tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyprolinate | 194163-83-2

• 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: tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyprolinate
• 英文别名: di-tert-butyl (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate；1,2-DI-Tert-butyl (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate；ditert-butyl (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate
• CAS: 194163-83-2
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: OXHIVNUWGSCHBD-UWVGGRQHSA-N

物化性质

• 熔点：
  53-55 °C
• 沸点：
  369.1±42.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyprolinate 在 吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-thioacetoxyprolinate
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.04.039
• 作为产物：
  描述：

  (4S)-1-(tert-butyloxycarbonyl)-4-(p-nitrobenzoyloxy)-L-proline tert-butyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyprolinate
  参考文献：
  名称：

  Substituted saturated aza heterocycles as inhibitors of nitric oxide

  摘要：

  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。

  公开号：

  US05821261A1

文献信息

• Automated Radiosynthesis of <i>cis</i>- and <i>trans</i>-4-[¹⁸F]Fluoro-<scp>l</scp>-proline Using [¹⁸F]Fluoride
  作者：Timaeus E. F. Morgan、Leanne M. Riley、Adriana A. S. Tavares、Andrew Sutherland

  DOI：10.1021/acs.joc.1c00755

  日期：2021.10.15

  detection of numerous diseases such as pulmonary fibrosis and various carcinomas. These imaging agents are typically prepared by nucleophilic fluorination of 4-hydroxy-l-proline derivatives, with [18F]fluoride, followed by deprotection. Although effective radiofluorination reactions have been developed, the overall radiosynthesis process is suboptimal due to deprotection methods that are performed manually

  正电子发射断层扫描成像剂顺式和反式-4-[ 18 F]氟-l-脯氨酸用于检测多种疾病，例如肺纤维化和各种癌症。这些成像剂通常通过用[ 18 F]氟化物对4-羟基-1-脯氨酸衍生物进行亲核氟化，然后脱保护来制备。尽管已经开发出有效的放射性氟化反应，但由于手动执行的去保护方法、需要多个步骤或涉及恶劣条件，整个放射合成过程并不是最理想的。在这里，我们描述了两种合成路线的开发，这些路线允许获得前体，这些前体在温和的酸性条件下经历高度选择性的放射性氟化反应和快速脱保护。人们发现这些方法与自动化兼容，避免了放射性中间体的手动处理。
• Synthesis of (2S,3R)- and (2S,3S)-[3-2H1]-proline via highly stereoselective hydrolysis of a silyl enol ether
  作者：Paul Barraclough、Caroline A. Spray、Douglas W. Young

  DOI：10.1016/j.tetlet.2005.04.126

  日期：2005.7

  A straightforward synthesis of (2S)-[3,3-2H2]-proline 1c and (2S,3R)- and (2S,3S)-[3-2H1]-proline, 1b and 1a, respectively, has been devised. The key step of the route to the latter compounds involves highly stereoselective hydrolysis of the silyl enol ethers 3 and 3a, respectively, with protonation (deuteriation) from the re-face of the silyl enol ether.

  （2 S）-[3,3- 2 H 2 ]-脯氨酸1c和（2 S，3 R）-和（2 S，3 S）-[3- 2 H 1 ]-脯氨酸1b的直接合成已经分别设计了1a和1a。后者化合物的路线的关键的步骤涉及高度立体选择性水解的甲硅烷基烯醇醚3和3a中从分别与质子化（deuteriation）重的甲硅烷基烯醇醚-面。
• Two separate and distinct syntheses of stereospecifically deuteriated samples of (2S)-proline
  作者：Paul Barraclough、Petra Dieterich、Caroline A. Spray、Douglas W. Young

  DOI：10.1039/b601097k

  日期：——

  were then converted into (2S,3S)-[3-(2)H1]- and (2S,3R)-[2,3-(2)H2]-proline, 1a and 1b respectively. The second synthesis provides (2S)-[3,3-(2)H2]-, (2S,3S)- and (2S,3R)-[3-(2)H1]-proline, 1d, 1a and 1c respectively, and has as its key step the highly stereoselective hydrolysis of the silylenol ethers 14 and 14a respectively in which deuteriation or protonation occurs from the re-face of the enol ether

  报道了在β-碳原子上立体定向氘化的氨基酸L-脯氨酸样品的两种不同的合成。在这些方法中的第一方法中，通过化学-酶促合成制备的标记的重氮酮6已经在碱性条件下被光解，以通过水解和分子内捕集所得的烯酮中间体9而得到相应的标记的焦谷氨酸甲酯10。然后将它们转化为（2S，3S）-[3-（2）H1]-和（2S，3R）-[2，3-（2）H2]-脯氨酸，分别为1a和1b。第二种合成分别提供（2S）-[3,3-（2）H2]-，（2S，3S）-和（2S，3R）-[3-（2）H1]-脯氨酸，1d，1a和1c ，并且是关键步骤的甲硅烷基醚14和14a的高度立体选择性水解，其中从烯醇醚的表面发生氘化或质子化。
• [EN] INHIBITORS OF AMINO ACID TRANSPORT<br/>[FR] INHIBITEURS DU TRANSPORT D'ACIDES AMINÉS
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2022087630A1

  公开（公告）日：2022-04-28

  Disclosed herein are compounds and compositions of formula (I) that are inhibitors of amino acid transport, specifically alanine serine cysteine transporter 2 (ASCT2): These compounds are useful as therapeutic agents for treating various cancers. Methods for inhibiting an ASCT2 transporter are also disclosed. Certain compounds are selective for an ASCT transporter.

  本文公开了式（I）的化合物和组合物，它们是氨基酸转运抑制剂，特别是丙氨酸/丝氨酸/半胱氨酸转运蛋白2（ASCT2）的抑制剂：这些化合物可用作治疗各种癌症的治疗剂。还公开了抑制ASCT2转运蛋白的方法。某些化合物对ASCT转运蛋白具有选择性。
• Phosphonate compounds for treatment of medical disorders
  申请人：Achillion Pharmaceuticals, Inc.

  公开号：US10000516B2

  公开（公告）日：2018-06-19

  Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.

  提供了包含式 I 或其药学上可接受的盐或组合物（其中 A 基上的 R12 或 R13 是膦酸盐取代基 (R32)）的补体因子 D 抑制剂的化合物、使用方法和制造工艺。本文所述的抑制剂以因子 D 为靶点，抑制或调节补体级联。本文所述的因子 D 抑制剂可减少补体的过度活化。