benzyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside | 112302-95-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside
• 英文别名: Benzyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-beta-D-glucopyranosyl-(1->4)-2-acetamido-6-O-benzyl-2-deoxy-3-O-(meth oxycarbonyl)methyl-alpha-D-glucopyranoside；methyl 2-[(2S,3R,4R,5S,6R)-3-acetamido-5-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxy-2-phenylmethoxy-6-(phenylmethoxymethyl)oxan-4-yl]oxyacetate
• CAS: 112302-95-1
• 化学式: C₅₄H₆₂N₂O₁₃
• 分子量: 947.092
• InChiKey: RVQNCIIVCYLLIT-BLHRGRIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  69
• 可旋转键数：
  25
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  168
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2-脱氧-2-苯二酰亚胺-1,3,4,6-四-氧-乙酰-β-D-吡喃葡萄糖 在 barium dihydroxide 、 Wilkinson's catalyst 、 甲酸 、 氢溴酸 、 sodium methylate 、 silver trifluoromethanesulfonate 、 sodium hydride 、 正丁胺 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.83h， 生成 benzyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl-(1→4)-2-acetamido-6-O-benzyl-2-deoxy-3-O-(methoxycarbonyl)methyl-α-D-glucopyranoside
  参考文献：
  名称：

  O-（2-乙酰氨基-2-脱氧-β-d-吡喃葡萄糖基）-（1→4）-N-乙酰基去甲基尿嘧啶-1-α-氨基丁酰基-d-异谷氨酰胺的合成

  摘要：

  摘要苄基2-乙酰氨基-3- O-烯丙基-6- O-苄基-2-脱氧-4- O-（3,4,6-三-O-乙酰基-2-脱氧-2-邻苯二甲酰亚胺-β-d在不存在碱的情况下使用三氟甲磺酸银方法以高收率获得-（吡喃葡萄糖基）-α-d-吡喃葡萄糖苷（4）。化合物4经六步转化为苄基2-乙酰氨基-4-O-（2-乙酰氨基-3,4,6-三-O-苄基-2-脱氧-β-d-吡喃葡萄糖基）-6-O-苄基将-3-O-（羧甲基）-2-脱氧-α-d-吡喃葡萄糖苷与1-α-氨基丁酰基-d-异谷氨酰胺的苄基酯偶联，并将产物进行氢水解，得到标题化合物。苄基2-乙酰氨基-4- O-（2-乙酰氨基-2-脱氧-β-d-吡喃葡萄糖基）的O-苄基化-3-O-烯丙基-6-O-苄基-2-脱氧-α-d-吡喃葡萄糖苷通过对反应混合物进行超声处理，大大增强了用苄基溴和氢氧化钡在N，N-二甲基甲酰胺中的抗氧化剂。

  DOI：

  10.1016/0008-6215(87)80165-9

文献信息

• Normuramyl glycopeptide compounds
  申请人：Hipler Karsten

  公开号：US08653049B2

  公开（公告）日：2014-02-18

  The invention provides a compound (which can act as an adjuvant) of Formula I or Formula (II), wherein R1 R4 R5 R6 and R7 are each independently selected from hydrogen, acetyl, hydrocarbyl, a lipid moiety and a lipid acyl moiety; R2 is a hydroxyl, a hydrocarbyl, a lipid moiety, a lipid acyl moiety; or an amino hydrocarbyl group optionally substituted with a hydrocarbyl, a lipid moiety or a lipid acyl moiety; R3 and R8 are each independently selected from acetyl, a hydrocarbyl, a lipid moiety and a lipid acyl moiety; X is a peptide chain; The above normuramylglycopeptide compounds can be located in liposomes and micelles and can function as immunomodulators, along with a desired antigen (or DNA encloding the antigen), in (e.g. DNA) vaccines.

  本发明提供了一种化合物（可作为佐剂），其化学式为I或II式，其中R1、R4、R5、R6和R7各自独立地选自氢、乙酰基、烃基、脂质基团和脂肪酰基团；R2为羟基、烃基、脂质基团、脂肪酰基团或者是氨基烃基团，该氨基烃基团可选择性地被氢、脂质基团或脂肪酰基团取代；R3和R8各自独立地选自乙酰基、烃基、脂质基团和脂肪酰基团；X为肽链。上述诺莫拉姆基糖肽化合物可以位于脂质体和胶束中，并可以作为免疫调节剂与所需的抗原（或DNA编码抗原）一起在（例如DNA）疫苗中发挥作用。
• COMPOUND
  申请人：Hipler Karsten

  公开号：US20110002983A1

  公开（公告）日：2011-01-06

  The invention provides a compound (which can act as an adjuvant) of Formula I or Formula (II), wherein R 1 R 4 R 5 R 6 and R 7 are each independently selected from hydrogen, acetyl, hydrocarbyl, a lipid moiety and a lipid acyl moiety; R 2 is a hydroxyl, a hydrocarbyl, a lipid moiety, a lipid acyl moiety; or an amino hydrocarbyl group optionally substituted with a hydrocarbyl, a lipid moiety or a lipid acyl moiety; R 3 and R 8 are each independently selected from acetyl, a hydrocarbyl, a lipid moiety and a lipid acyl moiety; X is a peptide chain; The above normuramylglycopeptide compounds can be located in liposomes and micelles and can function as immunomodulators, along with a desired antigen (or DNA encloding the antigen), in (e.g. DNA) vaccines.

  本发明提供了一种化合物（可以作为佐剂），其化学式为I或II式，其中R1R4R5R6和R7各自独立地选择氢、乙酰、烃基、脂质基团和脂肪酰基团；R2为羟基、烃基、脂质基团、脂肪酰基团或者是氨基烃基，该氨基烃基可以选择性地取代烃基、脂质基团或脂肪酰基团；R3和R8各自独立地选择乙酰、烃基、脂质基团和脂肪酰基团；X为肽链。上述诺莫拉葡肽化合物可以位于脂质体和胶束中，并且可以与所需的抗原（或DNA编码抗原）一起在（例如DNA）疫苗中作为免疫调节剂发挥作用。
• 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).