1,2-di-tert-butyl (2S,4R)-4-(methanesulfonyloxy)pyrrolidine-1,2-dicarboxylate | 194163-72-9

• 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: 1,2-di-tert-butyl (2S,4R)-4-(methanesulfonyloxy)pyrrolidine-1,2-dicarboxylate
• 英文别名: (4R)-1-(tert-Butyloxycarbonyl)-4-(methanesulfonyloxy)-L-Proline tert-Butyl Ester；ditert-butyl (2S,4R)-4-methylsulfonyloxypyrrolidine-1,2-dicarboxylate
• CAS: 194163-72-9
• 化学式: C₁₅H₂₇NO₇S
• 分子量: 365.448
• InChiKey: UJUFLPYBFLRQRZ-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,2-di-tert-butyl (2S,4R)-4-(methanesulfonyloxy)pyrrolidine-1,2-dicarboxylate 在 sodium periodate 、 sodium azide 、 rhodium(III) chloride hydrate 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (2S,4R)-4-azido-N-tert-butoxycarbonylpyroglutamate
  参考文献：
  名称：

  A Highly Stereoselective and Scalable Synthesis of l-allo-Enduracididine

  摘要：

  A highly stereoselective and scalable synthesis of L-allo-enduracididine from hydroxyproline derivative is described. Pyrrolidine oxidation and reductive ring opening are the key steps in the synthesis. Compared to previously reported approaches, the current route affords L-allo-enduracididine in 10 steps from 3 in 31% overall yield with >50:1 diastereoselectivity.

  DOI：

  10.1021/acs.orglett.5b02362
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 吡啶 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 30.5h， 生成 1,2-di-tert-butyl (2S,4R)-4-(methanesulfonyloxy)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  An efficient and stereospecific synthesis of (2S,4S)-2,4-diaminoglutaric acid

  摘要：

  An efficient and stereospecific synthesis of (2S,4S)-2,4-diaminoglutaric acid 1 starting from trans-4-hydroxy-L-proline 2 is presented. The key step involves the combined application of ruthenium tetroxide (RuO4) oxidation of 4-(tert-butoxycarbonylamino)proline derivatives 7 and 8 followed by regioselective ring opening of the resulting lactams 9 and 10 with 1 M LiOH. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(97)00594-6

文献信息

• Substituted saturated aza heterocycles as inhibitors of nitric oxide
  申请人：Merck & Co., Inc.

  公开号：US05821261A1

  公开（公告）日：1998-10-13

  Disclosed herein are compounds of Formula (I) ##STR1## and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These disease and disorders include hypotension, septic shock, toxic shock syndrom, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immnunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn or psoriasis and respiratory conditions such as bronchitis, asthma, and acure respiratory distress (ARDS), myocarditis, heart failure, atherosclerosis, arthritis, rheumatoid arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis. Compounds of Formula I are also useful in the treatment of hypoxia, hyperbaric oxygen convulsions and toxicity, dementia, Sydenham's chorea, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, Korsakoffs disease, imbecility related to cerebral vessel disorder, ischemic brain edema, sleeping disorders, schizophrenia, depression, PMS, anxiety, drug addiction, pain, migraine, immune complex disease, as immunosupressive agents and for preventing or reversing tolerance to opiates and diazepines.

  披露的是公式(I)化合物##STR1##及其药学上可接受的盐，发现这些化合物在治疗一氧化氮合酶介导的疾病和紊乱方面有用，包括神经退行性疾病、胃肠动力障碍和炎症。这些疾病和紊乱包括低血压、败血症休克、毒性休克综合征、血液透析、IL-2治疗（如癌症患者）、恶病质、免疫抑制（如移植治疗）、自身免疫和/或炎症迹象，包括晒伤或银屑病和呼吸系统疾病，如支气管炎、哮喘、急性呼吸窘迫综合症（ARDS）、心肌炎、心力衰竭、动脉硬化、关节炎、类风湿性关节炎、慢性或炎症性肠病、溃疡性结肠炎、克罗恩病、系统性红斑狼疮（SLE）、眼科疾病，如青光眼和葡萄膜炎、1型糖尿病、胰岛素依赖型糖尿病和囊性纤维化。公式I的化合物在治疗缺氧、高压氧惊厥和毒性、痴呆、Sydenham舞蹈病、帕金森病、亨廷顿病、肌萎缩侧索硬化、多发性硬化、科尔萨科夫病、与脑血管障碍相关的愚笨、缺血性脑水肿、睡眠障碍、精神分裂症、抑郁症、经前综合症、焦虑、药物成瘾、疼痛、偏头痛、免疫复合物疾病，作为免疫抑制剂，以及用于预防或逆转对阿片类药物和苯二氮䓬类药物的耐受性。
• A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry
  作者：J Alexander Willms、Rita Beel、Martin L Schmidt、Christian Mundt、Marianne Engeser

