methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-mannopyranoside | 220129-77-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-mannopyranoside
• 英文别名: methyl 6-azido-6-deoxy-2,3,4-tri-O-benzyl-α-D-mannopyranoside；1-methyl-6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-mannopyranoside；(2R,3R,4S,5S,6S)-2-(azidomethyl)-6-methoxy-3,4,5-tris(phenylmethoxy)oxane
• CAS: 220129-77-1
• 化学式: C₂₈H₃₁N₃O₅
• 分子量: 489.571
• InChiKey: GBNILPPFXNLDEV-MASCHLQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-mannopyranoside 在 乙酸酐 、 三乙胺 、 三苯基膦 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 48.5h， 生成
  参考文献：
  名称：

  A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors

  摘要：

  A library of small molecule heparan sulfate (HS) mimetics was synthesized by employing the Ugi four-component condensation of D-mannopyranoside-derived isocyanides with formaldehyde as the carbonyl component and a selection of carboxylic acids and amines, followed by sulfonation. The library was used to probe the subtle differences surrounding the ionic binding sites of three HS-binding angiogenic growth factors (FGF-1, FGF-2 and VEGF). Each compound features 3 or 4 sulfo groups which serve to anchor the ligand to the HS-binding site of the protein, with a diverse array of functionality in place extending from C-1 or C-6 to probe for adjacent favorable binding interactions. Selectivity of binding to these proteins was clearly observed and supported by molecular docking calculations. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.001
• 作为产物：
  描述：

  methyl 6-O-tosyl-α-D-mannopyranoside 在 sodium azide 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-mannopyranoside
  参考文献：
  名称：

  Towards a stable noeuromycin analog with a d-manno configuration: Synthesis and glycosidase inhibition of d-manno-like tri- and tetrahydroxylated azepanes

  摘要：

  Noeuromycin is a highly potent albeit unstable glycosidase inhibitor due to its hemiaminal function. While stable D-gluco-like analogs have been reported, no data are available for D-manno-like structures. A series of tri- and tetrahydroxylated seven-membered iminosugars displaying either a D-manno-or a L-gulo-like configuration, were synthesized from methyl alpha-D-mannopyranoside using a reductive amination-mediated ring expansion as the key step. Screening towards a range of commercial glycosidases demonstrated their potency as competitive glycosidase inhibitors while cellular assay showed selective albeit weak glycoprotein processing mannosidase inactivation. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.053

文献信息

• Direct CH Amination of Arenes with Alkyl Azides under Rhodium Catalysis
  作者：Kwangmin Shin、Yunjung Baek、Sukbok Chang

  DOI：10.1002/anie.201302784

  日期：2013.7.29

  New horizons in the utility of azides: The rhodium‐catalyzed intermolecular direct CH amination of arenes with alkyl azides provides a convenient route to N‐alkyl anilines (see scheme; DG=directing group). Alkyl azides with a wide range of functional groups reacted readily with various substrates, including benzamides, aromatic ketones, and flavones.

  叠氮化物应用的新视野：用烷基叠氮化物进行铑催化的芳烃分子间直接CH胺化反应可提供一条通往N烷基苯胺的便捷途径（参见方案； DG =导向基团）。具有多种官能团的烷基叠氮化物易于与各种底物反应，包括苯甲酰胺，芳族酮和黄酮。
• Facile fabrication of promising protein tyrosine phosphatase (PTP) inhibitor entities based on ‘clicked’ serine/threonine–monosaccharide hybrids
  作者：Xiao-Peng He、Qiong Deng、Li-Xin Gao、Cui Li、Wei Zhang、Yu-Bo Zhou、Yun Tang、Xiao-Xin Shi、Juan Xie、Jia Li、Guo-Rong Chen、Kaixian Chen

  DOI：10.1016/j.bmc.2011.05.049

  日期：2011.7

  Protein tyrosine phosphatases (PTPs) are well-validated therapeutic targets for many human major diseases. The development of their potent inhibitors has therefore become a main focus of both academia and the pharmaceutical industry. We report herein a facile strategy toward the fabrication of new and competent PTP inhibitor entities by simply ’clicking’ alkynyl amino acids onto diverse azido sugar

  蛋白质酪氨酸磷酸酶（PTP）是许多人类主要疾病的有效治疗靶标。因此，其有效抑制剂的开发已成为学术界和制药业的主要重点。我们在此报告了一种通过简单地将“炔基”氨基酸“点击”到各种叠氮基糖模板上来制造新的胜任的PTP抑制剂实体的简便策略。三唑基葡糖基，半乳糖基和甘露糖基丝氨酸和苏氨酸衍生物可通过点击反应有效地合成，然后被鉴定为对一组经过测试的同源PTP具有选择性的有效CDC25B和PTP1B抑制剂。发现它们的抑制活性和选择性很大程度上取决于在结构和构型上多样化的单糖部分，在该单糖部分上引入了丝氨酸和苏氨酸残基。此外，MTT分析显示三唑连接的糖氨基酸杂合物也可能抑制几种人类癌细胞系的生长，包括A549，Hela，尤其是HCT-116。基于这些令人信服的证据，我们认为该化合物系列可以提供有希望的化学实体，这些新的CDC25B和PTP1B抑制剂具有潜在的细胞活性。此外，从容易获得且具有生物相容性的氨
• Triazole-linked Benzylated Glucosyl, Galactosyl, and Mannosyl Monomers and Dimers as Novel Sugar Scaffold-based PTP1B Inhibitors
  作者：Yin-Jie Zhang、Xiao-Peng He、Cui Li、Zhen Li、De-Tai Shi、Li-Xin Gao、Bei-Ying Qiu、Xiao-Xin Shi、Yun Tang、Jia Li、Guo-Rong Chen

