N-[2-O-(benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-stearoylamino-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2,3-dideoxy-α-D-glucopyranosid-3-yl)-glycoloyl]-L-α-aminobutanoyl-D-isoglutaminyl benzyl ester | 141989-33-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[2-O-(benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-stearoylamino-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2,3-dideoxy-α-D-glucopyranosid-3-yl)-glycoloyl]-L-α-aminobutanoyl-D-isoglutaminyl benzyl ester
• 英文别名: benzyl (4R)-4-[[(2S)-2-[[2-[(2S,3R,4R,5S,6R)-3-acetamido-5-[(2S,3R,4R,5S,6R)-3-(octadecanoylamino)-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxy-2-phenylmethoxy-6-(phenylmethoxymethyl)oxan-4-yl]oxyacetyl]amino]butanoyl]amino]-5-amino-5-oxopentanoate
• CAS: 141989-33-5
• 化学式: C₈₅H₁₁₃N₅O₁₆
• 分子量: 1460.86
• InChiKey: NMQJDBMCQWONOC-WFINMUDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.67
• 重原子数：
  106.0
• 可旋转键数：
  50.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  268.86
• 氢给体数：
  5.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  N-[2-O-(benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-stearoylamino-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2,3-dideoxy-α-D-glucopyranosid-3-yl)-glycoloyl]-L-α-aminobutanoyl-D-isoglutaminyl benzyl ester 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 反应 15.0h， 以70%的产率得到O-(2-deoxy-2-stearoylamino-β-D-glucopyranosyl)-(1<*>4)-N-acetylnormuramoyl-L-α-aminobutanoyl-D-isoglutamine
  参考文献：
  名称：

  Synthesis of O-(2-Deoxy-2-stearoylamino-β-D-glucopyranosyl)-(1→4)-N-acetylnormuramoyl-L-α-aminobutanoyl-D-isoglutamine, a Lipophilic Disaccharide Analogue of MDP

  摘要：

  用氢氧化钡部分去乙酰化化合物II，得到苯甲醇2-乙酰氨基-3-O-烯丙基-4-O-(2-氨基-2-脱氧-4,6-O-异丙基-β-D-葡萄糖吡喃糖基)-6-O-苯甲醇-2-脱氧-α-D-葡萄糖吡喃糖苷(III)，产率高。在DCC存在下，化合物III被N酰化为硬脂酸酯，得到苯甲醇2-乙酰氨基-6-O-苯甲醇-3-O-羧甲基-2-脱氧-4-O-(3,4,6-三-O-苯甲醇-2-硬脂酰氨基-β-D-葡萄糖吡喃糖基)-α-D-葡萄糖吡喃糖苷(VII)。将化合物VII与L-α-氨基丁酰-D-异谷氨酸苯甲酯偶联，随后氢解产物VIII得到化合物IX。

  DOI：

  10.1135/cccc19920579
• 作为产物：
  描述：

  L-2-Aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate 、 benzyl 2-acetamido-6-O-benzyl-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-stearoylamino-β-D-glucopyranosyl)-2-deoxy-3-O-carboxymethyl-α-D-glucopyranoside 在 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 N-[2-O-(benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-stearoylamino-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2,3-dideoxy-α-D-glucopyranosid-3-yl)-glycoloyl]-L-α-aminobutanoyl-D-isoglutaminyl benzyl ester
  参考文献：
  名称：

  Synthesis of O-(2-Deoxy-2-stearoylamino-β-D-glucopyranosyl)-(1→4)-N-acetylnormuramoyl-L-α-aminobutanoyl-D-isoglutamine, a Lipophilic Disaccharide Analogue of MDP

  摘要：

  用氢氧化钡部分去乙酰化化合物II，得到苯甲醇2-乙酰氨基-3-O-烯丙基-4-O-(2-氨基-2-脱氧-4,6-O-异丙基-β-D-葡萄糖吡喃糖基)-6-O-苯甲醇-2-脱氧-α-D-葡萄糖吡喃糖苷(III)，产率高。在DCC存在下，化合物III被N酰化为硬脂酸酯，得到苯甲醇2-乙酰氨基-6-O-苯甲醇-3-O-羧甲基-2-脱氧-4-O-(3,4,6-三-O-苯甲醇-2-硬脂酰氨基-β-D-葡萄糖吡喃糖基)-α-D-葡萄糖吡喃糖苷(VII)。将化合物VII与L-α-氨基丁酰-D-异谷氨酸苯甲酯偶联，随后氢解产物VIII得到化合物IX。

  DOI：

  10.1135/cccc19920579

文献信息

• Nonpyrogenic Molecular Adjuvants Based on norAbu-Muramyldipeptide and norAbu-Glucosaminyl Muramyldipeptide: Synthesis, Molecular Mechanisms of Action, and Biological Activities in Vitro and in Vivo
  作者：Roman Effenberg、Pavlína Turánek Knötigová、Daniel Zyka、Hana Čelechovská、Josef Mašek、Eliška Bartheldyová、František Hubatka、Štěpán Koudelka、Róbert Lukáč、Anna Kovalová、David Šaman、Michal Křupka、Lucia Barkocziova、Petr Kosztyu、Marek Šebela、Ladislav Drož、Michal Hučko、Mária Kanásová、Andrew D. Miller、Milan Raška、Miroslav Ledvina、Jaroslav Turánek

  DOI：10.1021/acs.jmedchem.7b00593

  日期：2017.9.28

  Fatty acyl analogues of muramyldipeptide (MDP) (abbreviated N-L18 norAbuGMDP, N-B30 norAbuGMDP, norAbuMDP-Lys(L18), norAbuMDP-Lys(B30), norAbuGMDP-Lys(L18), norAbuGMDP-Lys(B30), B30 norAbuMDP, L18 norAbuMDP) are designed and synthesized comprising the normuramyl-L-alpha-aminobutanoyl (norAbu) structural moiety. All new analogues show depressed pyrogenicity in both free (micellar) state and in liposomal formulations when tested in rabbits in vivo (sc and iv application). New analogues are also shown to be selective activators of NOD2 and NLRP3 (inflammasome) in vitro but not NOD1. Potencies of NOD2 and NLRP3 stimulation are found comparable with free MDP and other positive controls. Analogues are also demonstrated to be effective in stimulating cellular proliferation when the sera from mice are injected sc with individual liposome-loaded analogues, causing proliferation of bone marrow-derived GM-progenitors cells. Importantly, vaccination nanoparticles prepared from metallochelation liposomes, His-tagged antigen rOspA from Borrelia burgdorferi, and lipophilic analogue norAbuMDP-Lys(B30) as adjuvant, are shown to provoke OspA-specific antibody responses with a strong Th1-bias (dominance of IgG2a response). In contrast, the adjuvant effects of Alum or parent MDP show a strong Th2-bias (dominance of IgG1 response).