1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A | 5605-66-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A
• 英文别名: tetrakis(N-benzyloxycarbonyl)kanamycin A；tetra-N-(benzyloxycarbonyl)-kanamycin A；tetra N-benzyloxycarbonyl-kanamycin A；Cbz₄-kanamycin；per-N-Cbz-kanamycin A；1L-N,N'-bis-benzyloxycarbonyl-O⁴-(3-benzyloxycarbonylamino-α-D-3-deoxy-glucopyranosyl)-O⁶-(6-benzyloxycarbonylamino-α-D-6-deoxy-glucopyranosyl)-2-deoxy-streptamine；benzyl N-[(2S,3R,4S,5S,6R)-3,5-dihydroxy-2-[(1S,2R,3R,4S,6R)-2-hydroxy-4,6-bis(phenylmethoxycarbonylamino)-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxycyclohexyl]oxy-6-(hydroxymethyl)oxan-4-yl]carbamate
• CAS: 5605-66-3
• 化学式: C₅₀H₆₀N₄O₁₉
• 分子量: 1021.04
• InChiKey: AIDXZJAAGUGGHO-OHUKVWCVSA-N

物化性质

• 溶解度：
  溶于DMF、DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  73
• 可旋转键数：
  22
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  332
• 氢给体数：
  11
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 以78%的产率得到1,3,6'-tri-N-benzyloxycarbonyl-kanamycin A
  参考文献：
  名称：

  Selective modification of the 3′′-amino group of kanamycin prevents significant loss of activity in resistant bacterial strains

  摘要：

  卡那霉素A抗生素中的N-3''修饰可以防止在耐药细菌菌株中发生显著的活性丧失。

  DOI：

  10.1039/c5ob01599e
• 作为产物：
  描述：

  苯甲氧羰酰琥珀酰亚胺 、 卡那霉素二硫酸盐 在 碳酸氢钠 作用下， 以 水 为溶剂， 生成 1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A
  参考文献：
  名称：

  Synthesis, separation, and characterization of amphiphilic sulfated oligosaccharides enabled by reversed-phase ion pairing LC and LC–MS methods

  摘要：

  Synthesis of amphiphilic oligosaccharides is problematic because traditional methods for separating and purifying oligosaccharides, including sulfated oligosaccharides, are generally not applicable to working with amphiphilic sugars. We report here RPIP-LC and LC-MS methods that enable the synthesis, separation, and characterization of amphiphilic N-arylacyl O-sulfonated aminoglycosides, which are being pursued as small-molecule glycosaminoglycan mimics. The methods described in this work for separating and characterizing these amphiphilic saccharides are further applied to a number of uses: monitoring the progression of sulfonation reactions with analytical RP-HPLC, characterizing sulfate content for individual molecules with ESI-MS, determining the degree of sulfation for products having mixed degrees of sulfation with HPLC and LC-MS, and purifying products with benchtop C18 column chromatography. We believe that the methods described here will be broadly applicable to enabling the synthesis, separation, and characterization of amphiphilic, sulfated, and phosphorylated oligosaccharides and other types of molecules substituted to varying degrees with both anionic and hydrophobic groups. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.09.020

文献信息

• A highly selective N-protection strategy for the preparation of 1-N-alkylated kanamycin antibiotics
  作者：Michael B. Thomas、Michael T. Williams

  DOI：10.1016/s0040-4039(00)71171-3

  日期：1980.1

  An O to N acyl migration technique has been used to selectively acetylate the amino groups of the aminosugar rings of kanamycins A and B, leaving the amino groups on the 2-deoxy-streptamine ring unprotected. A formylation-deformylation process then converts these N-acetylated kanamycins to their 3-N-formyl derivatives with high regioselectivity, giving key intermediates for the efficient preparation

  已经使用O到N酰基转移技术来选择性地乙酰化卡那霉素A和B的氨基糖环的氨基，而使2-脱氧-链胺胺环上的氨基未被保护。然后，甲酰化-甲酰化过程将这些N-乙酰化的卡那霉素以高区域选择性转化为它们的3-N-甲酰基衍生物，为有效制备1-N-烷基化的卡那霉素提供了关键的中间体。
• Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide
  作者：Anna Brezden、Mohamed F. Mohamed、Manish Nepal、John S. Harwood、Jerrin Kuriakose、Mohamed N. Seleem、Jean Chmielewski

  DOI：10.1021/jacs.6b04831

  日期：2016.8.31

  antimicrobial activity of the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate effectively cleared intracellular pathogenic bacteria within macrophages more potently than that of a conjugate lacking the disulfide moiety. Notably, successful clearance of Mycobacterium tuberculosis within macrophages was observed with the dual antibiotic conjugate, and Salmonella levels were significantly

