DL-aspartic acid dimethyl ester hydrochloride | 32213-95-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 天冬氨酸类衍生物
• 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: DL-aspartic acid dimethyl ester hydrochloride
• 英文别名: dimethyl aspartate hydrochloride；aspartic acid dimethyl ester hydrochloride；(1,4-Dimethoxy-1,4-dioxobutan-2-yl)azanium;chloride
• CAS: 32213-95-9
• 化学式: C₆H₁₁NO₄*ClH
• 分子量: 197.619
• InChiKey: PNLXWGDXZOYUKB-UHFFFAOYSA-N

物化性质

• 熔点：
  115-117 °C(lit.)
• 比旋光度：
  15 º (c=1, MeOH)
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.53
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  78.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  2922499990
• 危险品运输编号：
  NONH for all modes of transport
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

应用

L-天冬氨酸的二甲酯盐酸盐是白色晶体，在生物合成化学、药物化学、食品加工和光学活性材料等领域中作为重要原料。

制备

在磁力搅拌下，将氯化亚砜缓慢滴加到无水甲醇中，并控制温度在－10～－5 ℃之间。滴加完毕后，保持－10 ℃持续搅拌并反应一段时间(t A)，以生成氯化亚硫酸甲酯。随后，分批加入相应的L-天冬氨酸，在恒定温度T A下继续搅拌反应一段时间(t B)。

接着进行减压蒸馏，加入甲醇，再重复几次减压蒸馏步骤，尽量除去未反应的氯化亚砜以及生成的氯化氢，使产物以固体形式析出。使用溶剂重结晶时，需注意甲醇的比例：比例过高，则产物较难析出且产率较低；比例过低，则产物不易溶解，需要更多的溶剂量。当甲醇和乙酸乙酯的体积比为1∶20时，重结晶效率最高，产率为95%。

反应信息

• 作为反应物：
  描述：

  DL-aspartic acid dimethyl ester hydrochloride 在 溶剂黄146 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 20.0h， 生成 Dimethyl 2-[2-(2,2,2-trichloroacetyl)pyrrol-1-yl]butanedioate
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  (R)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners

  摘要：

  A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo- [1,2-a][1,2a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)enantiomer 44 (SX-3202): From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.

  DOI：

  10.1021/jm9802968
• 作为产物：
  描述：

  甲醇 、 DL-天门冬氨酸 在 三甲基氯硅烷 作用下， 反应 12.0h， 以86%的产率得到DL-aspartic acid dimethyl ester hydrochloride
  参考文献：
  名称：

  一种方便合成的氨基酸甲酯。

  摘要：

  在三甲基氯硅烷存在下，通过氨基酸与甲醇的室温反应，制备了一系列氨基酸甲酯盐酸盐，收率良好至极好。该方法不仅与天然氨基酸相容，而且与其他芳香族和脂肪族氨基酸相容。

  DOI：

  10.3390/molecules13051111

文献信息

• SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20150152108A1

  公开（公告）日：2015-06-04

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥式脲化合物，相应的相关类似物，药物组合物以及其使用方法。本发明的抑制素调节化合物可用于延长细胞寿命，并治疗和/或预防各种疾病和疾病，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块疾病、炎症、癌症和/或潮红有关的疾病或疾病，以及那些会受益于增加线粒体活性的疾病或疾病。本发明还涉及包含抑制素调节化合物与另一治疗剂组合的组合物。
• [EN] SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS<br/>[FR] ANALOGUES D'URÉE PONTÉS SUBSTITUÉS EN TANT QUE MODULATEURS DE SIRTUINE
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2016079709A1

  公开（公告）日：2016-05-26

  The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.

  本发明涉及一种新型的取代桥式脲类似物化合物，其化学式为（I）或其药学上可接受的盐，相应的药物组合物，制备这种化合物的方法以及单独使用或与其他治疗剂联合使用的这些化合物作为Sirtuin调节剂，可用于增加细胞寿命，并用于治疗和/或预防各种疾病和紊乱，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块紊乱、炎症、癌症和/或潮红有关的疾病或紊乱，以及那些会受益于增加线粒体活性的疾病或紊乱。
• COMPOSITIONS AND METHODS FOR DETECTING NERVE AGENTS
  申请人：Corcoran Robert C.

