(S)-2-benzyloxy-4-(benzyloxycarbonylamino)butyric acid | 942420-52-2

• 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: (S)-2-benzyloxy-4-(benzyloxycarbonylamino)butyric acid
• 英文别名: (s)-2-Benzyloxy-4-benzyloxycarbonylaminobutyric acid；(2S)-2-phenylmethoxy-4-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 942420-52-2
• 化学式: C₁₉H₂₁NO₅
• 分子量: 343.379
• InChiKey: LTECGIVDEHBGEU-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-benzyloxy-4-(benzyloxycarbonylamino)butyric acid 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3',4',5,6-tetra-O-acetyl-3-N-[(S)-2-O-benzyl-4-(benzyloxycarbonylamino)butanoyl]-1,2',6'-triazidoneamine
  参考文献：
  名称：

  Investigation of the Regioselectivity for the Staudinger Reaction and Its Application for the Synthesis of Aminoglycosides with N-1 Modification

  摘要：

  The criteria for controlling the regioselectivity of Staudinger reduction of azides have been investigated. These findings enable a convenient direct N-1 modification of the perazidoneamine and perazidoribostamycin resulting in the synthesis of aminoglycoside antibiotics with activity against drug-resistant bacteria.

  DOI：

  10.1021/jo062588j
• 作为产物：
  描述：

  2-羟基-4-苄氧羰酰氨基丁酸 、 溴甲苯 在 barium(II) oxide 、 barium dihydroxide 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 1.78h， 生成 (S)-2-benzyloxy-4-(benzyloxycarbonylamino)butyric acid
  参考文献：
  名称：

  NOVEL AMINOGLYCOSIDE ANTIBIOTIC

  摘要：

  公开号：

  EP2036917B1

文献信息

• Synthesis and antibacterial activity of 4″ or 6″-alkanoylamino derivatives of arbekacin
  作者：Kazushige Sasaki、Yoshihiko Kobayashi、Takashi Kurihara、Yohei Yamashita、Yoshiaki Takahashi、Toshiaki Miyake、Yuzuru Akamatsu

  DOI：10.1038/ja.2015.61

  日期：2015.12

  Arbekacin, an aminoglycoside antibiotic, is an important drug because it shows a potent efficacy against methicillin-resistant Staphylococcus aureus. However, resistance to arbekacin, which is caused mainly by the bifunctional aminoglycoside-modifying enzyme, has been observed, becoming a serious problem in medical practice. To create new arbekacin derivatives active against resistant bacteria, we modified the C-4″ and 6″ positions of its 3-aminosugar portion. Regioselective amination of the 6″-position gave 6″-amino-6″-deoxyarbekacin (1), and it was converted to a variety of 6″-N-alkanoyl derivatives (6a−z). Furthermore, regioselective modifications of the 4″-hydroxyl group were performed to give 4″-deoxy-4″-epiaminoarbekacin (2) and its 4″-N-alkanoyl derivatives (12 and 13). Their antibacterial activity against S. aureus, including arbekacin-resistant bacteria, was evaluated. It was observed that 6″-amino-6″-N-[(S)-4-amino-2-hydroxybutyryl]-6″-deoxyarbekacin (6o) showed excellent antibacterial activity, even better than arbekacin.

  阿贝卡星是一种氨基糖苷类抗生素，因对耐甲氧西林的金黄色葡萄球菌显示出强效而成为重要药物。然而，由于双功能氨基糖苷修饰酶导致的耐药性已被观察到，成为医学实践中的一大难题。为了研制对耐药菌有活性新型阿贝卡星衍生物，我们对阿贝卡星的3-氨基糖部分的C-4''位点和6''位点进行了修饰。通过对6''-位置的立体选择性胺化，得到了6''-氨基-6''-脱氧阿贝卡星（1），并将其转化为各种6''-N-烷酰基衍生物（6a-z）。此外，对4''-羟基的区域选择性修饰得到了4''-脱氧-4''-表氨基阿贝卡星（2）及其4''-N-烷酰基衍生物（12和13）。评估了这些化合物对金黄色葡萄球菌（包括耐阿贝卡星的菌株）的抗菌活性。观察到6''-氨基-6''-N-[（S）-4-氨基-2-羟基丁酰基]-6''-脱氧阿贝卡星（6o）显示出优异的抗菌活性，甚至优于阿贝卡星。
• NOVEL AMINOGLYCOSIDE ANTIBIOTICS
  申请人：Kobayashi Yoshihiko

