1,2-di-O-octanoyl-3-O-(N-octanoyl-6'-amino-2',3',4'-tri-O-benzyl-6'-deoxy-α-D-glucopyranosyl)-sn-glycerol | 1383450-10-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: 1,2-di-O-octanoyl-3-O-(N-octanoyl-6'-amino-2',3',4'-tri-O-benzyl-6'-deoxy-α-D-glucopyranosyl)-sn-glycerol
• CAS: 1383450-10-9
• 化学式: C₅₄H₇₉NO₁₀
• 分子量: 902.222
• InChiKey: NLAFOJYOKLCJAY-OUZQBEEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.14
• 重原子数：
  65.0
• 可旋转键数：
  35.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  127.85
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  1,2-di-O-octanoyl-3-O-(N-octanoyl-6'-amino-2',3',4'-tri-O-benzyl-6'-deoxy-α-D-glucopyranosyl)-sn-glycerol 在 20 % Pd(OH)2/C 、 氢气 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 6.0h， 以90%的产率得到1,2-dioctanoyl-3-(N-octeoyl-6'-amino-6'-deoxy-α-D-glucopyranosyl)-sn-glycerol
  参考文献：
  名称：

  Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase

  摘要：

  A glycoglycerolipid 1a isolated from a marine alga showed inhibition to Myt1 kinase with IC50 of 0.12 mu g/mL. We synthesized 1a and its seven analogues (1b-h) in an efficient method with high stereoselectivity. The process employed trichloroacetimidate donor 4b at low substrate concentration to achieve high alpha-selectivity (alpha/beta = 33: 1) in glycosylation reaction. The present synthesis provided various acyl derivatives required for the study on the structure-activity relationship later. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2012.04.005
• 作为产物：
  描述：

  β-1-p-tolylthio-2,3,4-tri-O-benzyl-6-O-tosyl-D-glucopyranose 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 三氟甲磺酸三甲基硅酯 、 水 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 15.58h， 生成 1,2-di-O-octanoyl-3-O-(N-octanoyl-6'-amino-2',3',4'-tri-O-benzyl-6'-deoxy-α-D-glucopyranosyl)-sn-glycerol
  参考文献：
  名称：

  Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase

  摘要：

  A glycoglycerolipid 1a isolated from a marine alga showed inhibition to Myt1 kinase with IC50 of 0.12 mu g/mL. We synthesized 1a and its seven analogues (1b-h) in an efficient method with high stereoselectivity. The process employed trichloroacetimidate donor 4b at low substrate concentration to achieve high alpha-selectivity (alpha/beta = 33: 1) in glycosylation reaction. The present synthesis provided various acyl derivatives required for the study on the structure-activity relationship later. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2012.04.005

文献信息

• Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay
  作者：Alexander Rohe、Christiane Göllner、Kanin Wichapong、Frank Erdmann、Ghassab M.A. Al-Mazaideh、Wolfgang Sippl、Matthias Schmidt

  DOI：10.1016/j.ejmech.2012.06.007

  日期：2013.3

  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.