methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-galactopyranoside | 88713-84-2

• 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-galactopyranoside
• 英文别名: methyl 6-azido-6-deoxy-2,3,4-tri-O-benzyl-α-D-galactopyranoside；methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-galactoside；(2R,3S,4S,5R,6S)-2-(azidomethyl)-6-methoxy-3,4,5-tris(phenylmethoxy)oxane
• CAS: 88713-84-2
• 化学式: C₂₈H₃₁N₃O₅
• 分子量: 489.571
• InChiKey: GBNILPPFXNLDEV-JYIVOWJTSA-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-galactopyranoside 在 三氟甲磺酸三甲基硅酯 、 硫酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 82.5h， 生成 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-2',3',4'-tri-O-benzyl-6'-deoxy-α-D-galactosyl)-sn-glycerol
  参考文献：
  名称：

  Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay

  摘要：

  In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay. These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line. Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect. We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase. The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.007
• 作为产物：
  描述：

  Α-D-乳酸吡喃糖苷甲酯 在 吡啶 、 4-二甲氨基吡啶 、 sodium azide 、 三氟化硼乙醚 、 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 methyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-galactopyranoside
  参考文献：
  名称：

  Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay

  摘要：

  In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay. These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line. Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect. We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase. The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.007

文献信息

• Synthesis of methyl 2,3-O-glycopyranosylidene-α-d-mannopyranosides having various substituents
  作者：Juji Yoshimura、Katsuji Asano、Kazuyuki Umemura、Shigeomi Horito、Hironobu Hashimoto

  DOI：10.1016/0008-6215(83)84016-6

  日期：1983.9

  title compounds were obtained by condensation of d -glucono-, d -galactono-, or l - glycero - d - gluco -heptono-1,5-lactones with methyl 2,3-di- O -(trimethylsilyl)-α- d -mannopyranosides having various substituents on C-4 and C-6, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst. Except for a 6-acetoxyl group on a lactone component and a ( tert -butyldiphenylsiloxy) group

  摘要标题化合物是通过将d-葡萄糖酸-，d-半乳糖基-或l-甘油-d-葡萄糖-庚基-1,5-内酯与2,3-二甲基O-（三甲基甲硅烷基）-α缩合而获得的。在三甲基甲硅烷基三氟甲磺酸盐作为催化剂的存在下，在C-4和C-6上具有各种取代基的-d-甘露吡喃糖苷。除了内酯组分上的6-乙酰氧基和（叔丁基二苯基甲硅烷氧基）基团外，常用的C-取代基，例如苄氧基，烯丙氧基，叠氮基，酰氧基，（甲硫基）甲氧基和甲氧基，均不能阻止这种情况的发生。缩合。
• Synthesis of (Glycopyranosyl-triazolyl)-purines and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B (PTP1B)
  作者：Lei Luo、Xiao-Peng He、Qiang Shen、Jing-Ya Li、Xiao-Xin Shi、Juan Xie、Jia Li、Guo-Rong Chen

  DOI：10.1002/cbdv.201000242

  日期：2011.11

  majority of these glycoconjugates were good PTP1B inhibitors with IC(50) values in low micromolar range (1.5-11.1 μM). The benzylated sugar derivatives displayed better inhibitory potency than that of the acetylated ones. Replacement of Cl by MeO at C(6) of the purine moiety decreased the inhibition in the case of benzylated (glycosyl-mono-triazolyl)-purines 11 and 12 (IC(50) >80 μM), whereas MeO-substituted

  由于嘌呤和基于嘌呤的核苷均在自然界中显示出广泛的重要生物学活性，因此开发新型嘌呤衍生物引起了人们的极大兴趣。我们在这里报告了这些研究的一个新的扩展，通过将铜或吡喃半乳糖基支架通过Cu（I）催化的Huisgen 1,3-偶极环加成反应引入到6-Cl嘌呤部分的N-或9-位（或两者）。通过这种有效的反应，成功地以高收率成功地合成了一系列糖基-三唑基-嘌呤。生物学评估表明，这些糖缀合物大多数是良好的PTP1B抑制剂，IC（50）值在低微摩尔范围（1.5-11.1μM）之间。苄基糖衍生物显示出比乙酰基糖衍生物更好的抑制能力。在苄基化的（糖基-单-三唑基）-嘌呤11和12（IC（50）> 80μM）的情况下，MeO取代嘌呤部分的C（6）降低了抑制作用，而MeO取代的苄基化的双[半乳糖基-三唑基]-嘌呤16具有最佳的抑制活性，IC（50）值为1.5μM。此外，这些化合物的选择性比其他PTP（TCPTP，
• 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 <i>deoxy</i>-Andrographolide Triazolyl Glycoconjugates for the Treatment of Alzheimer’s Disease
  作者：Surendra Jatav、Nishant Pandey、Pratibha Dwivedi、Ansab Akhtar、Jyoti、Ranjit Singh、Ranju Bansal、Bhuwan B. Mishra

  DOI：10.1021/acschemneuro.2c00328

  日期：2022.12.7

  A new andrographolide-based terminal alkyne 3 was synthesized in good yield from deoxy-andrographolide 2, obtained from a natural compound andrographolide 1, which in turn was isolated from the leaves of the plant Andrographis paniculata. Copper(I)-catalyzed azide–alkyne cycloaddition reaction of alkyne 3 with azido-sugars 4a–f furnished a library of andrographolide-fastened triazolyl glycoconjugates

  一种新的基于穿心莲内酯的末端炔烃3以脱氧-穿心莲内酯2为原料合成，产率高，该天然化合物穿心莲内酯1是从植物穿心莲的叶子中分离得到的。铜（I）催化的炔烃3与叠氮基糖4a-f的叠氮-炔烃环加成反应以良好的收率提供了穿心莲内酯固定的三唑基糖缀合物5a-f库。这些半合成穿心莲内酯衍生物的结构通过傅里叶变换红外、核磁共振和质谱确定。化合物5a–f使用东莨菪碱 (SCOP) 诱导的记忆障碍小鼠模型进一步评估了对阿尔茨海默氏病 (AD) 的影响。据观察，这些化合物的抗氧化和抗胆碱酯酶特性对其改善认知功能的显着潜力有显着贡献。