3,6'-bis(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)kanamycin A | 74256-73-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,6'-bis(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)kanamycin A
• 英文别名: 3,6'-bis-N-benzyloxycarbonyl-3"-N-trifluoroacetyl kanamycin A；3,6'-di(N-benzyloxycarbonyl)-3''-N-(trifluoroacetyl)kanamycin A；benzyl N-[[(2R,3S,4S,5R,6R)-6-[(1R,2R,3S,4R,6S)-4-amino-3-[(2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2,2,2-trifluoroacetyl)amino]oxan-2-yl]oxy-2-hydroxy-6-(phenylmethoxycarbonylamino)cyclohexyl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl]carbamate
• CAS: 74256-73-8
• 化学式: C₃₆H₄₇F₃N₄O₁₆
• 分子量: 848.782
• InChiKey: BAOCREOZMQNTJA-SUMSFFDGSA-N

物化性质

• 沸点：
  1055.3±65.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.64
• 重原子数：
  59.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  310.31
• 氢给体数：
  11.0
• 氢受体数：
  17.0

反应信息

• 作为反应物：
  描述：

  3,6'-bis(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)kanamycin A 在 palladium on activated charcoal ammonium hydroxide 、 四丁基氟化铵 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 溶剂黄146 为溶剂， 反应 63.0h， 生成
  参考文献：
  名称：

  Probing the functional requirements of the l-haba side-chain of amikacin—synthesis, 16S A-site rRNA binding, and antibacterial activity

  摘要：

  The 1-amino group in amikacin was acylated with a variety of 2-hydroxy aminocarboxylic acids to probe the effect of acylation on ribosomal binding and antibacterial activity. The N-hydroxy urea analogue of amikacin (8a) in which the 2-S-hydroxyl-bearing carbon was replaced by an N-OH group was equally active against S. aureus and E. coli in vitro. The analogous tobramycin variant 9 was more active than amikacin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01625-3
• 作为产物：
  描述：

  卡那霉素碱 在 zinc diacetate 作用下， 以 二甲基亚砜 为溶剂， 生成 3,6'-bis(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)kanamycin A
  参考文献：
  名称：

  共价连接的卡那霉素-环丙沙星混合抗生素作为抵抗细菌耐药性的工具。

  摘要：

  为了解决日益增长的抗生素耐药性问题，合成了一组共价连接氟喹诺酮（环丙沙星）和氨基糖苷（卡那霉素A）抗生素的12种杂合化合物，并确定了它们对革兰氏阴性和革兰氏阳性细菌的活性，包括耐药性株。杂种相对于环丙沙星具有拮抗作用，但相对于亲本卡那霉素对革兰氏阴性细菌的效力要强得多，并且克服了对氨基糖苷类的最主要的抗性机制。选定的杂种是细菌蛋白合成抑制剂的效果比亲代卡那霉素低42-640倍，而它们显示出与环丙沙星类似的对DNA促旋酶和拓扑异构酶IV酶的抑制活性。杂种在两个大肠杆菌中均显示出明显的抗性发育延迟。大肠埃希菌和枯草芽孢杆菌与单独的成分药物或其1：1混合物相比。更一般地，数据表明氨基糖苷-氟喹诺酮杂化物的拮抗组合可以导致减慢/防止耐药性出现的新化合物。

  DOI：

  10.1016/j.bmc.2017.02.068

文献信息

• Conjugated antimicrobial agents
  申请人：Technion Research & Development Foundation Limited

  公开号：US09149536B2

  公开（公告）日：2015-10-06

  Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

  本文提供了两种抗生素的抗菌结合物，展现出对抗耐药细菌的改善活性，相比单独使用每种抗生素或它们的混合物，并且基本上没有产生抗性，以及制备这些结合物的过程、含有这些结合物的组合物，以及在医疗治疗中对抗病原微生物的用途。所披露的抗菌结合物由氨基糖苷类和非核糖体活性抗生素组成。其中一些抗菌结合物是通过“click”化学方法制备的。
• Study on fluorination-toxicity relationships. Syntheses of 1-N-[(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl] derivatives of kanamycins
  作者：Yoshiaki Takahashi、Chiga ueda、Tsutomu Tsuchiya、Yoshihiko Kobayashi

  DOI：10.1016/0008-6215(93)84060-j

  日期：1993.10

  (2R,3R)- And (2R,3S)-4-azido-3-fluoro-2-hydroxybutanoic acids (11 and 22) have been prepared from 3-deoxy-3-fluoro-1,2-0-isopropylidene-a-D-glucofuranose (1) and 3,5-di-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose (12), respectively. They were then coupled to the H2N-1 group of suitably protected kanamycin A or kanamycin B analogs to give, 1-N-[(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl]kanamycins (32-35). This group of compounds (32-34) exhibited similar antibacterial activity and toxicity level as those of the corresponding 1-N-[(S)-4-amino-2-hydroxybutanoyl] (AHB) derivatives of kanamycins. The base strength of the H2N-4''' group of 32 and 34, as determined by C-13 NMR spectroscopy (in D2O) at varying pD values, was found to be lower when compared to the basicity for the corresponding AHB analogs. The relationship between observed toxicity and base strength of the H2N-4''' group is discussed.