  DOI：10.1246/cl.2010.1261

  日期：2010.12.5

  Monomeric and dimeric benzylated glycosyl benzenes were synthesized via copper-catalyzed [3 + 2] azide–alkyne cycloaddition. These compounds were then identified as protein tyrosine phosphatase (PTP) 1B inhibitors which displayed at least several fold selectivity over other homologous PTPases. The glucosyl, galactosyl, and mannosyl inhibitors exhibited different biological profiles, suggesting the monosaccharides may qualify as chiral scaffolds for probing the spatial preference of PTP1B. Furthermore, docking study suggested a plausible binding mode of this glycoside series with the enzymatic target.

  通过铜催化的[3 + 2]叠氮-炔环加成合成单体和二聚苄基化糖基苯。这些化合物随后被鉴定为蛋白酪氨酸磷酸酶 (PTP) 1B 抑制剂，其选择性比其他同源 PTP 酶至少高出数倍。葡萄糖基、半乳糖基和甘露糖基抑制剂表现出不同的生物学特征，表明单糖可能有资格作为探测 PTP1B 空间偏好的手性支架。此外，对接研究表明该糖苷系列与酶靶点的合理结合模式。
• Synthesis of analogs of 1,1-linked galactosyl mannoside as mimetics of sialyl Lewis X tetrasaccharide
  作者：Kazumi Hiruma、Osamu Kanie、Chi-Huey Wong

  DOI：10.1016/s0040-4020(98)00990-9

  日期：1998.12

  for the incorporation of hydrophobic groups with and without positive or negative charge to position-6 of the mannose residue in the 1,1-linked disaccharide as mimetics of sialyl Lewis X tetrasaccharide in order to enhance binding affinity to selectins.

  已经开发了将带有或不带正电荷或不带正电荷或不带正电荷的疏水基团掺入到1，1-连接的二糖中的甘露糖残基的6位上的方法，以作为唾液酸路易斯X四糖的模拟物，以增强与选择素的结合亲和力。
• Mannose derivatives useful for treating pathologies associated with adherent E. coli
  申请人：ENTEROME

  公开号：US10543223B2

  公开（公告）日：2020-01-28

  The present invention relates to mannose derivatives of formula (I): wherein R1 represents H, CO—(C1-C6)-alkyl or CO-alkylaryl, Y represents a single bond, CH2, O, NR3, S, A represents O, NH or S, X represents H and X′ represents OH or X and X′ taken together with the carbon atom bearing them form a CO group, R2 represents H, a linear or branched (C1-C6)-alkyl or CF3, R3 represents H, a C1-C6 alkyl, a CO—(C1-C6)-alkyl, CF3 or COCF3, and R is as described in claim 1. The mannose derivatives of formulae (I) are useful for treating pathologies associated with the presence of adherent Escherichia coli (AEC), in particular inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis; a urinary tract infection, in particular painful bladder syndrome and cystitis, more particularly interstitial cystitis; irritable bowel syndrome; metabolic diseases such as metabolic obesity, diabetes, hypercholesterolemia; autoimmune inflammatory diseases; and colorectal cancer, in particular colon cancer.

  本发明涉及式 (I) 的甘露糖衍生物： 其中 R1 代表 H、CO-(C1-C6)-烷基或 CO-烷基芳基、 Y 代表单键、CH2、O、NR3、S、 A 代表 O、NH 或 S、 X 代表 H 和 X′ 代表 OH 或 X 和 X′ 与含有它们的碳原子一起构成 CO 基团、 R2 代表 H、直链或支链（C1-C6）-烷基或 CF3、 R3 代表 H、C1-C6 烷基、CO-(C1-C6)-烷基、 或 CO ，以及 R 如权利要求 1 所述。 式（I）的甘露糖衍生物可用于治疗与粘附性大肠杆菌（AEC）的存在有关的病症，特别是炎症性肠病（IBD），如克罗恩病和溃疡性结肠炎；泌尿道感染，特别是膀胱疼痛综合征和膀胱炎，尤其是间质性膀胱炎；肠易激综合征；代谢性疾病，如代谢性肥胖、糖尿病、高胆固醇血症；自身免疫性炎症；以及结肠直肠癌，特别是结肠癌。