2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl bromide

• 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: 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl bromide
• 英文别名: 2,3,4,6-TETRA-O-BENZOYL-beta-D-GLUCOPYRANOSYL BROMIDE；[(2R,3R,4S,5R,6S)-3,4,5-tribenzoyloxy-6-bromooxan-2-yl]methyl benzoate
• 化学式: C₃₄H₂₇BrO₉
• 分子量: 659.487
• InChiKey: WISFGQOOKBVKPD-CMPUJJQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl bromide 在 silver orthophosphate 、 3 A molecular sieve 、 lithium hydride 作用下， 以 硝基甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 6-[O⁶-(4-bromothenyl)-guan-9-yl]-hexyl-β-D-tetra-O-benzoylglucoside
  参考文献：
  名称：

  Monosaccharide-Linked Inhibitors of O⁶-Methylguanine-DNA Methyltransferase (MGMT):  Synthesis, Molecular Modeling, and Structure−Activity Relationships

  摘要：

  A series of potential inhibitors of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) were synthesized, characterized in detail by NMR, and tested for their ability to deplete MGMT activity in vitro. The new compounds, omega-[O-6-R-guan-9-yl]-(CH2)(n)-beta -d-glucosides with R = benzyl or 4-bromothenyl and omega = n = 2, 4, ... 12, were compared with the established inhibitors O-6 -benzylguanine (O-6-BG), 8-aza-O-6-benzylguanine (8-aza-BG), and O-6-(4-bromothenyl)guanine (4-BTG), which exhibit in an in vitro assay IC50 values of 0.62, 0.038, and 0.009 muM, respectively. Potential advantages of the glucosides are improved water solubility and selective uptake in tumor cells. The 4-BTG glucosides with n = 2, 4, 6 show moderate inhibition with an IC50 of ca. 0.5 muM, while glucosides derived from BG and 8-aza-BG showed significantly poorer inhibition compared to the parent compounds. The 4-BTG glucosides with n = 8, 10, 12 were effective inhibitors with IC50 values of ca. 0.03 muM. To understand this behavior, extensive molecular modeling studies were performed using the published crystal structure of MGMT (PDB entry: 1QNT). The inhibitor molecules were docked into the BG binding pocket, and molecular dynamics simulations with explicit water molecules were carried out. Stabilization energies for the interactions of specific regions of the inhibitor and individual amino acid residues were calculated. The alkyl spacer is located in a cleft along helix 6 of MGMT. With increasing spacer length there is increasing interaction with several amino acid residues which play an important role in the proposed nucleotide flipping mechanism required for DNA repair.

  DOI：

  10.1021/jm010006e
• 作为产物：
  描述：

  可得然胶 在 4-二甲氨基吡啶 、 氢溴酸 、 溶剂黄146 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 生成 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl bromide
  参考文献：
  名称：

  糖修饰磺胺作为碳酸酐酶 IX 抑制剂的合成、分子对接分析和生物学评价

  摘要：

  基于“尾法”策略，设计合成了15种新型糖修饰磺胺类药物。新化合物被评估为三种人碳酸酐酶 (CA) 异构体的抑制剂，即细胞质 CA II、跨膜 CA IX 和 XII。这些化合物中的大多数显示出对 CA 的良好活性和高拓扑极性表面积 (TPSA) 值，这对跨膜异构体 CA IX 和 XII 的选择性抑制具有积极作用。在体外活性研究中，化合物16a、16b和16e在缺氧条件下降低了高表达 CA IX 的 HT-29 和 MDA-MB-231 细胞的活力。化合物16e的抑制活性对CA IX和XII高表达的人骨肉瘤细胞系MG-63的作用优于AZM。此外，高浓度的化合物16a和16b逆转了肿瘤微环境的酸化。此外，化合物16a对MDA-MB-231细胞的迁移有一定的抑制作用。以上结果表明糖类修饰的磺胺类药物对CA IX抑制剂的开发具有进一步的研究价值。

