(2R)-2-羟基戊二酸二甲酯 | 55094-98-9

• 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: (2R)-2-羟基戊二酸二甲酯
• 英文名称: dimethyl (R)-2-hydroxypentanedioate
• 英文别名: (+)-(R)-dimethyl 2-hydroxyglutarate；Dimethyl (2R)-2-hydroxypentanedioate
• CAS: 55094-98-9
• 化学式: C₇H₁₂O₅
• 分子量: 176.169
• InChiKey: SHBLBMNYOOCEFM-RXMQYKEDSA-N

物化性质

• 沸点：
  258.8±25.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-2-羟基戊二酸二甲酯 在 dimethyl sulfide borane 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 2.3h， 以99%的产率得到(R)-4,5-dihydroxypentanoic acid methyl ester
  参考文献：
  名称：

  首次全合成 4(R),17(R)-Resolvin D6 立体异构体，一种有效的神经保护二十二烷酸

  摘要：

  描述了一种新型神经保护 Resolvin D6 对映体 4( R ),17( R )-Resolvin D6 的首次全合成。Resolvin D6 是一种源自二十二碳六烯酸 (DHA, C22:6,  ω -3) 的脂质介质，具有抗炎特性。关键合成特征包括使用 MacMillan 对映选择性有机催化α -醛的氧化结合基于手性池的方法生成手性合成子、1,4-烯炔单元作为关键，以及 ( Z )-选择性Wittig 耦合组装 Resolvin D6 核心碳骨架。

  DOI：

  10.1016/j.tetlet.2022.154091
• 作为产物：
  描述：

  alpha-酮戊二酸 在 baker's yeast 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 生成 (2R)-2-羟基戊二酸二甲酯
  参考文献：
  名称：

  Enantiomerically pure tetrahydro-5-oxo-2-furancarboxylic esters from dialkyl 2-oxoglutarates

  摘要：

  Enantiomerically pure tetrahydro-5-oxo-2-furancarboxylic esters can be prepared either by enzymatic resolution of the racemic gamma-lactones themselves or by bioreduction with baker's yeast of dialkyl 2-oxoglutarates and subsequent cyclization of the resulting dialkyl 2-hydroxyglutarates. The best results were obtained by the former route, by which the desired compounds were isolated in high enantiomeric excess. Bioreductions were less satisfactory. In fact the hydroxyester intermediates were initially formed as racemic mixtures and their final enantiomeric enrichment was reached by asymmetric destruction, occurring in the bioreaction medium, however at the same time large amounts of alkyl 4-hydroxybutanoates were formed as side products. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00286-4

文献信息

• Transfer hydrogenation of activated ketones using novel chiral Ru(II)-N-arenesulfonyl-1,2-diphenylethylenediamine complexes
  作者：Damjan Šterk、Massoud S. Stephan、Barbara Mohar

  DOI：10.1016/j.tetlet.2003.10.201

  日期：2004.1

  A series of α-keto esters and α,α,α-trifluoromethyl ketones were reduced in high yields and excellent enantioselectivities under Ru-catalysed transfer hydrogenation using novel chiral N-arenesulfonyl-1,2-diphenylethylenediamine ligands.

  使用新型手性N-芳烃磺酰基-1,2-二苯基乙二胺配体，在Ru催化的转移氢化作用下，一系列α-酮酯和α，α，α-三氟甲基酮被还原，收率高，对映选择性优异。
• Discovery of LYC-55716: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ) Agonist for Use in Treating Cancer
  作者：Thomas D. Aicher、Chad A. Van Huis、Alexander R. Hurd、Donald J. Skalitzky、Clarke B. Taylor、Omar M. Beleh、Gary Glick、Peter L. Toogood、Bing Yang、Tao Zheng、Changxin Huo、Jie Gao、Chenxi Qiao、Xiaolong Tian、Junping Zhang、Kellie Demock、Ling-Yang Hao、Charles A. Lesch、Rodney W. Morgan、Jacques Moisan、Yahong Wang、JoAnn Scatina、Chrystal M. Paulos、Weiping Zou、Laura L. Carter、Xiao Hu

  DOI：10.1021/acs.jmedchem.1c00731

  日期：2021.9.23

  hypothesized to render immune infiltrates more effective at countering tumor growth. To test this hypothesis, a family of benzoxazines was optimized to provide LYC-55716 (37c), a potent, selective, and orally bioavailable small-molecule RORγ agonist. LYC-55716 decreases tumor growth and enhances survival in preclinical tumor models and was nominated as a clinical development candidate for evaluation in

