N-(t-butoxycarbonyl)-L-valyl-D-isoglutamine methyl ester | 73538-10-0

• 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: N-(t-butoxycarbonyl)-L-valyl-D-isoglutamine methyl ester
• 英文别名: t-butoxycarbonyl-L-valyl-D-isoglutamine methyl ester；Boc-Val-D-Glu(OMe)-NH2；Boc-Val-D-Glu(OMe)(OMe)-NH2；methyl (4R)-5-amino-4-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxopentanoate
• CAS: 73538-10-0
• 化学式: C₁₆H₂₉N₃O₆
• 分子量: 359.423
• InChiKey: SQHVDDATLBXKKI-PWSUYJOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(t-butoxycarbonyl)-L-valyl-D-isoglutamine methyl ester 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 15.01h， 生成 N-acetyl-1-O-benzyl-4,6-O-benzylidene-α-muramyl-L-valyl-D-isoglutamine methyl ester
  参考文献：
  名称：

  具有增强佐剂活性的胞壁酰二肽类似物的合成

  摘要：

  N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) 和十三个新的类似物是通过常规有机化学方法合成的，使用二环己基碳二亚胺-N-羟基-5-降冰片烯-2,3-二甲酰亚胺作为偶联剂。测定了它们在豚鼠中诱导对 N-乙酰基-3-(4-arsonophenylazo)-L-酪氨酸的迟发型超敏反应的能力。结果表明，与 MDP 中乳酸部分相邻的 α-氨基酸的存在对于高生物活性很重要，缬氨酸类似物具有最有利的作用。讨论了构效关系。

  DOI：

  10.1246/bcsj.53.2570
• 作为产物：
  描述：

  Boc-D-isoGln-OMe 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 15.25h， 生成 N-(t-butoxycarbonyl)-L-valyl-D-isoglutamine methyl ester
  参考文献：
  名称：

  具有增强佐剂活性的胞壁酰二肽类似物的合成

  摘要：

  N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) 和十三个新的类似物是通过常规有机化学方法合成的，使用二环己基碳二亚胺-N-羟基-5-降冰片烯-2,3-二甲酰亚胺作为偶联剂。测定了它们在豚鼠中诱导对 N-乙酰基-3-(4-arsonophenylazo)-L-酪氨酸的迟发型超敏反应的能力。结果表明，与 MDP 中乳酸部分相邻的 α-氨基酸的存在对于高生物活性很重要，缬氨酸类似物具有最有利的作用。讨论了构效关系。

  DOI：

  10.1246/bcsj.53.2570

文献信息

• Synthesis, and the Adjuvant and Tumor-Suppressive Activities of Quinonyl Muramyl Dipeptides
  作者：Shigeru Kobayashi、Tsunehiko Fukuda、Hidefumi Yukimasa、Masahiko Fujino、Ichiro Azuma、Yuichi Yamamura

  DOI：10.1246/bcsj.57.3182

  日期：1984.11

  ω-(1,4-Benzoquinon-2-yl)alkanoic acids, 2-[10-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)decyl]-3-hydroxytetracosanoic acid, all-trans-5,9,13,17-tetramethyl-4,8,12,16-octadecatetraenoic acid, and stearic acid were coupled to the 6-O-position of the carbohydrate moiety of muramyl dipeptide alkyl esters, and 6-O-aminoacylmuramyl dipeptide methyl esters. The aminoacyl residues used were Gly, Leu, Ahx, and Aud. New synthetic methods were developed for ω-(1,4-benzoquinon-2-yl)alkanoic acids such as 22-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)docosanoic acid, and the α-branched ω-(1,4-benzoquinone-2-yl) β-hydroxy acid, 2-[10-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)decyl]-3-hydroxytetracosanoic acid. The effects of the resulting quinonyl, multiprenylacetyl, and stearoylmuramyl dipetides on the induction of delayed-type hypersensitivity to ABA-Tyr in guinea pigs and the tumor(meth-A)-suppressive activity in syngeneic BALB/c female mice were measured. The results revealed that all these muramyl-dipeptide derivatives retained the adjuvant activity whereas the potent tumor-suppressive activity was observed only in quinonylmuramyl dipeptides, indicating that the 5,6-dimethoxy-3-methyl-1,4-benzoquinone ring is a requisite for the manifestation of the tumor-suppressive activity. The lipophilicity-hydrophilicity balance of the molecule was also important. Among the compounds tested, N-acetyl-6-O-[10-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)decanoyl]muramyl-l-valyl-d-isoglutamine methyl ester showed the most potent tumor-suppressive activity. This compound also showed tumor-regressive activity in guinea pigs, and hence is a good candidate for further studies.

