N-(9-fluorenylmethoxycarbonyl)-O-(2,3,4,2',3',4',6'-hepta-O-acetyl-β-melibiosyl)-L-serine | 337903-72-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-(9-fluorenylmethoxycarbonyl)-O-(2,3,4,2',3',4',6'-hepta-O-acetyl-β-melibiosyl)-L-serine
• 英文别名: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxypropanoic acid
• CAS: 337903-72-7
• 化学式: C₄₄H₅₁NO₂₂
• 分子量: 945.882
• InChiKey: BEOSITBJMABRIW-ZAASKQLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  67
• 可旋转键数：
  26
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  297
• 氢给体数：
  2
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-苯丙氨酸 、 N-(9-fluorenylmethoxycarbonyl)-O-(2,3,4,2',3',4',6'-hepta-O-acetyl-β-melibiosyl)-L-serine 、 alkaline earth salt of/the/ methylsulfuric acid 生成 Tyr-D-Thr-Gly-Phe-Leu-Ser(β-melibiose)-CONH2
  参考文献：
  名称：

  Biousian glycopeptides penetrate the blood–brain barrier

  摘要：

  Clinicians have long desired the ability to introduce either exogenous or endogenous neuropeptides directly into the brain in order to alter brain chemistry, but have been thwarted by the blood-brain barrier (BBB). The BBB blocks the introduction of most peptides and proteins into the brain. Glycosylation can be employed as an effective and practical strategy that allow the Systemic use of neuropeptides in vivo. A series of glycopeptides based on the Leu-enkephalin analogue YtGFS*-CONH2 led to greatly enhanced stability in vivo and effective penetration of the BBB. Transport through the BBB hinges on the biousian nature of the glycopeptides. That is, the amphipathic glycopeptides possess two conflicting solubility states;, one state that is completely water soluble, and another at water-membrane phase boundaries. Multiple lines of evidence suggest that the BBB transport is absorptive endocytosis. Several Leu-enkephalin analogues studied showed antinociceptive potencies greater than morphine. Moreover, these selective glycopeptides lacked many of the mu-opioid side effects generally associated with classical opiate analgesics. The biousian design was extended to much larger glycopeptides (16-17 residues) related to beta-endorphin, which also penetrated the BBB and produced antinociception in mice. Plasmon-waveguide resonance (PWR) studies showed that the amphipathic helices bound to membrane bilayers with micromolar to low nanomolar K-D's. The presence of diverse endogenous neuropeptide transmitters and neuromodulators in the human brain is potentially applicable to the treatment of a wide ranee of behavioral disorders. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.11.038
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以90%的产率得到N-(9-fluorenylmethoxycarbonyl)-O-(2,3,4,2',3',4',6'-hepta-O-acetyl-β-melibiosyl)-L-serine
  参考文献：
  名称：

  Solid-Phase Synthesis of O-Linked Glycopeptide Analogues of Enkephalin

  摘要：

  The synthesis of 18 N-alpha -FMOC-amino acid glycosides for solid-phase glycopeptide assembly is reported. The glycosides were synthesized either from the corresponding O'Donnell Schiff bases or from N-alpha -FMOC-amino protected serine or threonine and the appropriate glycosyl bromide using Hanessian's modification of the Koenigs-Knorr reaction. Reaction rates of D-glycosyl bromides (e.g., acetobromoglucose) with the L- and D-forms of serine and threonine are distinctly different and can be rationalized in terms of the steric interactions within the two types of diastereomeric transition states for the D/L and D/D reactant pairs. The N-alpha -FMOC-protected glycosides [monosaccharides Xyl, Glc, Gal, Man, GlcNAc, and GalNAc; disaccharides Gal-beta (1-4)-Gle (lactose), Glc-beta-(1-4)-Glc (cellobiose), and Gal-alpha (1-6)-Glc (melibiose)] were incorporated into 22 enkephalin glycopeptide analogues. These peptide opiates bearing the pharmacophore H-Tyr-c[DCys-Gly-PheDCys]- were designed to probe the significance of the glycoside moiety and the carbohydrate-peptide linkage region in blood-brain barrier (BBB) transport, opiate receptor binding, and analgesia.

  DOI：

  10.1021/jo005712m