  视黄酸受体相关孤儿受体 γ（RORc、RORγ 或 NR1F3）是核受体主转录因子，可驱动产生 IL-17 的 T 辅助细胞 (Th17)、细胞毒性 T 细胞 (Tc17) 和细胞的功能和发育。先天淋巴细胞的亚群。假设肿瘤微环境中 RORγ + T 细胞的激活可以使免疫浸润更有效地对抗肿瘤生长。为了检验这一假设，对苯并嗪家族进行了优化，以提供 LYC-55716 ( 37c )，这是一种有效的、选择性的、口服生物可利用的小分子 RORγ 激动剂。 LYC-55716 可减少临床前肿瘤模型中的肿瘤生长并提高生存率，并被提名为用于实体瘤患者评估的临床开发候选药物。
• [EN] Cyclic Ureas<br/>[FR] URÉES CYCLIQUES
  申请人：SU YANING

  公开号：WO2020103884A1

  公开（公告）日：2020-05-28

  Amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

  抑制细胞坏死和/或人类受体相互作用蛋白1激酶（RIP1）的酰胺，包括相应的磺胺酰胺和药用盐、水合物和立体异构体。这些化合物用于制备药物组合物，以及制备和使用方法，包括以有效量的化合物或组合物治疗需要的人，并检测人的健康或状况的改善。
• [EN] ARYL DIHYDRO-2H-BENZO[B][1,4]OXAZINE SULFONAMIDE AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORY AND THE TREATMENT OF DISEASE<br/>[FR] ARYL DIHYDRO-2H-BENZO[B][1,4]OXAZINE SULFONAMIDE ET COMPOSÉS APPARENTÉS DESTINÉS À ÊTRE UTILISÉS COMME AGONISTES DE RORΓ ET POUR LE TRAITEMENT DE MALADIES
  申请人：LYCERA CORP

  公开号：WO2016201225A1

  公开（公告）日：2016-12-15

  The invention provides aryl dihydro-2H-benzo[b] [l,4]oxazine sulfonamide and related compounds, pharmaceutical compositions, methods of promoting RORy activity, methods of increasing the amount of IL-17 in a subject, and methods of treating cancer and other medical disorders using such compounds.

  这项发明提供了芳基二氢-2H-苯并[b][1,4]噁嗪磺胺和相关化合物、药物组合物、促进RORγ活性的方法、增加受试者体内IL-17含量的方法，以及利用这些化合物治疗癌症和其他医学疾病的方法。
• [EN] METHODS OF TREATING DISEASE BY METABOLIC CONTROL OF T-CELL DIFFERENTIATION<br/>[FR] MÉTHODES DE TRAITEMENT DE MALADIES PAR LA RÉGULATION MÉTABOLIQUE DE LA DIFFÉRENCIATION DES LYMPHOCYTES T
  申请人：THE J DAVID GLADSTONE INST

  公开号：WO2017123808A1

  公开（公告）日：2017-07-20

  Provided herein are methods for treating an individual for a disease (e.g., an autoimmune disease or a cancer) using an active agent which affects metabolism of α-ketoglutarate (α-KG) and/or 2-hydroxyglutarate (2-HG) in differentiating T cells. In some embodiments, a Got1 inhibitor is used to generate a population of T cells enriched in peripheral regulatory T (iTreg) cells, which population enriched in iTreg cells may find use in treating an autoimmune disease. In some embodiments, a TCA cycle-associated metabolite, or a derivative thereof, is used to generate a population of T cells in enriched in IL-17- and IL-17F-producing CD4 T (TH17) cells, which population enriched in TH17 cells may find use in treating a cancer.

  本文提供了一种治疗个体患病（例如自身免疫疾病或癌症）的方法，使用影响α-酮戊二酸（α-KG）和/或2-羟基戊二酸（2-HG）在分化T细胞中代谢的活性剂。在某些实施例中，使用Got1抑制剂生成富集于外周调节性T细胞（iTreg）细胞的T细胞群，这种富集于iTreg细胞的群体可用于治疗自身免疫疾病。在某些实施例中，使用TCA循环相关代谢物或其衍生物生成富含IL-17和IL-17F产生的CD4 T（TH17）细胞的T细胞群，这种富含TH17细胞的群体可用于治疗癌症。