H-L-Lol-2-chlorotrityl resin

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: H-L-Lol-2-chlorotrityl resin
• 英文别名: 3-[[2-[[Bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-(6-bromohexoxy)-2-methylpropoxy]-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• 化学式: C₂₅H₂₇ClNOPol
• 分子量: 785.8
• InChiKey: RBPNBHMCTYCHBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  51
• 可旋转键数：
  25
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  82.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  H-L-Lol-2-chlorotrityl resin 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以41.9 mg的产率得到peptaibolin
  参考文献：
  名称：

  An Automatic Solid-Phase Synthesis of Peptaibols

  摘要：

  An automated approach to peptaibols using microwave-assisted solid-phase peptide synthesis is demonstrated with a combination of HBTU and acid fluoride mediated couplings for normal and alpha,alpha-dialkylated amino acids, respectively. The method is utilized for the automated synthesis of several full-length peptaibols, including alamethicin, tylopeptin, ampullosporin, bergofungin, cervinin, trikoningin, trichogin, and peptaibolin, reducing both synthesis time and costs significantly as compared to other approaches. Furthermore, the use of noncommercially available reagents is minimized.

  DOI：

  10.1021/jo802058x
• 作为产物：
  描述：

  双(二异丙基氨基)(2-氰基乙氧基)膦 、 1-O-(4,4'-dimethoxytrityl)-2-(6-bromohexyloxymethyl)-2-methyl-1,3-propanediol 在 二异丙基铵盐四氮唑 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以73%的产率得到H-L-Lol-2-chlorotrityl resin
  参考文献：
  名称：

  Synthesis of Mannose and Galactose Oligonucleotide Conjugates by Bi-click chemistry

  摘要：

  Glyco oligonucleotide conjugates, each exhibiting two mannose and two galactose residues, were efficiently synthesized by two successive 1,3-dipolar cycloadditions (click chemistry). Two phosphoramidite derivatives were used: one bearing a bromoalkyl group as a precursor to azide functionalization and another bearing a propargyl group. After a first cycloaddition with a mannosyl-azide derivative, the bromine atoms were substituted with NaN3 and a second click reaction was performed with a 1'-O-propargyl galactose, affording the heteroglyco oligonucleotide conjugate.

  DOI：

  10.1021/jo802536q

文献信息

• Synthesis, Preferred Conformation, and Membrane Activity of Medium-Length Peptaibiotics: Tylopeptin B
  作者：Marina Gobbo、Claudia Poloni、Marta De Zotti、Cristina Peggion、Barbara Biondi、Gema Ballano、Fernando Formaggio、Claudio Toniolo

  DOI：10.1111/j.1747-0285.2009.00920.x

  日期：2010.2

  The solid‐phase synthesis and full chemical characterization of the medium‐length (14‐amino acid residues) peptaibol with antibiotic properties of tylopeptin B, originally extracted from the fruiting body of the mushroom Tylopilus neofelleus, are described. These data are accompanied by the results on the solution‐phase synthesis via the segment condensation approach of a selected, side‐chain protected

  描述了最初从蘑菇Tylopilus neofelleus的子实体中提取的具有酪胺肽B的抗生素特性的中等长度（14个氨基酸残基）肽醇的固相合成和完整化学特征。这些数据都伴随着在溶液相合成的结果通过一个选择的，侧链保护的，模拟的段缩合方法。通过结合使用FTIR吸收，圆二色性和2D-NMR（后一种技术与分子动力学计算相结合）进行的溶液构象分析，得出的结论是，酪蛋白B的3D结构在很大程度上是螺旋形的，并且优先考虑α-或3 10螺旋类型取决于溶剂的性质。螺旋拓扑和（部分）两亲性特征是这种肽生物素所观察到的膜修饰特性的原因。
• Trichogin GA IV: A versatile template for the synthesis of novel peptaibiotics
  作者：Marta De Zotti、Barbara Biondi、Cristina Peggion、Fernando Formaggio、Yoonkyung Park、Kyung-Soo Hahm、Claudio Toniolo

  DOI：10.1039/c1ob06178j

  日期：——

  Trichogin GA IV, isolated from the fungus Trichoderma longibrachiatum, is the prototype of lipopeptaibols, the sub-class of short-length peptaibiotics exhibiting membrane-modifying properties. This peptaibol is predominantly folded in a mixed 310-/α- helical conformation with a clear, albeit modest, amphiphilic character, which is likely to be responsible for its capability to perturb bacterial membranes and to induce cell death. In previous papers, we reported on the interesting biological properties of trichogin GA IV, namely its good activity against Gram positive bacteria, in particular methicillin-resistant S. aureus strains, its stability towards proteolytic degradation, and its low hemolytic activity. Aiming at broadening the antimicrobial activity spectrum by increasing the peptide helical amphiphilicity, in this work we synthesized, by solution and solid-phase methodologies, purified and fully characterized a set of trichogin GA IV analogs in which the four Gly residues at positions 2, 5, 6, 9, lying in the poorly hydrophilic face of the helical structure, are substituted by one (position 2, 5, 6 or 9), two (positions 5 and 6), three (positions 2, 5, and 9), and four (positions 2, 5, 6, and 9) Lys residues. The conformational preferences of the Lys-containing analogs were assessed by FT-IR absorption, CD and 2D-NMR techniques in aqueous, organic, and membrane-mimetic environments. Interestingly, it turns out that the presence of charged residues induces a transition of the helical conformation adopted by the peptaibols (from 310- to α-helix) as a function of pH in a reversible process. The role played in the analogs by the markedly increased amphiphilicity was further tested by fluorescence leakage experiments in model membranes, protease resistance, antibacterial and antifungal activities, cytotoxicity, and hemolysis. Taken together, our biological results provide evidence that some of the least substituted among these analogs are good candidates for the development of new membrane-active antimicrobial agents.