  (2R,3R)-和(2R,3S)-4-叠氮-3-氟-2-羟基丁酸(11和22)分别由3-去氧-3-氟-1,2-O-异丙叉基-a-D-古洛吡喃糖(1)和3,5-二-O-苯甲基-1,2-O-异丙叉基-a-D-木糖吡喃糖(12)制备。随后，它们被连接到适当保护的卡那霉素A或卡那霉素B类似物的H2N-1基团上，生成1-N-[(2R,3R)-和(2R,3S)-4-氨基-3-氟-2-羟基丁酰]卡那霉素(32-35)。该类化合物(32-34)表现出与卡那霉素对应1-N-[(S)-4-氨基-2-羟基丁酰](AHB)衍生物相似的抗菌活性和毒性水平。通过C-13核磁共振光谱(在D2O中，不同pD值测定)， -4'''基团(32和34)的碱性强弱与对应的AHB类似物相比较低。观察到的毒性和 -4'''基团的碱强度之间的关系进行了讨论。
• Syntheses of 1-Epikanamycin A and Its 1-<i>N</i>-[(<i>S</i>)-4-Amino-2-hydroxybutyryl] Derivative
  作者：Yoshiaki Takahashi、Tsutomu Tsuchiya、Yukiko Suzuki、Sumio Umezawa、Hamao Umezawa、Shunzo Fukatsu

  DOI：10.1246/bcsj.56.1807

  日期：1983.6

  The titled compounds were prepared from 3,6′-bis(N-benzyloxycarbonyl)-3″-N-(trifluoroacetyl)kanamycin A (1). Oxidation of 1 with hydrogen peroxide in the presence of sodium tungstate gave the 1-hydroxyimino derivative, which, after deblocking, gave 1-deamino-1-dehydro-1-hydroxyiminokanamycin A (6). Reduction of 6 with Raney nickel–hydrogen in aqueous ammonia gave a mixture of kanamycin A and 1-epikanamycin A (9), which were separated through derivation to the corresponding tetrakis-N-(t-butoxycarbonyl) derivatives, which showed different solubility in chloroform. 1-N-[(S)-4-Amino-2-hydroxybutyryl]-1-epikanamycin A was prepared from 9 by the zinc acetate–ethyl trifluoroacetate method [to give 3,6′-bis(N-benzyloxycarbonyl)-1-epi-3″-trifluoroacetamidokanamycin A] followed by a regiospecific 1-N-acylation with (S)-4-benzyloxycarbonylamino-2-hydroxybutyryl group and successive deblocking.

  标题化合物由 3,6′-双（N-苄氧羰基）-3″-N-（三氟乙酰基）卡那霉素 A（1）制备而成。在钨酸钠存在下，用过氧化氢氧化 1，得到 1-羟基亚氨基衍生物，脱锁后得到 1-脱氨基-1-脱氢-1-羟基亚氨基卡那霉素 A（6）。在氨水中用 Raney 镍氢还原 6，得到卡那霉素 A 和 1-epikanamycin A 的混合物（9），通过衍生分离出相应的四-N-（t-丁氧羰基）衍生物，它们在氯仿中的溶解度不同。1-N-[(S)-4-氨基-2-羟基丁酰基]-1-表卡那霉素 A 由 9 通过醋酸锌-三氟乙酸乙酯法制备[得到 3、6′-双(N-苄氧羰基)-1-表-3″-三氟乙酰氨基卡那霉素 A]，然后与(S)-4-苄氧羰基氨基-2-羟基丁酰基进行区域特异性 1-N-酰化，并连续脱锁。
• ZAXARIEVA, ANI TSVETKOVA;ZHELEVA, ANNA BORISOVA;MIXAJLOV, VENTSEL GEORGIE+
  作者：ZAXARIEVA, ANI TSVETKOVA、ZHELEVA, ANNA BORISOVA、MIXAJLOV, VENTSEL GEORGIE+

  DOI：——

  日期：——
• UMEHDZAVA, SUMIO;TSUTIYA, OSAMU;TAKEH, TOMIO;UMEHDZAVA, KADZUO;TAKAXASI, +
  作者：UMEHDZAVA, SUMIO、TSUTIYA, OSAMU、TAKEH, TOMIO、UMEHDZAVA, KADZUO、TAKAXASI, +

  DOI：——

  日期：——