  DOI：10.3762/bjoc.10.211

  日期：——

  from the catalytic center in order to avoid unwanted interactions. The use of a charged catalyst leads to significantly enhanced ESI signal abundances for every catalyst-derived species which are the ones of highest interest present in a reacting solution. The new charged proline catalyst has been tested in the direct asymmetric inverse aldol reaction between aldehydes and diethyl ketomalonate. Two

  合成了一种带有带电 1-乙基吡啶鎓-4-苯氧基取代基的新型 4-羟基-L-脯氨酸衍生物，旨在促进通过 ESI 质谱法对脯氨酸催化反应进行机理研究。与中性未修饰的脯氨酸相比，带电残基确保了 ESI 响应的强烈增强。通过刚性连接体的连接将电荷标签的位置固定在远离催化中心的位置，以避免不必要的相互作用。使用带电催化剂可以显着增强每种催化剂衍生物质的 ESI 信号丰度，这些物质是反应溶液中存在的最受关注的物质。新型带电脯氨酸催化剂已在醛和酮丙二酸二乙酯之间的直接不对称逆羟醛反应中进行了测试。已检测到两种符合 List-Houk 烯胺催化机理的中间体，并通过气相裂解进行表征。此外，使用微反应器连续流技术跟踪了它们的时间演变。
• Syntheses of new conformationally constrainedS-[2-[(1-iminoethyl)amino] ethyl]homocysteine derivatives as potential nitric oxide synthase inhibitors
  作者：Lijuan J. Wang、Margaret L. Grapperhaus、Barnett S. Pitzele、Timothy J. Hagen、Kam F. Fok、Jeffrey A. Scholten、Dale P. Spangler、Mihaly V. Toth、Gina M. Jerome、William M. Moore、Pamela T. Manning、James A. Sikorski

  DOI：10.1002/hc.1109

  日期：——

  The efficient syntheses of two new types of conformationally constrained S-[2-[(1-iminoethyl)amino]ethyl]homocysteine derivatives, 1-amino-3-[2[(1-iminoethyl)amino]ethylthio]cyclobutane carboxylic Acid (5) and (4S)-4-[[2-[(1-Iminoethyl)amino]ethyl]thio]-L-proline (6), are reported. These molecules represent the first attempts to probe conformational constraint near the α-amino acid moiety of known

  两种新型构象受限的S-[2-[(1-亚氨基乙基)氨基]乙基]高半胱氨酸衍生物1-氨基-3-[2[(1-亚氨基乙基)氨基]乙硫基]环丁烷羧酸的高效合成( 5) 和 (4S)-4-[[2-[(1-亚氨基乙基)氨基]乙基]硫代]-L-脯氨酸(6)，被报道。这些分子代表了首次尝试探索已知的基于同型半胱氨酸的一氧化氮合酶抑制剂的 α-氨基酸部分附近的构象约束。目标 5 和 6 被评估为一氧化氮合酶的三种人类亚型的潜在抑制剂。© 2002 John Wiley & Sons, Inc. 杂原子化学 13:77–83, 2002; DOI 10.1002/hc.1109
• 4-(1H-1,2,3-TRIAZOL-1-YL)PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES HAVING ACTIVITY AGAINST PAIN
  申请人：ESTEVE PHARMACEUTICALS, S.A.

  公开号：EP3741750A1

  公开（公告）日：2020-11-25

  The present invention relates to 4-(1H-1,2,3-triazolyl-1-yl)pyrrolidine-2-carboxylic acid derivatives (I) having pharmacological activity towards the α2δ subunit of the voltage-gated calcium channel, to processes for the preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

  本发明涉及具有对电压门控钙通道α2δ亚基具有药理活性的4-(1H-1,2,3-三唑基-1-基)吡咯烷-2-羧酸衍生物（I），以及制备这些化合物的方法，包括它们的制药组合物和在治疗中的应用，特别是用于治疗疼痛。
• The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
  作者：Jan Pícha、Václav Vaněk、Miloš Buděšínský、Jana Mládková、Timothy A. Garrow、Jiří Jiráček

  DOI：10.1016/j.ejmech.2013.04.039

  日期：2013.7

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.