  从真菌长链毛霉中分离出来的 Trichogin GA IV 是具有膜修饰特性的短链肽亚类--脂链肽的原型。这种蛋白胨主要折叠成 310-/α- 混合螺旋构象，具有明显的两亲性，尽管这种两亲性并不强，但这很可能是它能够扰乱细菌膜并诱导细胞死亡的原因。在以前的论文中，我们曾报道过 trichogin GA IV 有趣的生物特性，即它对革兰氏阳性细菌（尤其是耐甲氧西林金黄色葡萄球菌菌株）的良好活性、对蛋白水解降解的稳定性以及较低的溶血活性。为了通过增加肽的螺旋两亲性来拓宽其抗菌活性谱，我们在这项工作中采用溶液法和固相法合成、纯化并充分表征了一组三叶草苷 GA IV 类似物、5、6、9 位的四个 Gly 残基被一个（2、5、6 或 9 位）、两个（5 和 6 位）、三个（2、5 和 9 位）和四个（2、5、6 和 9 位）Lys 残基取代。在水性、有机和膜模拟环境中，通过傅立叶变换红外吸收、CD 和二维核磁共振技术评估了含 Lys 类似物的构象偏好。有趣的是，事实证明，带电残基的存在会诱导七叶皂苷的螺旋构象（从 310 螺旋到 α 螺旋）随 pH 值的变化而发生转变，这是一个可逆的过程。通过在模型膜中的荧光泄漏实验、蛋白酶抗性、抗菌和抗真菌活性、细胞毒性和溶血作用，进一步检验了类似物显著增加的两亲性所发挥的作用。总之，我们的生物学结果证明，这些类似物中一些取代度最低的是开发新型膜活性抗菌剂的良好候选物。
• Spectroscopically labeled peptaibiotic analogs: the 4-nitrophenylalanine infrared absorption probe inserted at different positions into trichogin GA IV
  作者：Cristina Peggion、Barbara Biondi、Marta De Zotti、Simona Oancea、Fernando Formaggio、Claudio Toniolo

  DOI：10.1002/psc.2475

  日期：2013.4

  A set of three analogs of the 10‐residue, membrane‐active lipopeptaibiotic trichogin GA IV, labeled with the promising 4‐nitrophenylalanine IR absorption probe for local polarity, was synthesized by the solid‐phase methodology, chromatographically purified, and extensively characterized. A single residue modification was inserted near the N‐terminus, in the central region, or at the C‐terminus. A solution

  通过固相方法合成了一组10个残基，具有膜活性的脂肽抗生素Trichogin GA IV的三个类似物，并用有希望的4-硝基苯丙氨酸IR吸收探针标记了局部极性，并进行了色谱纯化和广泛表征。将单个残基修饰插入N末端附近，中部区域或C末端。通过FT-IR吸收，CD和2D-NMR结合分子动力学计算进行的溶液构象分析表明，单标记类似物保持了母体化合物的整体螺旋性质。膜通透性测量和抗菌测试表明，它们具有膜修饰特性，并且在体外类似于天然脂肽抗生素的抗菌活性。我们在各种环境中的IR吸收和衰减的全反射率研究（出于溶解性原因而将水排除在外）表明1350 cm -1的4-硝基苄基带是相当有限的报告分子。版权所有©2012欧洲肽协会和John Wiley＆Sons，Ltd.
• Synthesis of Mannose and Galactose Oligonucleotide Conjugates by Bi-click chemistry
  作者：Gwladys Pourceau、Albert Meyer、Jean-Jacques Vasseur、François Morvan

  DOI：10.1021/jo802536q

  日期：2009.2.6

  Glyco oligonucleotide conjugates, each exhibiting two mannose and two galactose residues, were efficiently synthesized by two successive 1,3-dipolar cycloadditions (click chemistry). Two phosphoramidite derivatives were used: one bearing a bromoalkyl group as a precursor to azide functionalization and another bearing a propargyl group. After a first cycloaddition with a mannosyl-azide derivative, the bromine atoms were substituted with NaN3 and a second click reaction was performed with a 1'-O-propargyl galactose, affording the heteroglyco oligonucleotide conjugate.
• An Automatic Solid-Phase Synthesis of Peptaibols
  作者：Claudia U. Hjørringgaard、Jan M. Pedersen、Thomas Vosegaard、Niels Chr. Nielsen、Troels Skrydstrup

  DOI：10.1021/jo802058x

  日期：2009.2.6

  An automated approach to peptaibols using microwave-assisted solid-phase peptide synthesis is demonstrated with a combination of HBTU and acid fluoride mediated couplings for normal and alpha,alpha-dialkylated amino acids, respectively. The method is utilized for the automated synthesis of several full-length peptaibols, including alamethicin, tylopeptin, ampullosporin, bergofungin, cervinin, trikoningin, trichogin, and peptaibolin, reducing both synthesis time and costs significantly as compared to other approaches. Furthermore, the use of noncommercially available reagents is minimized.