核糖霉素 | 25546-65-0

• 物质功能分类: 原料药 - 抗生素类药物 - 氨基糖苷类药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 核糖霉素
• 中文别名: 大观霉素
• 英文名称: ribostamycin
• 英文别名: (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol
• CAS: 25546-65-0
• 化学式: C₁₇H₃₄N₄O₁₀
• 分子量: 454.478
• InChiKey: NSKGQURZWSPSBC-VVPCINPTSA-N

物化性质

• 熔点：
  192-195°; mp 175-180° (dec)
• 比旋光度：
  D23 +42°
• 沸点：
  561.28°C (rough estimate)
• 密度：
  1.1751 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  262
• 氢给体数：
  10
• 氢受体数：
  14

安全信息

• 危险品标志：
  T
• 安全说明：
  S22,S36/37/39,S45,S53
• 危险类别码：
  R61,R20/21/22
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  核糖霉素 在 三乙胺 作用下， 生成
  参考文献：
  名称：

  氨基糖苷微阵列研究抗生素耐药性。

  摘要：

  DOI：

  10.1002/anie.200353236
• 作为产物：
  描述：

  在 吡啶 、 jones reagent 、 camphor-10-sulfonic acid 、 三氟化硼乙醚 、 sodium methylate 、 对甲苯磺酸 、 一水合肼 作用下， 以 吡啶 、 甲醇 、 硝基甲烷 、 苯 为溶剂， 反应 94.67h， 生成 核糖霉素
  参考文献：
  名称：

  核糖霉素的合成。从碳水化合物到氨基环醇的化学转化方法的应用

  摘要：

  氨基糖苷类抗生素核糖霉素是由 D-葡糖胺和核糖通过氨基-三糖中间体合成的，该中间体是通过对 1,6-脱水-D-葡糖胺部分的连续选择性糖苷化制备的。

  DOI：

  10.1246/cl.1984.2097

文献信息

• Inhibitors of aminoglycoside 6'-N-acetyltransferases, compositions and uses thereof
  申请人：Auclair Karine

  公开号：US20060211634A1

  公开（公告）日：2006-09-21

  The present invention relates to inhibitors of aminoglycoside 6′-N-acetyltransferases of Formula I: R—X—Y-Z  Formula I wherein: R is selected from the group consisting of: R 1 is selected from the group consisting of OH and R 2 is selected from the group consisting of OH and R 3 is selected from the group consisting of NH 2 and OH; R 4 is selected from the group consisting of NH 2 and R 5 is selected from the group consisting of OMe, OEt OPr, and O-iPr; X is selected from the group consisting of NH and O; Y is selected from the group consisting of: R 6 is selected from the group consisting of OH, CH 3 , and OCH 3 ; n is an integer ranging from 1 to 10; and Z is selected from the group consisting of: and R 7 is selected from the group consisting of OH, OMe, OEt OPr, O-iPr, O-tBu and

  本发明涉及公式I的氨基糖苷6'-N-乙酰转移酶抑制剂：R—X—Y-Z 其中：R选自以下组成的群体：R1选自OH和R2选自OH和R3选自NH2和OH；R4选自NH2和R5选自OMe、OEt、OPr和O-iPr；X选自NH和O；Y选自以下组成的群体：R6选自OH、CH3和OCH3；n为1至10的整数；Z选自以下组成的群体：和R7选自OH、OMe、OEt、OPr、O-iPr、O-tBu。
• The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase
  作者：Qingzhi Fan、Fanglu Huang、Peter F. Leadlay、Jonathan B. Spencer

  DOI：10.1039/b808734b

  日期：——

  An efficient protocol has been developed for the genetic manipulation of Streptomyces fradiae NCIMB 8233, which produces the 2-deoxystreptamine (2-DOS)-containing aminoglycoside antibiotic neomycin. This has allowed the in vivo analysis of the respective roles of the glycosyltransferases Neo8 and Neo15, and of the deacetylase Neo16 in neomycin biosynthesis. Specific deletion of each of the neo8, neo15 and neo16 genes confirmed that they are all essential for neomycin biosynthesis. The pattern of metabolites produced by feeding putative pathway intermediates to these mutants provided unambiguous support for a scheme in which Neo8 and Neo15, whose three-dimensional structures are predicted to be highly similar, have distinct roles: Neo8 catalyses transfer of N-acetylglucosamine to 2-DOS early in the pathway, while Neo15 catalyses transfer of the same aminosugar to ribostamycin later in the pathway. The in vitro substrate specificity of Neo15, purified from recombinant Escherichia coli, was fully consistent with these findings. The in vitro activity of Neo16, the only deacetylase so far recognised in the neo gene cluster, showed that it is capable of acting in tandem with both Neo8 and Neo15 as previously proposed. However, the deacetylation of N-acetylglucosaminylribostamycin was still observed in a strain deleted of the neo16 gene and fed with suitable pathway precursors, providing evidence for the existence of a second enzyme in S. fradiae with this activity.

