(2R,4R)-2-ethoxycarbonyl-4-hydroxypyrrolidine hydrochloride | 77449-99-1

• 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: (2R,4R)-2-ethoxycarbonyl-4-hydroxypyrrolidine hydrochloride
• 英文别名: (2R,4R)-2-(ethoxycarbonyl)-4-hydroxypyrrolidinium chloride；allo-4-cis-Hydroxy-D-proline Ethyl Ester Hydrochloride；(2R,4R)-4-hydroxyproline ethyl ester hydrochloride；allo-4-hydroxy-D-proline ethyl ester hydrochloride；cis-4-hydroxy-D-proline ethyl ester hydrochloride；ethyl (2R,4R)-4-hydroxyprolinate hydrochloride；ethyl (2R,4R)-4-hydroxy-2-pyrrolidinecarboxylate hydrochloride；ethyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate;hydrochloride
• CAS: 77449-99-1
• 化学式: C₇H₁₃NO₃*ClH
• 分子量: 195.646
• InChiKey: HHXSZDXMSRXWJV-KGZKBUQUSA-N

物化性质

• 熔点：
  138-140 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.31
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  58.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4R)-2-ethoxycarbonyl-4-hydroxypyrrolidine hydrochloride 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 (2R)-ethyl N¹-benzyl-4-oxopyrrolidine-2-carboxylate
  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 盐酸 、 乙酸酐 作用下， 反应 13.5h， 生成 (2R,4R)-2-ethoxycarbonyl-4-hydroxypyrrolidine hydrochloride
  参考文献：
  名称：

  Transition-metal-catalyzed asymmetric organic synthesis via polymer-attached optically active phosphine ligands. 5. Preparation of amino acids in high optical yield via catalytic hydrogenation

  摘要：

  DOI：

  10.1021/jo00327a023

文献信息

• RNA-selective cross-pairing of backbone-extended pyrrolidine-amideoligonucleotide mimics (bePOMs)
  作者：Roberta J. Worthington、Neil M. Bell、Raymond Wong、Jason Micklefield

  DOI：10.1039/b714580m

  日期：——

  Pyrrolidine-amide oligonucleotide mimics (POMs) can cross-pair strongly with complementary parallel and antiparallel DNA and RNA targets in a sequence-specific fashion. As a result POMs have significant potential for applications including in vivogene silencing, diagnostics and bioanalysis. To further modulate the DNA- and RNA-recognition properties and fine-tune the physiochemical properties of POMs for nucleic acid targeting, backbone-extended pyrrolidine-amideoligonucleotide mimics (bePOM I and II) were introduced. The bePOMs differ from the original POMs through the insertion of an additional methylene group into the backbone units, which increases the flexibility of the oligomers. bePOM I and II oligomers were synthesised using solid-phase peptide chemistry. Interestingly, UV thermal denaturation and circular dichroism studies reveals bePOM I and II can hybridise with complementary RNA, but not DNA.

  吡咯烷-酰胺低聚核苷酸模拟物（POMs）能够与互补的平行和反平行DNA及RNA靶标以序列特异性的方式强烈配对。因此，POMs在基因沉默、诊断和生物分析等应用方面具有显著的潜力。为了进一步调节POMs对DNA和RNA的识别特性，并微调其物理化学性质以实现核酸靶向，我们引入了骨架扩展的吡咯烷-酰胺低聚核苷酸模拟物（bePOM I和II）。bePOMs通过在骨架单元中插入一个额外的亚甲基，从而增加了寡聚物的柔韧性，与原始POMs有所不同。bePOM I和II寡聚物是通过固相肽化学合成制备的。有趣的是，紫外热变性和圆二色性研究表明，bePOM I和II能够与互补RNA杂交，但不能与DNA杂交。
• Efficient Asymmetric Hydrogenation of .ALPHA.-Amino Ketone Derivatives. A Highly Enantioselective Synthesis of Phenylephrine, Levamisole, Carnitine and Propranolol.
  作者：Shunji SAKURABA、Hisashi TAKAHASHI、Hideo TAKEDA、Kazuo ACHIWA

  DOI：10.1248/cpb.43.738

  日期：——

  The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.

