(S)-(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((tert-butoxycarbonyl)amino)hexanoic (isobutyl carbonic) anhydride | 285117-08-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((tert-butoxycarbonyl)amino)hexanoic (isobutyl carbonic) anhydride
• CAS: 285117-08-0
• 化学式: C₃₁H₄₀N₂O₈
• 分子量: 568.667
• InChiKey: XQBRSQPGQKPNFU-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.92
• 重原子数：
  41.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  129.26
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (S)-(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((tert-butoxycarbonyl)amino)hexanoic (isobutyl carbonic) anhydride 在 sodium tetrahydroborate 、 sodium azide 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成
  参考文献：
  名称：

  应用小分子芯片和所得的亲和力探针鸡尾酒的哺乳动物细胞裂解液的蛋白质组分析。

  摘要：

  事实证明，小分子微阵列（SMM）越来越成为评估蛋白质与配体相互作用以及以高通量方式筛选酶底物和抑制剂的重要工具。我们之前描述了一种SMM辅助的筛选策略，用于快速鉴定针对天冬氨酸蛋白酶γ-分泌酶的探针。在本文中，我们将扩展使用羟乙基胺衍生的抑制剂的扩展库，该抑制剂非排他性地针对天冬氨酸蛋白酶。我们的库在P 2，P 1，P 1 '和P 2 '上是多样化的职位。因此，使用组合固相合成方法合成了86种新抑制剂，使总文库大小达到284种生物素化化合物，并排列在抗生物素蛋白载玻片上。为了阐明复杂生物样品中的酶活性和特性，使用荧光标记的哺乳动物细胞裂解液进行了筛选。这产生了可再现的图谱或结合指纹，与天冬氨酸蛋白酶或辅助蛋白以及样品中存在的其他相互作用靶标的相互作用相对应。最亮的芯片命中率转换为基于亲和力的探针（A fBP）使用便捷的第一步“点击”化学反应，并使用来自相关构件的二苯甲酮。使用这些探针（个人

  DOI：

  10.1002/asia.201100523
• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 氯甲酸异丁酯 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 (S)-(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((tert-butoxycarbonyl)amino)hexanoic (isobutyl carbonic) anhydride
  参考文献：
  名称：

  应用小分子芯片和所得的亲和力探针鸡尾酒的哺乳动物细胞裂解液的蛋白质组分析。

  摘要：

  事实证明，小分子微阵列（SMM）越来越成为评估蛋白质与配体相互作用以及以高通量方式筛选酶底物和抑制剂的重要工具。我们之前描述了一种SMM辅助的筛选策略，用于快速鉴定针对天冬氨酸蛋白酶γ-分泌酶的探针。在本文中，我们将扩展使用羟乙基胺衍生的抑制剂的扩展库，该抑制剂非排他性地针对天冬氨酸蛋白酶。我们的库在P 2，P 1，P 1 '和P 2 '上是多样化的职位。因此，使用组合固相合成方法合成了86种新抑制剂，使总文库大小达到284种生物素化化合物，并排列在抗生物素蛋白载玻片上。为了阐明复杂生物样品中的酶活性和特性，使用荧光标记的哺乳动物细胞裂解液进行了筛选。这产生了可再现的图谱或结合指纹，与天冬氨酸蛋白酶或辅助蛋白以及样品中存在的其他相互作用靶标的相互作用相对应。最亮的芯片命中率转换为基于亲和力的探针（A fBP）使用便捷的第一步“点击”化学反应，并使用来自相关构件的二苯甲酮。使用这些探针（个人

  DOI：

  10.1002/asia.201100523

文献信息

• General, Mild, and Metal-Free Synthesis of Phenyl Selenoesters from Anhydrides and Their Use in Peptide Synthesis
  作者：Andrea Temperini、Francesca Piazzolla、Lucio Minuti、Massimo Curini、Carlo Siciliano

  DOI：10.1021/acs.joc.7b00173

  日期：2017.5.5

  A mild, practical, and simple procedure for phenyl selenoesters synthesis from several anhydrides and diphenyl diselenide was developed. This transition-metal-free method provides a straightforward entry to storable Fmoc-amino acid selenoesters which are effective chemoselective acylating reagents. An application to oligopeptide synthesis was illustrated.

  开发了一种温和，实用和简单的方法，用于从几种酸酐和二苯基二硒化物合成苯基硒酸酯。这种无过渡金属的方法可以直接进入可存储的Fmoc-氨基酸硒酸酯，它们是有效的化学选择性酰化试剂。说明了在寡肽合成中的应用。
• Thio Acid/Azide Amidation:  An Improved Route to <i>N</i>-Acyl Sulfonamides
  作者：Kristin N. Barlett、Robert V. Kolakowski、Sreenivas Katukojvala、Lawrence J. Williams

  DOI：10.1021/ol052671d

  日期：2006.3.2

  A one-pot procedure for the conversion of carboxylic acids to N-acyl sulfonamides, via thio acid/azide amidation, is presented. The method is compatible with acid- and base-sensitive amino acid protection. N-Acyl sulfonamide synthesis on solid support, peptide thio acid/sulfonazide coupling, and N-alkyl amide synthesis via selective cleavage of sulfonyl from an N-alkyl-N-acyl sulfonamide are also reported

