study revealed that the acyclic scaffold is tolerated by enzymes and is therefore

  合成了一种新的核酸类似物，称为无环（S）-丁基核酸（BuNA），其由含有磷酸二酯键并带有天然核碱基的无环骨架组成。接下来，将（S）-BuNA核苷酸掺入DNA链中，研究其对双链体稳定性和结构构象变化的影响。圆二色性（CD），UV熔解和非变性凝胶电泳（天然PAGE）研究表明（S）-BuNA能够与其互补链形成双链体，而（S）-BuNA核苷酸整合到DNA双链体中却没有改变双链体的B型螺旋结构。此外，（S）-BuNA寡核苷酸和（S）-BuNA取代的DNA链被DNA聚合酶研究为引物延伸。这项研究表明，无环支架可以被酶所耐受，因此在某种程度上具有生物相容性。
• Total Synthesis of (−)-Zampanolide and Structure-Activity Relationship Studies on (−)-Dactylolide Derivatives
  作者：Didier Zurwerra、Florian Glaus、Leo Betschart、Julia Schuster、Jürg Gertsch、Walter Ganci、Karl-Heinz Altmann

  DOI：10.1002/chem.201202553

  日期：2012.12.21

  A new total synthesis of the marine macrolide (−)‐zampanolide (1) and the structurally and stereochemically related non‐natural levorotatory enantiomer of (+)‐dactylolide (2), that is, ent‐2, has been developed. The synthesis features a high‐yielding, selective intramolecular Horner–Wadsworth–Emmons (HWE) reaction to close the 20‐membered macrolactone ring of 1 and ent‐2. The β‐keto phosphonate/aldehyde

  已经开发了一种新的海洋大环内酯（-）-樟脑内酯（1）以及结构和立体化学相关的非天然左旋对映异构体（+）-内酯（2）（即eNT - 2）的新合成方法。合成有高产，选择性分子内霍纳-沃兹沃思-埃蒙斯（HWE）反应以关闭的20元大环内酯1和ENT - 2。β-酮膦酸酯/醛用于闭环反应的前体是通过将ω-二乙基膦酰基羧酸片段和带有THP环的仲醇片段酯化而获得的，THP环嵌入在1和eNT - 2的大环核结构中。THP环的形成是通过片段偶联Prins型环化完成的。采用相同的整体策略，13- desmethylene- ENT - 2以及4的单环desTHP衍生物1个ENT - 2制备。合成1通过n M IC 50抑制人癌细胞的体外生长值eNT - 2缺少含二烯的半胱氨酸连接侧链1，而其活性降低了25到260倍。13 Desmethylene- ENT - 2以及减小的版本ENT - 2和13-desmethylene-
• Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines
  作者：Benjamin L. Lu、Geoffrey M. Williams、Daniel J. Verdon、P. Rod Dunbar、Margaret A. Brimble

  DOI：10.1021/acs.jmedchem.9b01044

  日期：2020.3.12

  immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing “danger signals” in order

  与更传统的治疗方式相比，癌症免疫疗法由于其潜在的特异性和缺乏不良副作用而受到越来越多的关注。Toll样受体2（TLR2）激动剂是脂肽，具有S- [2,3-双（棕榈酰氧基）丙基] -1-半胱氨酸（Pam 2 Cys）基序，并表现出强大的免疫刺激作用。这些激动剂提供了一种提供“危险信号”的方式，以激活针对肿瘤抗原的免疫系统。因此，在寻找潜在的癌症免疫刺激剂方面，TLR2激动剂的开发具有吸引力。Pam 2的现有SAR研究带有TLR2的半胱氨酸表明，对活性的结构要求在大多数情况下是非常难以忍受的。我们已经研究了立体化学的重要性，N末端酰化的影响以及Pam 2 Cys结合的脂肽中两个酯官能团之间对TLR2活性的同源性。的[R非对映体是显著比更有效小号非对映体和Ñ末端修饰通常降低TLR2活性。最显着地，同源性产生了对含有天然Pam 2 Cys的构建体具有相对活性的类似物。
• Synthesis of (−)-Dactylolide and 13-Desmethylene-(−)-dactylolide and Their Effects on Tubulin
  作者：Didier Zurwerra、Jürg Gertsch、Karl-Heinz Altmann

  DOI：10.1021/ol100665m

  日期：2010.5.21

  An efficient new synthesis has been elaborated for non-natural (−)-dactylolide ((−)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (−)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the

  一种有效的新的合成已详细阐述了非天然的（ - ） - dactylolide（（ - ） - 2）和它的13-desmethylene类似物4，采用具有β酮基膦酸酯基于HWE-大环化方法/醛19和相应的13-去甲亚甲基衍生物为关键中间体。（-）- 2和4以及相应的C20醇均以亚微摩尔范围的IC 50值抑制人癌细胞的增殖，并在体外诱导微管蛋白的聚合。