  针对产生含2-脱氧链霉胺（2-DOS）的氨基糖苷类抗生素新霉素的Streptomyces fradiae NCIMB 8233，已开发出一种高效的基因操作协议。这一协议使得能够在活体内分析糖基转移酶Neo8和Neo15以及脱乙酰酶Neo16在新霉素生物合成中所发挥的各自作用。对neo8、neo15和neo16基因的特异性删除确认了它们对于新霉素的生物合成都是必不可少的。向这些突变体中添加假定途径中间体所产生的代谢物模式明确支持了以下方案：Neo8和Neo15的三维结构预测高度相似，但它们的角色截然不同：Neo8在途径的早期催化N-乙酰葡萄糖胺向2-DOS的转移，而Neo15则在途径的后期催化同一氨基糖向瑞斯托霉素的转移。从重组的大肠杆菌中纯化得到的Neo15的体外底物特异性完全符合这些发现。作为目前唯一被认识到的neo基因簇中的脱乙酰酶，Neo16的体外活性显示它能够像先前所提议的那样与Neo8和Neo15进行串联作用。然而，在删除了neo16基因且喂食了适宜途径前体的菌株中，仍然观察到了N-乙酰葡萄糖胺瑞斯托霉素的脱乙酰作用，这为S. fradiae中存在第二种具有此活性的酶提供了证据。
• Combined Chemical-Enzymatic Assembly of Aminoglycoside Derivatives with N-1-AHB Side Chain
  作者：Igor Nudelman、Lilach Chen、Nicholas M. Llewellyn、El-Habib Sahraoui、Marina Cherniavsky、Jonathan B. Spencer、Timor Baasov

  DOI：10.1002/adsc.200800229

  日期：2008.8.4

  A series of unprotected pseudo-disaccharides and pseudo-trisaccharides of 2-deoxystreptamine-containing aminoglycosides have been selectively acylated at the N-1 position with the valuable (S)-4-amino-2-hydroxybutanoyl (AHB) pharmacophore by using the recombinant BtrH and BtrG enzymes from butirosin biosynthesis in combination with a synthetic acyl donor. The process was optimized by performing two

  通过使用重组体，在有价值的（S）-4-氨基-2-羟基丁酰基（AHB）药效基团的N-1位选择性地酰化了一系列含2-脱氧链胺胺的氨基糖苷的一系列未保护的伪二糖和伪三糖。Butirosin生物合成中的BtrH和BtrG酶与合成的酰基供体结合。通过在不纯化中间产物的情况下依次进行两个酶促步骤来优化工艺。
• [EN] REGIOSELECTIVE DIAZOTATION OF AMINOGLYCOSIDES<br/>[FR] DIAZOTATION RÉGIOSÉLECTIVE DES AMINOGLYCOSIDES
  申请人：UNIV GRONINGEN

  公开号：WO2013191550A1

  公开（公告）日：2013-12-27

  The invention relates to the field of chemical derivatization. In particular, it relates to modified aminoglycosides, such as antibiotics, and methods for producing them. Provided is a method for the regioselective diazotation of a desoxy-streptamine- substituted aminoglycoside, comprising contacting the aminoglycoside with imidazole- -sulfonyl azide hydrochloride under neutral p H conditions to allow for the conversion of the single amine group at the 3-C position of the desoxy-streptamine ring into an azide group. Also provided are novel antibiotic compounds.

  该发明涉及化学衍生化领域。具体而言，涉及改性氨基糖苷，如抗生素，以及生产它们的方法。提供了一种用于对去氧链霉素取代氨基糖苷进行区域选择性重氮化的方法，包括将氨基糖苷与咪唑-磺酰叠氮氯化物在中性 pH 条件下接触，以便将去氧链霉素环的3-C 位置的单胺基转化为叠氮基团。还提供了新型抗生素化合物。
• Major increases of the reactivity and selectivity in aminoglycoside O-alkylation due to the presence of fluoride ions
  作者：Olivier Jackowski、Antoine Bussière、Cécile Vanhaverbeke、Isabelle Baussanne、Eric Peyrin、Marie-Paule Mingeot-Leclercq、Jean-Luc Décout

  DOI：10.1016/j.tet.2011.10.102

  日期：2012.1

  were observed in the presence of tetrabutylammonium fluoride (TBAF) in comparison to TBAI under phase-transfer conditions or in solution. The presence of TBAF allowed the selective and rapid alkylation of the 6-hydroxyl function of neamine and efficient preparation of protected intermediates useful in synthesis and potent or potential antimicrobial O-alkylated derivatives of neamine and paromamine. In

  在相转移条件下或在溶液中，与TBAI相比，在四丁基氟化铵（TBAF）的存在下，观察到氨基糖和糖O-烷基化反应中选择性和/或反应性的显着增加。TBAF的存在可以使神经胺的6-羟基官能团选择性地和快速地烷基化，并且可以有效地制备用于合成的保护的中间体以及对神经胺和巴胺的有效或潜在的抗菌的O-烷基化衍生物。关于所观察到的TBAF的强作用，值得在相转移条件下在TBAF存在下研究碳水化合物的烷基化和酰化。