L-2-Aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate | 112302-93-9

• 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: L-2-Aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate
• CAS: 112302-93-9
• 化学式: C₂HF₃O₂*C₁₆H₂₃N₃O₄
• 分子量: 435.4
• InChiKey: BQKKHMSPNWQNNR-JHEYCYPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.85
• 重原子数：
  30.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  161.81
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  Tert-butoxycarbonyl-L-2-aminobutanoyl-D-isoglutamine benzyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 生成 L-2-Aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate
  参考文献：
  名称：

  O- [2-乙酰氨基-2-脱氧-6-O-硬脂酰基-和-6-O-（2-十四烷基十六烷酰基）-β-D-吡喃葡萄糖基]-（1-> 4）-N-乙酰基去甲酰基-的合成L-α-氨基丁酰基-D-异谷氨酰胺，MDP的亲脂性二糖类似物。

  摘要：

  12的部分O-酰化和保护基的氢解分别得到6-O-硬脂酰基-和6-O-（2-十四烷基十六烷酰基）-二糖-二肽。据报道在细胞介导的免疫中有热原性和佐剂活性。

  DOI：

  10.1016/0008-6215(94)84291-4

文献信息

• Synthesis of Normuramic Acid Carba Analog and Its Glycopeptide Derivative Resistant to β-Elimination Splitting of the Side Chain
  作者：Miroslav Ledvina、Radka Pavelová、Anna Rohlenová、Jan Ježek、David Šaman

  DOI：10.1135/cccc20001726

  日期：——

  Carba analogs of normuramic acid, i.e., 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid derivatives (nitrile or esters) 3a-3c were prepared by addition of radicals generated from benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-[(methylsulfanyl)thiocarbonyl]- (2a) or -3-O-(phenoxythiocarbonyl)-α-D-glucopyranoside (2b) with Bu₃SnH to acrylonitrile or acryl esters. Alkaline hydrolysis of ethyl ester 3c afforded 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid (5). Coupling of acid 5 with L-2-aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate and subsequent deprotection of the intermediate 6 furnished N-[3-(2-acetamido-2,3-dideoxy-α-D-glucopyranosid-3-yl)propanoyl]-L-2-aminobutanoyl-D-isoglutamine (7).

  对应的中文翻译如下：

  通过将从苯甲酰 2-乙酰氨基-2-去氧-4,6-O-异丙基-3-O-[(甲硫基)硫代羰基]- (2a) 或-3-O-(苯氧硫代羰基)-α-D-葡萄糖吡喃糖苷 (2b) 生成的自由基加入到丙烯腈或丙烯酯中，制备了正摩尔酸的卡巴类似物，即 3-(苯甲酰 2-乙酰氨基-2,3-二去氧-4,6-O-异丙基-α-D-葡萄糖吡喃糖苷-3-基)丙酸衍生物 (腈或酯) 3a-3c。对乙酯 3c 进行碱水解得到 3-(苯甲酰 2-乙酰氨基-2,3-二去氧-4,6-O-异丙基-α-D-葡萄糖吡喃糖苷-3-基)丙酸 (5)。将酸 5 与 L-2-氨基丁酰-D-异谷氨酸苄酯三氟乙酸酯偶联，然后去保护中间体 6 得到 N-[3-(2-乙酰氨基-2,3-二去氧-α-D-葡萄糖吡喃糖苷-3-基)丙酰]-L-2-氨基丁酰-D-异谷氨酸 (7)。

• Synthesis and Immunomodulating Activity of Lipophilic Analogs of N-Acetylnormuramoyl-L-2-aminobutanoyl-D-isoglutamine
  作者：Miroslav Ledvina、Jan Ježek、David Šaman、Věra Hříbalová

  DOI：10.1135/cccc19980590

  日期：——

  N-Acetylnormuramoyl-L-2-aminobutanoyl-D-isoglutamine (7) and its lipophilic 6-O-octadecanoyl (8) and 6-O-(2-tetradecylhexadecanoyl) (9) derivatives were prepared and their immunoadjuvant activity and pyrogenicity were tested. Compounds 8 and 9 are less pyrogenic than muramoyl-dipeptide (MDP) and norMDP analog 7. Both lipophilic derivatives 8 and 9 are better adjuvants than MDP in cell mediated immunity.

  翻译结果： N-乙酰基诺鲁酰-L-2-氨基丁酰-D-异谷氨酸肽（7）及其亲脂性6- O-十八烷酰（8）和6- O-（2-十四烷基十六烷酰）（9）衍生物已制备，并测试了它们的免疫佐剂活性和致热原性。化合物8和9的致热原性比Muramoyl-dipeptide（MDP）和norMDP类似物7低。在细胞介导的免疫中，两种亲脂性衍生物8和9都比MDP更好的佐剂。
• 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).