teicoplanin A2-2 | 91032-35-8

• 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: teicoplanin A2-2
• 英文别名: (1S,2R,19R,22R,34S,37R,40R,52S)-2-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-azaniumyl-5,15-dichloro-64-[(2S,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(8-methylnonanoylamino)oxan-2-yl]oxy-26,31,44,49-tetrahydroxy-21,35,38,54,56,59-hexaoxo-47-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-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-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49,62,65-henicosaene-52-carboxylate
• CAS: 91032-35-8
• 化学式: C₈₈H₉₇Cl₂N₉O₃₃
• 分子量: 1879.68
• InChiKey: GHOXVFYORXUCPY-PKMGYIMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  132
• 可旋转键数：
  19
• 环数：
  16.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  662
• 氢给体数：
  24
• 氢受体数：
  34

反应信息

• 作为反应物：
  描述：

  teicoplanin A2-2 在 C₂₀H₃₆N₄O₇ 、 N-溴酞亚胺 作用下， 以 甲醇 、 水 为溶剂， 反应 1.08h， 以19%的产率得到(1S,2R,19R,22R,34S,37R,40R,52S)-2-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-amino-50-bromo-5,15-dichloro-64-[(2S,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(8-methylnonanoylamino)oxan-2-yl]oxy-26,31,44,49-tetrahydroxy-21,35,38,54,56,59-hexaoxo-47-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-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-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46,48,50,62,65-henicosaene-52-carboxylic acid
  参考文献：
  名称：

  用位点选择性反应化学定制替考拉宁

  摘要：

  天然产物衍生物的半合成将发酵的力量与正交化学反应相结合。然而，复杂结构的化学修饰是一个尚未解决的挑战，因为选择性差通常会降低效率。复合抗生素替考拉宁可根除细菌感染。然而，随着耐药性的出现，对改良类似物的需求也在增长。我们发现了实现替考拉宁位点选择性改变的化学反应。利用改变反应选择性的基于肽的添加剂，可以使用某些溴代替考拉宁。这些新化合物也是选择性交叉偶联反应的支架，可进一步实现分子多样化。这些研究能够两步获得糖肽类似物，这些糖肽类似物不能单独通过生物合成或快速全化学合成获得。

  DOI：

  10.1021/ja4038998

文献信息

• Amides of de-acetylglucosaminyl-deoxy teicoplanin active against highly glycopeptide-resistant enterococci. Synthesis and antibacterial activity.
  作者：ADRIANO MALABARBA、ROMEO CIABATTI、JÜRGEN KETTENRING、PIETRO FERRARI、ROBERTO SCOTTI、BETH P. GOLDSTEIN、MAURIZIO DENARO

  DOI：10.7164/antibiotics.47.1493

  日期：——

  Removal, by selective reduction, of the acetylglucosamine from teicoplanin A2-2 (CTA/2) produced the 34-de(acetylglucosaminyl)-34-deoxy pseudoaglycone (II). This compound was more active in vitro than CTA/2 against coagulase-negative staphylococci (CNS). Amide derivatives obtained by condensation of the carboxyl group of II with primary amines were particularly active against Streptococcus pyogenes

  通过选择性还原从替考拉宁A2-2（CTA / 2）中除去乙酰氨基葡糖，产生了34-脱（乙酰氨基葡萄糖基）-34-脱氧假糖苷配基（II）。与CTA / 2相比，该化合物对凝血酶阴性葡萄球菌（CNS）的体外活性更高。通过II的羧基与伯胺的缩合获得的酰胺衍生物对化脓性链球菌特别有活性，并且对高耐替考拉宁和万古霉素的VanA肠球菌具有一定的体外活性。其中，具有支链四胺的羧酰胺（VII）也比相应的替考拉宁酰胺对CNS具有更好的活性。相反，II的二甲基酰胺（VIII）对VanA肠球菌几乎没有活性。II的二级羧酰胺的七肽骨架的总体结构与CTA / 2及其酰胺衍生物中的相同，而在脱氧假糖苷配基II和其叔酰胺VIII中，51,52-肽键与原始结构发生构象变化顺式至顺式取向。II和二甲酰胺VIII的仲酰胺之间的这种差异反映在它们不同的抗菌谱上。还描述了通过与硼氢化钠反应从母体CTA / 2-酰胺直接合成脱氧假
• Role of the Carbohydrate Moieties in Chiral Recognition on Teicoplanin-Based LC Stationary Phases
  作者：Alain Berthod、Xianghong Chen、John P. Kullman、Daniel W. Armstrong、Francesco Gasparrini、Ilaria D'Acquaric、Claudio Villani、Angelo Carotti

  DOI：10.1021/ac991004t

  日期：2000.4.1

  of an aglycone peptide "basket" with three attached carbohydrate (sugar) moieties. The sugar units were removed and the aglycone was purified. Two chiral stationary phases (CSPs) were prepared in a similar way, one with the native teicoplanin molecule and the other with the aglycone. Twenty-six compounds were evaluated on the two CSPs with seven RPLC mobile phases and two polar organic mobile phases