  提出了一种一锅法，用于通过硫代酸/叠氮化物酰胺化将羧酸转化为N-酰基磺酰胺。该方法与对酸和碱敏感的氨基酸保护兼容。还报道了在固体载体上合成N-酰基磺酰胺，肽硫酸/磺叠氮化物偶联以及通过从N-烷基-N-酰基磺酰胺选择性裂解磺酰基而合成的N-烷基酰胺。
• Rationale-Based, <i>De Novo</i> Design of Dehydrophenylalanine-Containing Antibiotic Peptides and Systematic Modification in Sequence for Enhanced Potency
  作者：Sarika Pathak、Virander Singh Chauhan

  DOI：10.1128/aac.01493-10

  日期：2011.5

  Increased microbial drug resistance has generated a global requirement for new anti-infective agents. As part of an effort to develop new, low-molecular-mass peptide antibiotics, we used a rationale-based minimalist approach to design short, nonhemolytic, potent, and broad-spectrum antibiotic peptides with increased serum stability. These peptides were designed to attain an amphipathic structure in helical conformations. VS1 was used as the lead compound, and its properties were compared with three series of derivates obtained by (i) N-terminal amino acid addition, (ii) systematic Trp substitution, and (iii) peptide dendrimerization. The Trp substitution approach underlined the optimized sequence of VS2 in terms of potency, faster membrane permeation, and cost-effectiveness. VS2 (a variant of VS1 with two Trp substitutions) was found to exhibit good antimicrobial activity against both the Gram-negative Escherichia coli and the Gram-positive bacterium Staphylococcus aureus . It was also found to have noncytolytic activity and the ability to permeate and depolarize the bacterial membrane. Lysis of the bacterial cell wall and inner membrane by the peptide was confirmed by transmission electron microscopy. A combination of small size, the presence of unnatural amino acids, high antimicrobial activity, insignificant hemolysis, and proteolytic resistance provides fundamental information for the de novo design of an antimicrobial peptide useful for the management of infectious disease.

  摘要 微生物耐药性的增加催生了全球对新型抗感染药物的需求。作为开发新型低分子质量多肽抗生素努力的一部分，我们采用基于理性的极简方法设计出了短小、不溶血、强效、广谱且血清稳定性更高的抗生素多肽。这些多肽被设计成螺旋构象的两性结构。以 VS1 为先导化合物，将其特性与通过以下方法获得的三个系列衍生物进行了比较：(i) N 端氨基酸添加；(ii) 系统性 Trp 取代；(iii) 肽树枝化。Trp 取代方法强调了 VS2 在效力、更快的膜渗透性和成本效益方面的优化序列。研究发现，VS2（VS1 的变体，有两个 Trp 取代）对革兰氏阴性的 大肠杆菌 和革兰氏阳性细菌 金黄色葡萄球菌 .研究还发现它具有非细胞溶解活性以及渗透和去极化细菌膜的能力。透射电子显微镜证实了该肽对细菌细胞壁和内膜的裂解作用。小尺寸、非天然氨基酸的存在、高抗菌活性、微量溶血和抗蛋白水解等特性为 从头 为从头设计一种可用于治疗传染病的抗菌肽提供了基本信息。
• Preparation of Potassium Acyltrifluoroborates (KATs) from Carboxylic Acids by Copper‐Catalyzed Borylation of Mixed Anhydrides**
  作者：Pinku Tung、Anne Schuhmacher、Philipp E. Schilling、Jeffrey W. Bode、Neal P. Mankad

  DOI：10.1002/anie.202114513

  日期：2022.2.7

  Aliphatic and aromatic carboxylic acids are rapidly converted into potassium acyltrifluoroborates (KATs) by copper-catalyzed borylation of their mixed anhydrides. This scalable method is compatible with a broad range of functional groups and allows for the facile preparation of aliphatic and aromatic KATs, including KATs derived from Fmoc- and Boc-protected amino acids.

  脂肪族和芳香族羧酸通过其混合酸酐的铜催化硼化反应迅速转化为酰基三氟硼酸钾 (KAT)。这种可扩展的方法与广泛的官能团兼容，并允许轻松制备脂肪族和芳香族 KAT，包括衍生自 Fmoc 和 Boc 保护的氨基酸的 KAT。
• A Peptide Aldehyde Microarray for High-Throughput Profiling of Cellular Events
  作者：Hao Wu、Jingyan Ge、Peng-Yu Yang、Jigang Wang、Mahesh Uttamchandani、Shao Q. Yao

  DOI：10.1021/ja109597v

  日期：2011.2.16

  Microarrays provide exciting opportunities in the field of large-scale proteomics. With the aim to elucidate enzymatic activity and profiles within native biological samples, we developed a microarray comprising a focused positional-scanning library of enzyme inhibitors. The library was diversified across P-1-P-4 positions, creating 270 different inhibitor sublibraries which were immobilized onto avidin slides. The peptide aldehyde-based small-molecule microarray (SMM) specifically targeted cysteine proteases, thereby enabling large-scale functional assessment of this subgroup of proteases, within fluorescently labeled samples, including pure proteins, cellular lysates, and infected samples. The arrays were shown to elicit binding fingerprints consistent with those of model proteins, specifically caspases and purified cysteine proteases from parasites (rhodesein and cruzain). When tested against lysates from apoptotic Hela and red blood cells infected with Plasmodium falciparum, clear signatures were obtained that were readily attributable to the activity of constituent proteases within these samples. Characteristic binding profiles were further able to distinguish various stages of the parasite infection in erythrocyte lysates. By converting one of our brightest microarray hits into a probe, putative protein markers were identified and pulled down from within apoptotic Hela lysates, demonstrating the potential of target validation and discovery. Taken together, these results demonstrate the utility of targeted SMMs in dissecting cellular biology in complex proteomic samples.