  公开号：US20120165283A1

  公开（公告）日：2012-06-28

  This invention relates to novel aminoglycoside antibiotics, which have potent antimicrobial activity against bacteria, which induce infectious diseases, particularly MRSA, and has no significant nephrotoxicity, and process for producing them. More particularly, the present invention relates to compounds represented by formula (Ia) or their pharmacologically acceptable salts or solvates, or their diastereomer mixtures, antimicrobial agents comprising them, and a process for producing them.

  这项发明涉及一种新型氨基糖苷类抗生素，对引起感染性疾病的细菌，特别是MRSA具有强效的抗菌活性，并且没有显著的肾毒性，并提供制备它们的方法。更具体地，本发明涉及由式（Ia）表示的化合物或其药理学上可接受的盐或溶剂合物，或其对映体混合物，包括它们的抗微生物剂以及制备它们的方法。
• Aminoglycoside antibiotics
  申请人：Meiji Seika Pharma Co., Ltd.

  公开号：US08148504B2

  公开（公告）日：2012-04-03

  This invention relates to novel aminoglycoside antibiotics, which have potent antimicrobial activity against bacteria, which induce infectious diseases, particularly MRSA, and has no significant nephrotoxicity, and process for producing them. More particularly, the present invention relates to compounds represented by formula (Ia) or their pharmacologically acceptable salts or solvates, or their diastereomer mixtures, antimicrobial agents comprising them, and a process for producing them.

  本发明涉及一种新型氨基糖苷类抗生素，对引起感染病的细菌，特别是MRSA具有强效的抗微生物活性，并且没有明显的肾毒性，并提供了其制备方法。更具体地，本发明涉及由式(Ia)表示的化合物或其药理学上可接受的盐或溶剂，或其对映体混合物，包含它们的抗微生物剂，以及其制备方法。
• Novel aminoglycoside antibiotics
  申请人：Kobayashi Yoshihiko

  公开号：US20090186841A1

  公开（公告）日：2009-07-23

  This invention relates to novel aminoglycoside antibiotics, which have potent antimicrobial activity against bacteria, which induce infectious diseases, particularly MRSA, and has no significant nephrotoxicity, and process for producing them. More particularly, the present invention relates to compounds represented by formula (Ia) or their pharmacologically acceptable salts or solvates, or their diastereomer mixtures, antimicrobial agents comprising them, and a process for producing them.

  本发明涉及一种新型氨基糖苷类抗生素，对引起传染病的细菌，特别是MRSA具有强效的抗微生物活性，并且没有显著的肾毒性，并提供了其生产方法。更具体地说，本发明涉及由式（Ia）表示的化合物或其药理学上可接受的盐或溶剂或其对映体混合物，包含它们的抗微生物剂以及生产它们的方法。
• Surprising Alteration of Antibacterial Activity of 5′′-Modified Neomycin against Resistant Bacteria
  作者：Jianjun Zhang、Fang-I. Chiang、Long Wu、Przemyslaw Greg Czyryca、Ding Li、Cheng-Wei Tom Chang

  DOI：10.1021/jm800997s

  日期：2008.12.11

  A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5 '' position has been developed. The structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AMEs) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AMEs allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity compared to the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert a high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that. new biological and antimicrobial activities can be obtained by chemical modifications of old drugs.