  由细胞内病原体（如分枝杆菌、沙门氏菌和布鲁氏菌）引起的细菌感染是一种迅速发展的全球健康流行病，需要采取紧急行动。然而，许多抗生素（包括氨基糖苷类）对细胞内病原菌的治疗价值由于它们不能穿过真核细胞膜而受到损害。为了解决这个重大问题，制备了抗生素卡那霉素和非膜溶解性广谱抗菌肽的可裂解偶联物，具有有效的哺乳动物细胞渗透能力，P14LRR。这种方法允许卡那霉素作为偶联物进入哺乳动物细胞，通过系链连接，在细胞内的还原环境中分解。P14KanS 偶联物的强效抗菌活性在体外得到证实，并且这种可还原的结合物比缺乏二硫键部分的结合物更有效地清除巨噬细胞内的细胞内病原菌。值得注意的是，使用双重抗生素偶联物观察到巨噬细胞内结核分枝杆菌的成功清除，并且在体内秀丽隐杆线虫模型中沙门氏菌水平显着降低。
• Structural Studies on the Cyclic Carbamate Derivatives of Kanamycin A
  作者：Yasushi Takagi、Chikara Komuro、Tsutomu Tsuchiya、Sumio Umezawa

  DOI：10.1246/bcsj.54.1834

  日期：1981.6

  tetrakis(N-benzyloxycarbonyl)-6″-O-tritylkanamycin A with sodium hydride in N,N-dimethyl-formamide, followed by chromatography, afforded 4′,6′ : 3″,4″-, and 4′,6′ : 2″,3″-bis(cyclic carbamate) and 3″,4″-and 2″,3″-mono(cyclic carbamate) (2, 3, and others). The structures of the position isomers 2 and 3 were determined by the NMR spectra at 500 MHz of their N-tosyl-O-acetyl derivatives.

  在 N,N-二甲基甲酰胺中用氢化钠处理四 (N-苄氧羰基)-6"-O-三苯甲基链霉素 A，然后进行色谱分析，得到 4',6': 3",4"-, 和 4', 6' : 2",3"-双（环状氨基甲酸酯）和 3",4"-和 2",3"-单（环状氨基甲酸酯）（2、3 和其他）。位置异构体 2 和 3 的结构由它们的 N-甲苯磺酰基-O-乙酰基衍生物在 500 MHz 下的 NMR 光谱确定。
• Synthesis of 6″-Modified Kanamycin A Derivatives and Evaluation of Their Antibacterial Properties
  作者：Kseniya Shapovalova、Georgy Zatonsky、Natalia Grammatikova、Ilya Osterman、Elizaveta Razumova、Andrey Shchekotikhin、Anna Tevyashova

  DOI：10.3390/pharmaceutics15041177

  日期：——

  the ability of the tetra-N-protected-6″-O-(2,4,6-triisopropylbenzenesulfonyl)kanamycin A to interact with a weak nucleophile, pyridine, resulting in the formation of the corresponding pyridinium derivative. Introducing small diamino-substituents at the 6″-position of kanamycin A did not significantly alter the antibacterial activity of the parent antibiotic, but further modification by acylation resulted

  氨基糖甙类抗生素是最早应用于临床的一类抗生素，至今仍在使用。它们具有广泛的抗菌活性，使它们能够有效对抗许多不同类型的细菌。尽管它们的使用历史悠久，但氨基糖苷类仍然被认为是开发新型抗菌剂的有前途的支架，特别是当细菌继续对现有抗生素产生耐药性时。我们合成了一系列具有额外可质子化基团（氨基、胍基或吡啶鎓）的 6″-脱氧卡那霉素 A 类似物，并测试了它们的生物活性。我们首次证明了 tetra-N-protected-6″-O-(2,4,6-triisopropylbenzenesulfonyl)kanamycin A 与弱亲核试剂吡啶相互作用的能力，导致形成相应的吡啶鎓衍生物。在卡那霉素 A 的 6”位引入小的二氨基取代基并没有显着改变母体抗生素的抗菌活性，但通过酰化进一步修饰导致抗菌活性完全丧失。然而，引入胍残基导致化合物对金黄色葡萄球菌的活性有所提高。此外，与母体卡那霉素 A 相比，大多数获得的
• Selective Inhibition of Bacterial and Human Topoisomerases by <i>N</i>-Arylacyl <i>O</i>-Sulfonated Aminoglycoside Derivatives
  作者：Amanda M. Fenner、Lisa M. Oppegard、Hiroshi Hiasa、Robert J. Kerns

  DOI：10.1021/ml3004507

  日期：2013.5.9

  Numerous therapeutic applications have been proposed for molecules that bind heparin-binding proteins. Development of such compounds has primarily focused on optimizing the degree and orientation of anionic groups on a scaffold, but utility of these polyanions has been diminished by their typically large size and nonspecific interactions with many proteins. In this study, N-arylacyl O-sulfonated aminoglycosides were synthesized and evaluated for their ability to selectively inhibit structurally similar bacterial and human topoisomerases. It is demonstrated that the structure of the aminoglycoside and of the N-arylacyl moiety imparts selective inhibition of different topoisomerases and alters the mechanism. The results here outline a strategy that will be applicable to identifying small, structurally defined oligosaccharides that bind heparin-binding proteins with a high degree of selectivity.