  DOI：

  10.3390/ijms222413610

文献信息

• Koenigs–Knorr Glycosylation Reaction Catalyzed by Trimethylsilyl Trifluoromethanesulfonate
  作者：Yashapal Singh、Alexei V. Demchenko

  DOI：10.1002/chem.201805527

  日期：2019.1.28

  The discovery that traditional silver(I)‐oxide‐promoted glycosidations of glycosyl bromides (Koenigs–Knorr reaction) can be greatly accelerated in the presence of catalytic trimethylsilyl trifluoromethanesulfonate (TMSOTf) is reported. The reaction conditions are very mild that allowed for maintaining a practically neutral pH and, at the same time, providing high rates and excellent glycosylation yields

  据报道，传统的氧化银（I）促进的糖基溴的糖苷化（Koenigs-Knorr 反应）在催化三氟甲磺酸三甲基硅酯（TMSOTf）的存在下可以大大加速。反应条件非常温和，可维持几乎中性的 pH 值，同时提供高速率和优异的糖基化产率。此外，还记录了一系列差异保护的糖基溴之间不寻常的反应趋势。特别是，在这些条件下，苯甲酰化的α-溴化物比其苯甲酰化的对应物更具反应性。
• Resorcinarene-Based Facial Glycosides: Implication of Detergent Flexibility on Membrane-Protein Stability
  作者：Hazrat Hussain、Yang Du、Elena Tikhonova、Jonas S. Mortensen、Orquidea Ribeiro、Claudia Santillan、Manabendra Das、Muhammad Ehsan、Claus J. Loland、Lan Guan、Brian K. Kobilka、Bernadette Byrne、Pil Seok Chae

  DOI：10.1002/chem.201605016

  日期：2017.5.17

  current study we introduce two classes of novel amphiphiles, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), where the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional

  作为膜模拟系统，去污剂胶束通常用于从脂质环境中提取膜蛋白并维持其在水性介质中的溶解度和稳定性。尽管在膜蛋白研究中具有广泛的用途，但是封装在常规去污剂中的许多膜蛋白在提取和纯化过程中往往会发生结构降解，因此有必要开发性能增强的新型试剂。在当前的研究中，我们介绍了两类新型两亲物，即基于间苯二烯的葡糖苷和麦芽糖苷两亲物（分别命名为RGA和RMA），其中烷基链从碳水化合物的头部基团中分离出来。这些面部两亲中，与金标准的常规去污剂相比，两个RGA（RGA-C11和RGA-C13）为四种被测膜蛋白赋予了显着增强的稳定性。与RMA相比，RGA相对较高的水溶性和胶束稳定性，以及此处观察到的膜蛋白稳定的总体良好行为，至少部分是由于这些糖苷的高构象柔韧性。这项研究表明去污剂的柔韧性可能是决定膜蛋白研究行为的重要因素。由于这些糖苷的高构象柔韧性。这项研究表明去污剂的柔韧性可能是决定膜蛋白研究行为的重要因素。由于
• 새로운 데옥시콜레이트 기반의 양친매성 화합물 및 이의 이용
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus 한양대학교 에리카산학협력단(120120008551) Corp. No ▼ 131471-0017977BRN ▼134-82-10205

  公开号：KR20170048646A

  公开（公告）日：2017-05-10

  본 발명은 데옥시콜레이트 기반의 양친매성 화합물, 이의 제조방법 및 이를 이용하여 막단백질을 추출, 용해화, 안정화, 결정화 또는 분석하는 방법에 관한 것이다. 본 발명에 따른 데옥시콜레이트 기반의 화합물을 이용하면 막단백질을 수용액에서 장기간 안정적으로 보관할 수 있고 작은 막단백질-미셀 복합체를 형성하여 막단백질 결정화 효과가 우수할 것으로 기대되며, 이를 통해 그 기능분석 및 구조 분석에 활용될 수 있다. 막단백질 구조 및 기능 분석은 현 생물학 및 화학에서 가장 관심을 갖고 있는 분야 중 하나이고, 현재 개발되고 있는 신약의 절반 이상이 막단백질을 타겟으로 하므로 신약 개발과 긴밀한 관계가 있는 막단백질 구조 연구에 응용이 가능하다.