  吡咯烷双膦配体（CPMs）与铑（I）形成的复合物被发现是α-氨基酮 hydrochloride 衍生物的不对称加氢反应的高效催化剂。利用这一方法，我们开发了光学活性的β-氨基醇、苯肾上腺素、左旋咪唑、肉碱和普萘洛尔的高效不对称合成。
• A Tobramycin Vector Enhances Synergy and Efficacy of Efflux Pump Inhibitors against Multidrug-Resistant Gram-Negative Bacteria
  作者：Xuan Yang、Sudeep Goswami、Bala Kishan Gorityala、Ronald Domalaon、Yinfeng Lyu、Ayush Kumar、George G. Zhanel、Frank Schweizer

  DOI：10.1021/acs.jmedchem.7b00156

  日期：2017.5.11

  paroxetine, or DBP enhances synergy and efficacy of EPIs in combination with tetracycline antibiotics against MDR Gram-negative bacteria including Pseudomonas aeruginosa. Besides potentiating tetracycline antibiotics, TOB–EPI conjugates can also suppress resistance development to the tetracycline antibiotic minocycline, thereby providing a strategy to develop more effective adjuvants to rescue tetracycline

  药物外排机制与革兰氏阴性细菌的外膜通透性屏障协同相互作用，导致内在抗性，这对抗生素药物开发提出了重大挑战。阻止抗生素流出的外排泵抑制剂（EPI）可以使抗生素协同作用，但是治疗多药耐药（MDR）革兰氏阴性感染的EPI /抗生素联合疗法的临床开发一直具有挑战性。这部分是由于目前的EPI不能有效地穿透外膜和抵抗外排所致。我们证明，妥布霉素（TOB）载体与EPI（如NMP，帕罗西汀或DBP）的缀合可增强EPI与四环素抗生素联合抗MDR革兰氏阴性细菌（包括铜绿假单胞菌）的协同作用和功效。除增强四环素抗生素外，TOB-EPI偶联物还可以抑制对四环素抗生素米诺环素的耐药性发展，从而提供了一种策略，可开发出更有效的佐剂，从MDR革兰氏阴性细菌的耐药性中拯救四环素抗生素。
• Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives
  作者：D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、P. Remuzon、A. Weber、T. Oki、M. Masuyoshi

  DOI：10.1021/jm00167a010

  日期：1990.5

  A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed

  已经制备了许多7-取代的1-叔丁基-6-氟喹诺酮-3-羧酸和7-取代的1-叔丁基-6-氟-1,8-萘啶-3-羧酸。经测试具有抗菌活性。其中7-氨基吡咯烷基20b和7-二氮杂双环萘啶18b是体外和体内最有效的化合物。还讨论了理化数据和急性毒性。考虑到体外和体内的微生物活性，低毒性和药代动力学特征，化合物18b BMY 40062表现出最有利的总体性能，并被选择用于临床评估。
• 5,11-dihydrodibenzo[b,e][1,4]oxazepine derivatives and pharmaceutical
  申请人：Ajinomo Co., Inc.

  公开号：US06127361A1

  公开（公告）日：2000-10-03

  Disclosed are 5,11-Dihydrodibenzo[b,e][1,4]oxazepine derivatives such as (R)-(+)-5,11-dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenz o[b,e][1,4]oxazepine and (R)-(+)-5,11-dihydro-5-[1-(4-fluorophenethyl)-2-pyrrolidinylmethyl]dibenzo [b,e][1,4]oxazepine, stereoisomers thereof, pharmacologically acceptable salts thereof, or hydrates thereof and a phramaceutical composition conating the 5,11-Dihydrodibenzo[b,e][1,4]oxazepine derivatives. The derivatives have an excellent activity of improving a digestive tract moving function and are free of side effect.

  揭示了5,11-二氢二苯并[b,e][1,4]噁唑啶衍生物，例如(R)-(+)-5,11-二氢-5-[1-(4-甲氧基苯乙基)-2-吡咯啶甲基]二苯并[b,e][1,4]噁唑啶和(R)-(+)-5,11-二氢-5-[1-(4-氟苯乙基)-2-吡咯啶甲基]二苯并[b,e][1,4]噁唑啶，它们的立体异构体，相应的药理学可接受的盐，或水合物，以及含有这些5,11-二氢二苯并[b,e][1,4]噁唑啶衍生物的药物组合物。这些衍生物具有改善消化道运动功能的出色活性，并且没有副作用。