benzyl (R)-4-((S)-2-((R)-2-(((4aR,6S,7R,8R,8aS)-7-acetamido-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy)propanamido)propanamido)-5-amino-5-oxopentanoate | 69323-69-9

• 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: benzyl (R)-4-((S)-2-((R)-2-(((4aR,6S,7R,8R,8aS)-7-acetamido-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy)propanamido)propanamido)-5-amino-5-oxopentanoate
• 英文别名: γ-benzyl ester of O-(benzyl 2-acetamido-4,6-O-isopropylidene-2-deoxy-α-D-glucopyranosid-3-yl)-D-lactoyl-L-alanyl-D-isoglutamine；benzyl (4R)-4-[[(2S)-2-[[(2R)-2-[[(4aR,6S,7R,8R,8aS)-7-acetamido-2,2-dimethyl-6-phenylmethoxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propanoyl]amino]propanoyl]amino]-5-amino-5-oxopentanoate
• CAS: 69323-69-9；75263-32-0；75283-18-0；77843-23-3；128779-65-7
• 化学式: C₃₆H₄₈N₄O₁₁
• 分子量: 712.797
• InChiKey: ACNVDFRQSSUSLF-OLCQQDSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  51
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  203
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  benzyl (R)-4-((S)-2-((R)-2-(((4aR,6S,7R,8R,8aS)-7-acetamido-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy)propanamido)propanamido)-5-amino-5-oxopentanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以73%的产率得到benzyl N²-(N-acetyl-1-O-benzyl-α-D-muramoyl)-L-alanyl-D-isoglutaminate
  参考文献：
  名称：

  Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

  摘要：

  Porphyromonas gingivalis (P.g.)-induced TNF-alpha can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 mu g/mL of MDP (MDP-low) up-regulated TNF-alpha by 29%, while 100 mu g/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF-alpha induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4.

  DOI：

  10.1021/acs.jmedchem.6b00681
• 作为产物：
  描述：

  N-benzyloxycarbonyl-D-glutamic acid 在 2,2,6,6-四甲基哌啶 、 N-羟基-7-氮杂苯并三氮唑 、 palladium 10% on activated carbon 、 氨 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 132.42h， 生成 benzyl (R)-4-((S)-2-((R)-2-(((4aR,6S,7R,8R,8aS)-7-acetamido-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy)propanamido)propanamido)-5-amino-5-oxopentanoate
  参考文献：
  名称：

  Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

  摘要：

  Porphyromonas gingivalis (P.g.)-induced TNF-alpha can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 mu g/mL of MDP (MDP-low) up-regulated TNF-alpha by 29%, while 100 mu g/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF-alpha induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4.

  DOI：

  10.1021/acs.jmedchem.6b00681

文献信息

• ZEMLYAKOV, A. E.;CHIRVA, V. YA., XIMIYA PRIROD. SOED.,(1988) N, S. 892-893
  作者：ZEMLYAKOV, A. E.、CHIRVA, V. YA.

  DOI：——

  日期：——
• Synthesis of the γ-octadecylamide of N-acetylmuramoyl-L-alanyl-D-isoglutamine
  作者：A. E. Zemlyakov、V. Ya. Chirva

  DOI：10.1007/bf00598215

  日期：1988.11