  本发明涉及一种基于癸二酸酯的阳离子两性化合物、其制备方法以及利用该化合物提取、溶解、稳定、结晶或分析膜蛋白的方法。根据本发明的基于癸二酸酯的化合物可用于在溶液中长期稳定地保存膜蛋白，并形成小的膜蛋白-微粒复合体，有望获得优异的膜蛋白结晶效果，从而可用于功能分析和结构分析。膜蛋白结构和功能分析是当前生物学和化学领域最感兴趣的领域之一，目前开发的新药中有一半以上以膜蛋白为目标，因此可应用于与新药开发密切相关的膜蛋白结构研究。
• A New Method for the Synthesis of Stannyl Ethers by Acid-Catalyzed Reaction of Alcohols with Allyltributylstannane
  作者：Shigeru Yamago、Takeshi Yamada、Ryuji Nishimura、Hiroki Ito、Yosuke Mino、Jun-ichi Yoshida

  DOI：10.1246/cl.2002.152

  日期：2002.2

  Stannyl ethers are prepared by triflic acid-catalyzed reaction of alcohols with tributylstannane or allyltributylstannane at room temperature. The stannyl ethers thus prepared can be successfully used for the β-bromogycoside-mediated glycosylation reactions.

  甲锡基醚是通过三氟甲磺酸催化的醇与三丁基锡烷或烯丙基三丁基锡烷在室温下反应制备的。由此制备的甲锡醚可以成功地用于β-溴糖苷介导的糖基化反应。
• Combinatorial Synthesis of an Oligosaccharide Library by Using β-Bromoglycoside-Mediated Iterative Glycosylation of Selenoglycosides: Rapid Expansion of Molecular Diversity with Simple Building Blocks
  作者：Shigeru Yamago、Takeshi Yamada、Hiroki Ito、Osamu Hara、Yosuke Mino、Jun-ichi Yoshida

  DOI：10.1002/chem.200500126

  日期：2005.10.21

  new method for constructing an oligosaccharide library composed of structurally defined oligosaccharides is presented based on an iterative glycosylation of selenoglycosides. Treatment of 2-acyl-protected selenoglycosides with bromine selectively generates beta-bromoglycosides, which serve as glycosyl cation equivalents in the oligosaccharide synthesis. Thus, the coupling of the bromoglycosides with

  基于硒代糖苷的迭代糖基化，提出了一种构建由结构定义的寡糖组成的寡糖文库的新方法。用溴处理2-酰基保护的硒代糖苷可选择性生成β-溴代糖苷，其在寡糖合成中充当糖基阳离子等同物。因此，溴糖苷与另一硒代糖苷的偶联提供了相应的糖基化硒代糖苷，其可以直接用于下一个糖基化。该序列的迭代允许合成多种寡糖，包括激发子活性七糖。迭代糖基化的特征是，在与糖基受体偶联之前，可以通过活化糖基供体选择性地偶联糖基供体和具有相同端基反应性的受体。因此，相同的硒代糖苷可用于糖基供体和受体。通过针对激发子活性寡糖的寡糖文库的构建来举例说明该特征。可以从简单的硒糖苷开始构建由立体化学定义的寡糖组成的具有相当大的结构多样性的文库。该特征已通过构建针对激发子活性寡糖的寡糖文库来举例说明。可以从简单的硒糖苷开始构建由立体化学定义的寡糖组成的具有相当大的结构多样性的文库。通过针对激发子活性寡糖的寡糖文库的构建来举例说明该特征。可以从