ristocetin aglycone | 73201-25-9

• 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: ristocetin aglycone
• 英文别名: Aglycoristocetin；methyl (1S,2R,18R,19R,22R,34S,37R,40R,52S)-22-amino-2,18,26,31,44,47,49,64-octahydroxy-30-methyl-21,35,38,54,56,59-hexaoxo-7,13,28-trioxa-20,36,39,53,55,58-hexazaundecacyclo[38.14.2.23,6.214,17.219,34.18,12.123,27.129,33.141,45.010,37.046,51]hexahexaconta-3(66),4,6(65),8,10,12(64),14(63),15,17(62),23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49-henicosaene-52-carboxylate
• CAS: 73201-25-9
• 化学式: C₆₀H₅₁N₇O₁₉
• 分子量: 1174.1
• InChiKey: OYQWICYKFCGTRN-CAJRPZEHSA-N

物化性质

• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  86
• 可旋转键数：
  2
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  416
• 氢给体数：
  15
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  ristocetin aglycone 在 2-异丙叉-2-氧代乙醛 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以1.61 g的产率得到Ristocetin ketone
  参考文献：
  名称：

  Preparation of biologically active ristocetin derivatives: replacements of the 1'-amino group

  摘要：

  A series of ristocetin analogues with modifications (OH, C=O, C=NOH, NCOCH3) at the C-1' amino group was synthesized and found to possess antibacterial activity against gram-positive bacteria and to bind to Ac2-Lys-D-Ala-D-Ala, a model for the antibiotic's site of action. Due to the lack of a positively charged amino group, the active analogues could not form a salt bridge, indicating that an electrostatic interaction between the positively charged 1'-amino group of ristocetin and the carboxylate anion of the peptide is not required for complex formation. The only compound that did not exhibit good antibacterial activity was epiristocetin aglycone (an analogue with the 1'amino group in the opposite configuration (S) as ristocetin). On the basis of NMR studies of epiristocetin aglycone in solution, the 1'-amino group is located in the proposed carboxylate binding pocket and may sterically block complex formation.

  DOI：

  10.1021/jm00147a047
• 作为产物：
  描述：

  生成 ristocetin aglycone
  参考文献：
  名称：

  TRIFONOVA ZH. P.; KOBRIN M. B.; STURMAN N. V.; KATRUXA G. S., PERSPEKTIVY SOZDANIYA LEKARSTV. SREDSTV S ISPOLZ. BIOTEXNOL. TEZ. DOKL. B+

  摘要：

  DOI：

文献信息

• Total Synthesis of the Ristocetin Aglycon
  作者：Brendan M. Crowley、Yoshiki Mori、Casey C. McComas、Datong Tang、Dale L. Boger

  DOI：10.1021/ja039795a

  日期：2004.4.1

  The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively

  采用模块化和高度收敛的策略描述了瑞斯托菌素苷元的首次全合成。ABCD 环系统 3 从其氨基酸亚基的有效 12 步（总体 12%）合成依次具有分子内芳香亲核取代反应，用于形成二芳基醚和 16 元 CD 环系统的闭合（65%） ，分别为非对映选择性 (3:1, 86%) Suzuki 偶联，用于安装可进一步热调节阻转异构体立体化学的 AB 联芳基键，以及用于闭合 12 元 AB 环系统的有效大环内酰胺化 (51%) .
• Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
  作者：Ilona Bereczki、Henrietta Papp、Anett Kuczmog、Mónika Madai、Veronika Nagy、Attila Agócs、Gyula Batta、Márton Milánkovits、Eszter Ostorházi、Ana Mitrović、Janko Kos、Áron Zsigmond、István Hajdú、Zsolt Lőrincz、Dávid Bajusz、György Miklós Keserű、Jan Hodek、Jan Weber、Ferenc Jakab、Pál Herczegh、Anikó Borbás

  DOI：10.3390/ph14111111

  日期：——

  development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2

  旷日持久的全球 COVID-19 大流行促使开发针对病原体 SARS-CoV-2 的新药。临床上使用的糖肽类抗生素替考拉宁成为一种潜在的抗病毒药物，并且通过亲脂性修饰提高了其疗效。这促使我们制备替考拉宁、其假糖苷配基和相关瑞斯托霉素糖苷配基的新型亲脂性类胡萝卜素缀合物。使用细胞活力测定和病毒 RNA 的定量 PCR 在 Vero E6 细胞中测试了它们对 SARS-CoV-2 的抗病毒作用，证实了它们对病毒复制的微摩尔抑制活性。有趣的是，母体类胡萝卜素中的两种，bixin 和 β-apo-8'胡萝卜素酸，发挥了显着的抗 SARS-CoV-2 活性。机制研究涉及组织蛋白酶 L 和 B，以及主要蛋白酶 3CLPro，并且通过计算研究使结果合理化。糖肽缀合物显示双重抑制作用，而类胡萝卜素主要具有组织蛋白酶 B 和 L 亲和力。由于替考拉宁是一种上市抗生素，而天然碧玺是一种经批准、廉价且广泛使用的
• Synthesis and evaluation of methyl ether derivatives of the vancomycin, teicoplanin, and ristocetin aglycon methyl esters
  作者：Casey C. McComas、Brendan M. Crowley、Inkyu Hwang、Dale L. Boger

  DOI：10.1016/s0960-894x(03)00513-4

  日期：2003.9

  A series of methyl ether derivatives of the vancomycin, teicoplanin, and ristocetin aglycon methyl esters was synthesized and their antimicrobial activity was established. These derivatives exhibit increased activity against VanB resistant strains of bacteria equipotent with that observed with sensitive bacteria.

  合成了万古霉素，替考拉宁和瑞斯托汀糖苷配基甲基酯的一系列甲基醚衍生物，并确定了它们的抗菌活性。这些衍生物对与敏感细菌所观察到的细菌等效的VanB抗性菌株表现出增强的活性。
• A new and improved method for deglycosidation of glycopeptide antibiotics exemplified with vancomycin, ristocetin, and ramoplanin
  作者：Jutta Wanner、Datong Tang、Casey C McComas、Brendan M Crowley、Wanlong Jiang、Jason Moss、Dale L Boger

  DOI：10.1016/s0960-894x(03)00051-9

  日期：2003.3

  A general method for the deglycosidation of glycopeptide antibiotics has been developed. Treatment of vancomycin, ristocetin, and ramoplanin with anhydrous HF results in efficient cleavage of the sugars to provide the corresponding aglycons in high yield.

  已经开发出用于糖肽抗生素的去糖基化的通用方法。用无水HF处理万古霉素，瑞斯托菌素和雷莫拉宁可有效裂解糖，从而以高收率提供相应的糖苷配基。
• Diazo Transfer−Click Reaction Route to New, Lipophilic Teicoplanin and Ristocetin Aglycon Derivatives with High Antibacterial and Anti-influenza Virus Activity: An Aggregation and Receptor Binding Study
  作者：Gábor Pintér、Gyula Batta、Sándor Kéki、Attila Mándi、István Komáromi、Krisztina Takács-Novák、Ferenc Sztaricskai、Erzsébet Röth、Eszter Ostorházi、Ferenc Rozgonyi、Lieve Naesens、Pál Herczegh

  DOI：10.1021/jm900950d

  日期：2009.10.8

  Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components Was Studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.