penta-N-Cbz-paromomycin | 55728-88-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: penta-N-Cbz-paromomycin
• 英文别名: N,N'-bis-benzyloxycarbonyl-O⁴-(2-benzyloxycarbonylamino-α-D-2-deoxy-glucopyranosyl)-O⁵-[O³-(2,6-bis-benzyloxycarbonylamino-β-L-2,6-dideoxy-idopyranosyl)-β-D-ribofuranosyl]-1D-2-deoxy-streptamine；benzyl N-[(1S,2R,3R,4S,5R)-2-[(2S,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(phenylmethoxycarbonylamino)oxan-2-yl]oxy-3-[(2S,3R,4S,5R)-4-[(2R,3R,4R,5S,6S)-4,5-dihydroxy-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4-hydroxy-5-(phenylmethoxycarbonylamino)cyclohexyl]carbamate
• CAS: 55728-88-6
• 化学式: C₆₃H₇₅N₅O₂₄
• 分子量: 1286.31
• InChiKey: ZHHAYKKMPZUFGF-PHQTXDRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  92
• 可旋转键数：
  29
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  409
• 氢给体数：
  13
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  penta-N-Cbz-paromomycin 在 sodium hydroxide 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 C₆₇H₈₁N₅O₂₄
  参考文献：
  名称：

  6-Hydroxy to 6‴-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3′)-IIIa kinase

  摘要：

  Based on molecular modeling and available X-ray structure data on aminoglycosides complexed with a bacterial ribosomal surrogate or with a kinase, two analogues of paromomycin were prepared by tethering the 6-OH and the 6"'-NH2 group with a five-carbon bridge. Only one of two possible hydroxyl groups was phosphorylated by the kinase. The application of ring closure metathesis is presented for the first time to construct bridged macrocyclic analogues in the aminoglycoside series. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.014
• 作为产物：
  描述：

  硫酸巴龙霉素 、 氯甲酸苄酯 在 sodium carbonate 、 三乙胺 作用下， 以 水 、 甲醇 为溶剂， 反应 59.0h， 生成 penta-N-Cbz-paromomycin
  参考文献：
  名称：

  [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
  [FR] ANALOGUES D'AMINOGLYCOSIDE ANTIBACTÉRIENS

  摘要：

  揭示了具有抗菌活性的化合物。这些化合物具有以下结构（I）：（I）包括立体异构体、药学上可接受的盐和前药，其中Q1、Q2、R1、R2和R3如本文所定义。还公开了与制备和使用这些化合物相关的方法，以及包含这些化合物的药物组合物。

  公开号：

  WO2010042851A1

文献信息

• ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
  申请人：Goldblum Adam Aaron

  公开号：US20120122809A1

  公开（公告）日：2012-05-17

  Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Q 1 and Q 2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  揭示了具有抗菌活性的化合物。这些化合物具有以下结构（I）：包括立体异构体、前药和其药用可接受的盐，其中Q1和Q2如本文所定义。还公开了与制备和使用这些化合物相关的方法，以及包含这些化合物的药物组合物。
• Aminoglycoside antibiotics: The formation and characterization of dihydrooxazine derivatives in the paromomycin series
  作者：Stephen Hanessian、Robert Massé、Goran Ekborg

  DOI：10.1139/v78-243

  日期：1978.6.1

  Treatment of penta-N-benzyloxycarbonylparomomycin with benzaldehyde and excess zinc chloride gives a dibenzylidene derivative in high yield. This consists of the 4′,6′-O-benzylidene 4′′′,6′′′-N,O-benzylidene (dihydrooxazine) derivative of penta-N-benzyloxycarbonylparomomycin. Chemical evidence is presented to support this structure and model studies are reported for the formation of dihydrooxazine and oxazolidine derivatives of benzyloxycarbonylamino sugars containing suitably situated hydroxyl groups. The easily obtained dihydrooxazine derivative of paromomycin constitutes an interesting, preferentially blocked derivative, that is useful for the chemical modification of the parent antibiotic.