  公开号：US20100130757A1

  公开（公告）日：2010-05-27

  The present invention provides methods and compositions for detecting, identifying and measuring the abundance of chemical nerve agents. Methods and compositions of the present invention are capable of providing selective detection of phosphorous based nerve agents, such as nerve agents that are esters of methyl phosphonic acid derivatives incorporating a moderately good leaving group at the phosphorus. Selectivity in the present invention is provided by a sensor composition having an alpha (α) effect nucleophile group that undergoes specific nucleophilic substitution and rearrangement reactions with phosphorus based nerve agents having a tetrahederal phosphorous bound to oxygen. The present invention includes embodiments employing a sensor composition further comprising a reporter group covalently linked to the alpha effect nucleophile group allowing rapid optical readout of nerve agent detection events, including direct visual readout and optical readout via spectroscopic analysis.

  本发明提供了用于检测、识别和测量化学神经毒剂丰度的方法和组合物。本发明的方法和组合物能够选择性地检测基于磷的神经毒剂，例如酯化了在磷上具有中等良好离去基团的甲基膦酸衍生物的神经毒剂。本发明中的选择性是通过具有α效应亲核基团的传感器组合物提供的，该亲核基团与磷基神经毒剂发生特定的亲核取代和重排反应，其中磷与氧结合形成四面体磷。本发明包括采用传感器组合物的实施例，该传感器组合物进一步包括与α效应亲核基团共价连接的报告基团，允许对神经毒剂检测事件进行快速光学读数，包括直接视觉读数和通过光谱分析的光学读数。
• Microwave-Assisted Ruthenium-Catalysed <i>ortho</i> -C−H Functionalization of <i>N</i> -Benzoyl <i>α</i> -Amino Ester Derivatives
  作者：Nandini Sharma、Vijay Bahadur、Upendra K. Sharma、Debasmita Saha、Zhenghua Li、Yogesh Kumar、Jona Colaers、Brajendra K Singh、Erik V. Van der Eycken

  DOI：10.1002/adsc.201800458

  日期：2018.8.17

  A microwave‐assisted highly efficient intermolecular C−H functionalization sequence has been developed to access substituted isoquinolones using α‐amino acid esters as a directing group. This methodology enables a wide range of N‐benzoyl α‐amino ester derivatives to react via a Ru‐catalysed C−H bond activation sequence, to form isoquinolones with moderate to excellent yields. As an additional advantage

  微波辅助高效分子间C-H官能化序列已经发展到使用访问取代的异喹诺酮化合物α -氨基乙酸酯定向基团。这种方法可以使大量的N-苯甲酰基α-氨基酯衍生物通过Ru催化的CH键激活序列反应，以中等到极好的收率形成异喹诺酮类化合物。作为一个额外的优势，我们的策略被证明具有广泛的适用性，并且还使烯烃的反应能够提供链烯基化的苯甲酰胺的途径。该方法还扩展到异喹啉生物碱衍生物的合成，即。氧鸟嘌呤和二肽。所开发的方案既简单又便宜，避免了繁琐的后处理程序，并在MW辐射下有效地工作。
• Reactivity and mechanism of α-nucleophile scaffolds as catalytic organophosphate scavengers
  作者：Pamela T. Wong、Somnath Bhattacharjee、Jayme Cannon、Shengzhuang Tang、Kelly Yang、Sierra Bowden、Victoria Varnau、Jessica J. O'Konek、Seok Ki Choi

  DOI：10.1039/c9ob00503j

  日期：——

  Design and in vitro validation of polar α-nucleophile scaffolds that offer potent catalytic reactivity and practical utility for organophosphate decontamination.

  设计和体外验证极性α-亲核试剂支架，提供强大的催化活性和实际用于有机磷去污的效用。

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