  在这项研究中，我们使用了大环抗生素替考拉宁，该分子由糖苷配基肽“篮子”和三个附着的碳水化合物（糖）部分组成。除去糖单元并纯化糖苷配基。以相似的方式制备了两个手性固定相（CSP），一个带有天然替考拉宁分子，另一个带有糖苷配基。在具有七个RPLC流动相和两个极性有机流动相的两个CSP上评估了26种化合物。这些化合物是13种氨基酸或与结构相关的化合物（包括DOPA，亚叶酸等）和其他13种化合物（例如肉碱，溴苯甲酰胺等）。色谱结果以保留，选择性，和分离因子，以及对应于两种对映异构体分离的峰效率和对映选择性自由能差。两个CSP的极性相似。已经清楚地确定，糖苷配基负责氨基酸的对映体分离。对于氨基酸对映体分离，糖苷配基CSP和替考拉宁CSP之间的对映选择性自由能之差在0.3和1 kcal / mol之间。与糖苷配基CSP相比，分离度提高了2-5倍。仅在替考拉宁CSP上分离了四种非氨基酸化合物。在替考拉宁
• Multiple Complexes of Long Aliphatic <i>N</i>-Acyltransferases Lead to Synthesis of 2,6-Diacylated/2-Acyl-Substituted Glycopeptide Antibiotics, Effectively Killing Vancomycin-Resistant Enterococcus
  作者：Syue-Yi Lyu、Yu-Chen Liu、Chin-Yuan Chang、Chuen-Jiuan Huang、Ya-Huang Chiu、Chun-Man Huang、Ning-Shian Hsu、Kuan-Hung Lin、Chang-Jer Wu、Ming-Daw Tsai、Tsung-Lin Li

  DOI：10.1021/ja504125v

  日期：2014.8.6

  Teicoplanin A2-2 (Tei)/A40926 is the last-line antibiotic to treat multidrug-resistant Gram-positive bacterial infections, e.g., methicillinresistant Staphylococcus aurcus (MRSA) and vancomycin-resistant enterococcus (VRE). This class of antibiotics is powered by the N-acyltransferase (NAT) Orf11*/Dbv8 through N-acylation on glucosamine at the central residue of Tei/A40926 pseudoaglycone. The NAT enzyme possesses enormous value in untapped applications; its advanced development is hampered largely due to a lack of structural information. In this report, we present eight high-resolution X-ray crystallographic unary, binary, and ternary complexes in order to decipher the molecular basis for NAT's functionality. The enzyme undergoes a multistage conformational change upon binding of acyl-CoA, thus allowing the uploading of Tei pseudoaglycone to enable the acyl-transfer reaction to take place in the occlusion between the N- and C-halves of the protein. The acyl moiety of acyl-CoA can be bulky or lengthy, allowing a large extent of diversity in new derivatives that can be formed upon its transfer. Vancomycin/synthetic acyl-N-acetyl cysteamine was not expected to be able to serve as a surrogate for an acyl acceptor/donor, respectively. Most strikingly, NAT can catalyze formation of 2-N,6-O-diacylated or C6 -> C2 acyl-substituted Tei analogues through an unusual 1,4-migration mechanism under stoichiometric/solvational reaction control, wherein selected representatives showed excellent biological activities, effectively counteracting major types (VanABC) of VRE.
• 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.
• Structural Modifications of the Active Site in Teicoplanin and Related Glycopeptides. 1. Reductive Hydrolysis of the 1,2- and 2,3-Peptide Bonds
  作者：Adriano Malabarba、Romeo Ciabatti、Jürgen Kettenring、Pietro Ferrari、Károly Vékey、Elvio Bellasio、Maurizio Denaro

  DOI：10.1021/jo941809v

  日期：1996.1.1

  Reaction of teicoplanin glycopeptides with sodium borohydride in aqueous ethanol solutions produced open pentapeptide derivatives in which the amide bond between amino acids 2 and 3 was hydrolyzed and the carboxyl group of amino acid 2 was reduced to a primary alcohol. Other glycopeptides of the dalbaheptide family, such as vancomycin, ristocetin, and A-40,926, underwent selective reductive hydrolysis (RH) of the heptapeptide backbone at the same position as in teicoplanins, while antibiotic A-42,867 and vancomycin hexapeptide were resistant. Also, teicoplanin and vancomycin were resistant to RH-treatment when the N-terminus was protected as carbamate. In contrast, open hexapeptides in which the 1,2-peptide bond was hydrolyzed and the carboxyl group of amino acid 1 was reduced to hydroxymethyl were obtained from carbamate derivatives of sugar-free compounds deglucoteicoplanin (TD) and vancomycin-aglycon (VA) under RH-conditions. Limited to BOC or CBZ-TD, the 3,4-amide bond was also affected. A possible RH-mechanism is proposed for natural glycopeptides and their derivatives. Teicoplanin-derived RH penta- and hexapeptides maintained residual antibacterial activity. As other analogous RH-glycopeptides, they are key intermediates for the synthesis of new members of this family of antibiotics. A synthetic approach to ring-closed derivatives of TD hexapeptide alcohol (TDHPA) and their activities are also reported.