  对五重N-苄氧羰基帕罗莫霉素进行苯甲醛和过量氯化锌处理，可以高产得到二苄亚甲基衍生物。这包括五重N-苄氧羰基帕罗莫霉素的4′，6′-O-苄亚甲基4′′′，6′′′-N，O-苄亚甲基（二氢噁唑）衍生物。化学证据支持这种结构，并报道了模型研究，以形成含有适当位置羟基的苄氧羰基氨基糖的二氢噁唑和噁唑烷衍生物。易于获得的帕罗莫霉素二氢噁唑衍生物是一种有趣的、优先阻断的衍生物，可用于对亲本抗生素进行化学修饰。
• Robust polymeric nanoparticles for the delivery of aminoglycoside antibiotics using carboxymethyldextran-b-poly(ethyleneglycols) lightly grafted with n-dodecyl groups
  作者：Ghareb M. Soliman、Janek Szychowski、Stephen Hanessian、Françoise M. Winnik

  DOI：10.1039/c0sm00316f

  日期：——

  Aminoglycoside antibiotics are effective in the treatment of infections caused by aerobic Gram negative bacilli, but their widespread use is hampered by serious side effects that may be alleviated through the use of tailored delivery systems. Robust polyion complex (PIC) micelles, incorporating up to 50 weight % drug, were prepared using two aminoglycosides: paromomycin and neomycin, and a dihydrophilic block copolymer consisting of a poly(ethyleneglycol) (PEG) chain linked to a carboxymethyldextran fragment (CMD) lightly grafted with n-dodecyl groups. The micelles were stable under physiological conditions (pH 7.4, 150 mM NaCl), in contrast to micelles formed by the unmodified CMD-PEG and the aminoglycosides or their guanidinylated derivatives. The aminoglycosides were released from the n-dodecyl-CMD-PEG micelles in a pharmacologically active form as indicated by their ability to kill test micro-organisms in culture. This study opens up new opportunities in the biomedical applications of PIC micelles with inherently enhanced stability.

  氨基糖苷类抗生素可有效治疗需氧革兰阴性杆菌引起的感染，但严重的副作用阻碍了其广泛应用，而通过使用定制的给药系统则可减轻副作用。本研究使用两种氨基糖苷类药物：帕罗霉素和新霉素，以及一种二亲水嵌段共聚物制备了含有高达 50% 重量百分比药物的强效多离子复合物（PIC）胶束，该共聚物由聚乙二醇（PEG）链和轻度接枝正十二烷基的羧甲基二葡聚糖片段（CMD）组成。这种胶束在生理条件下（pH 7.4，150 mM NaCl）是稳定的，这与未改性的 CMD-PEG 和氨基糖苷类或其胍基化衍生物形成的胶束形成鲜明对比。从正十二烷基-CMD-PEG 胶束中释放出的氨基糖苷具有药理活性，这体现在它们能够杀死培养中的试验微生物。这项研究为具有内在增强稳定性的 PIC 胶束的生物医学应用提供了新的机遇。
• Hybrid Aminoglycoside Antibiotics <i>via</i> Tsuji Palladium-Catalyzed Allylic Deoxygenation
  作者：Stephen Hanessian、Juan Pablo Maianti、Rowena D. Matias、Lee Ann Feeney、Eliana S. Armstrong

  DOI：10.1021/ol2027703

  日期：2011.12.16

  Biosynthetically inspired manipulation of the antibiotic paromomycin led, in six high-yielding steps, to a ring A harboring an alpha,beta-unsaturated 6'-aldehyde and an allylic 3'-methylcarbonate group. Tsuji deoxygenation in the presence of 5 mol % Pd-2(dba)(3) and Bu3P granted access to a novel series of 3',4'-dideoxy-4',5'-dehydro ring A hybrids. The neomycin-sisomicin hybrid exhibited superior in vitro antibacterial activity to the parent compound neomycin.
• WO2008/124821
  申请人：——

  公开号：——

  公开（公告）日：——