叔丁基(2S,4R)-4-羟基吡咯烷-2-羧酸酯 | 393154-87-5

• 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
• 中文名称: 叔丁基(2S,4R)-4-羟基吡咯烷-2-羧酸酯
• 英文名称: ert-butyl 4-hydroxypyrrolidine-2-carboxylate
• 英文别名: tert-butyl (2S,4R)-4-hydroxyprolinate；(2S,4R)-tert-Butyl 4-hydroxypyrrolidine-2-carboxylate；tert-butyl (2S,4R)-4-hydroxypyrrolidine-2-carboxylate
• CAS: 393154-87-5
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: VSLZXCDAPVPGOX-RQJHMYQMSA-N

物化性质

• 沸点：
  279.7±40.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  叔丁基(2S,4R)-4-羟基吡咯烷-2-羧酸酯 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 (2S,4S)-1-benzyl-2-tert-butoxycarbonylpyrrolidine-4-spiro-5'-hydantoin
  参考文献：
  名称：

  Asymmetric syntheses of all four isomers of 4-amino-4-carboxyproline: Novel conformationally restricted glutamic acid analogues

  摘要：

  Asymmetric syntheses of all four isomers of 4-amino-4-carboxyprolines, i.e. (2S,4S)-3, (2S,4R)-4, and their corresponding enantiomers, as novel conformationally restricted analogues of glutamic acid, were performed from trans-4-hydroxy-L-proline as a homochiral starting material. The key step was the spirohydantoin ring formation by employing the Bucherer-Bergs reaction of 4-oxoproline derivatives. These structures were determined by NMR studies.

  DOI：

  10.1016/0957-4166(95)00209-8
• 作为产物：
  描述：

  L-羟基脯氨酸 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 25.0h， 生成 叔丁基(2S,4R)-4-羟基吡咯烷-2-羧酸酯
  参考文献：
  名称：

  Synthesis of Conformationally Constrained DTPA Analogs. Incorporation of the Ethylenediamine Units as Aminopyrrolidines

  摘要：

  The synthesis of conformationally constrained diethylenetriaminepentaacetic acid (DTPA) analogues is an effort to probe the relationship between ligand structure and metal complex stability. In the pursuit of this objective, diastereomerically and enantiomerically pure mono- and bis-pyrrolidine analogues of DTPA have been prepared from trans-4-hydroxy-L-proline. The mono-pyrrolidine chelator 1 was constructed from a single hydroxyproline unit and an ethylenediamine moiety while two hydroxyproline-derived fragments 4e or 14b and 9b were coupled by N-alkylation of a triflate to afford the core bis-pyrrolidine structures: optically active 10 and meso-15. Deprotection of the triamine pentaesters 12 and 17 afforded the triamine pentaacetic acids 2 and 3 as their hydrochloride salts. The stereochemical homogeneity of precursor esters 12 and 17 was determined by HPLC using authentic epimeric standards to establish that essentially no racemization of the original amino acid a-center had occurred. Some loss of stereochemical homogeniety was encountered in the synthesis of 10 and 15 by N-alkylation of aminoproline 9b with a hydroxyproline-derived triflate, which had proceeded with some retention of configuration. The diastereomeric impurities were removed by crystallization of the respective benzyl carbamates. Bis-pyrrolidine pentaacids 2 and 3 formed isolable chelates with gadolinium and lutetium. A comparision of the lutetium chelates of 2 and 3 by NMR revealed significant differences which were reflective of a rigid structure with 2, while metal complexation with 3 was structurally less defined.

  DOI：

  10.1021/jo00092a022

文献信息

• Pyrrolidine derivatives
  申请人：——

  公开号：US20020049243A1

  公开（公告）日：2002-04-25

  The present invention relates to pyrrolidine derivatives and dimeric forms and/or pharmaceutically acceptable esters, and/or salts thereof. The compounds are useful as inhibitors of metalloproteases, e.g. zinc proteases, particularly zinc hydrolases, and which are effective in treating disease states are associated with vasoconstriction of increasing occurrences.

  本发明涉及吡咯烷衍生物及其二聚体形式和/或药用可接受的酯和/或盐。这些化合物可用作金属蛋白酶抑制剂，例如锌蛋白酶，特别是锌水解酶，对治疗与血管收缩增加发生相关的疾病状态有效。
• An Unconventional Redox Cross Claisen Condensation–Aromatization of 4-Hydroxyprolines with Ketones
  作者：Mi Tang、Rengwei Sun、Hao Li、Xinhong Yu、Wei Wang

  DOI：10.1021/acs.joc.7b01033

  日期：2017.8.18

  Reaction of α-amino acids, particularly prolines and their derivatives with carbonyl compounds via decarboxylative redox process, is a viable strategy for synthesis of structurally diverse nitrogen centered heterocyclics. In these processes, the decarboxylation is the essential driving force for the processes. The realization of the redox process without decarboxylation may offer an opportunity to

  α-氨基酸，特别是脯氨酸及其衍生物通过脱羧氧化还原过程与羰基化合物的反应，是合成结构多样的以氮为中心的杂环的可行策略。在这些方法中，脱羧是该方法的基本驱动力。没有脱羧的氧化还原过程的实现可能提供探索新反应的机会。在本文中，我们报道了4取代的4-羟基脯氨酸及其酯与未反应的酮发生前所未有的氧化还原Claisen型缩合芳构化级联反应的发现。我们发现使用丙酸作为催化剂和助溶剂可以改变反应过程。通常观察到的氧化还原脱羧和醛醇缩合反应显着最小化。而且，非反应性酮可有效参与克莱森缩合反应。新的反应性通过非常规的Claisen型缩合反应使氧化还原环化成为可能。由酮前体与4-取代的4-羟基脯氨酸及其酯作为亲电子酰化伙伴原位形成烯胺中间体。在反应条件下，级联反应可进行高度区域选择性和立体选择性，从而获得具有高合成和生物学价值的顺式-2,3-二氢-1 H-吡咯烷酮-1-酮，在有效的“一锅法”操作中具有广泛的底物范围，而此类结构通常需要多个步骤。
• NOVEL PROLINE DERIVATIVES
  申请人：Sánchez Rubén Alvarez

  公开号：US20100267722A1

  公开（公告）日：2010-10-21

  The invention relates to a compound of formula (I) wherein A, R 1 -R 6 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

  这项发明涉及一种化合物，其化学式为（I），其中A，R1-R6如描述和权利要求中所定义。化合物的化学式（I）可用作药物。
• Novel compounds with high therapeutic index
  申请人：Chandran Ravi V.

  公开号：US20060241017A1

  公开（公告）日：2006-10-26

  The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

  本发明涉及一种新型治疗化合物，其由氨基酸与具有羟基、氨基、羧基或酰化衍生物的药物或药物结合而成。这些高治疗指数的衍生物与它们所制备的药物具有相同的效用，并且它们具有增强的药理和制药特性。实际上，本发明的新型药物衍生物增强了至少一种治疗品质，如本文所定义。本发明还涉及含有这些化合物的制药组合物。
• [EN] BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS CIBLANT BRM ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2023096987A1

  公开（公告）日：2023-06-01

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel- Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 SMARCA2 或 BRM（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与 Von Hippel- Lindau E3 泛素连接酶结合的配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白聚集或积聚而导致的疾病或失调。