  ω-(1,4-苯醌-2-基)烷酸、2-[10-(5,6-二甲氧基-3-甲基-1,4-苯并苯醌-2-基)癸基]-3-羟基二十四面酸、全反式-5,9,13,17-四甲基-4,8,12,16-十八碳四烯酸和硬脂酸被偶联到脂质双肽 muramyl dipeptide 的糖部分6-O位置上，形成了6-O-酰氨基muramyl dipeptide甲酯。所使用的酰氨基残基为甘氨酸、亮氨酸、己二酸和叔丁基胺。开发了新的合成方法来制备ω-(1,4-苯醌-2-基)烷酸，如22-(5,6-二甲氧基-3-甲基-1,4-苯醌-2-基)二十二酸，以及α-分支的ω-(1,4-苯醌-2-基)β-羟基酸，即2-[10-(5,6-二甲氧基-3-甲基-1,4-苯醌-2-基)癸基]-3-羟基二十四酸。测定了这些醌基、多烯丙基乙酰基和硬脂酰基muramyl dipeptide在诱导豚鼠对ABA-酪氨酸迟发型超敏反应和抑制同系BALB/c雌性小鼠肿瘤(meth-A)活性中的作用。结果表明，所有这些muramyl dipeptide衍生物都保留了佐剂活性，而只有醌基muramyl dipeptides显示出较强的肿瘤抑制活性，表明5,6-二甲氧基-3-甲基-1,4-苯醌环对于显现肿瘤抑制活性是必需的。分子的亲脂性-亲水性平衡也很重要。在所测试的化合物中，N-乙酰基-6-O-[10-(5,6-二甲氧基-3-甲基-1,4-苯醌-2-基)癸酰基]muramyl-l-缬氨酸-d-异谷氨酰胺甲酯显示出最强的肿瘤抑制活性。该化合物在豚鼠中也显示出肿瘤退缩活性，因此是一个有前景的研究候选物。
• Glucosamine peptide derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04369178A1

  公开（公告）日：1983-01-18

  Novel glucosamine-peptide derivatives of the formula: ##STR1## wherein m is 0 or 1; n is 0 or an integer of 1 to 9; R is lower alkyl which may be substituted with hydroxyl, or aryl; R.sup.1 is hydrogen or acyl having an acyclic hydrocarbon group, the terminal of which may be substituted with a cyclic hydrocarbon group directly, via a carbonyl group or via an oxygen atom; provided that when R.sup.1 is hydrogen m is 1; R.sup.2 is hydrogen or lower alkyl which may form a ring by connecting its terminal with the .alpha.-nitrogen atom when n is 0, or hydrogen when n is an integer of 1 to 9; R.sup.3 is hydrogen or lower alkyl; R.sup.4 and R.sup.5 are each hydrogen or lower alkyl which may be substituted with hydroxyl or benzyloxyl; R.sup.6 is hydrogen or lower alkyl; R.sup.7 is alkyl which may be substituted with lower alkoxyl or aralkyl; R.sup.8 and R.sup.9 are each hydrogen, lower alkyl or aralkyl; and (D) and (L) each indicate configurations if their respective carbon atoms are asymmetric; or an acid addition salt thereof, have immunostimulatory activity.

  新型葡萄糖胺-肽衍生物的化学式如下：##STR1## 其中m为0或1；n为0或1至9的整数；R为可以用羟基取代的低碳烷基，或芳基；R.sup.1为氢或酰基，具有一个线性碳氢基团，其末端可以直接或通过羰基或氧原子与一个环烃基团相连；当R.sup.1为氢时，m为1；R.sup.2为氢或可以通过将其末端与α-氮原子连接而形成环的低碳烷基，或当n为1至9的整数时为氢；R.sup.3为氢或低碳烷基；R.sup.4和R.sup.5分别为氢或可以用羟基或苄氧基取代的低碳烷基；R.sup.6为氢或低碳烷基；R.sup.7为可以用低碳烷氧基或芳基取代的烷基；R.sup.8和R.sup.9分别为氢、低碳烷基或芳基；(D)和(L)分别表示它们各自的碳原子具有对映异构体；或其酸盐加合物具有免疫刺激活性。
• Novel quinonyl derivatives of muramyl dipeptide possessing potent antitumor activity.
  作者：SHIGERU KOBAYASHI、TSUNEHIKO FUKUDA、ISUKE IMADA、MASAHIKO FUJINO、ICHIRO AZUMA、YUICHI YAMAMURA

  DOI：10.1248/cpb.27.3193

  日期：——

  Three novel quinonyl muramyldipeptides, 2-2-acetamido-2-deoxy-6-O-[10-(2, 3-dimethoxy-5-methyl-1, 4-benzoquinon-6-yl) decanoyl]-D-glucopyranos-3-O-yl}-D-propionyl-L-valyl-D-isoglutamine methyl ester (1a) and its Ser and Thr analogues (1b and 1c), were synthesized and their antitumor effects on the suppression of tumor growth in syngeneic mice were assayed. Among these compounds, 1a showed the most potent antitumor activity.

  研究人员合成了三种新型醌基喃喃二肽--2-2-乙酰氨基-2-脱氧-6-O-[10-(2, 3-二甲氧基-5-甲基-1, 4-苯醌-6-基)癸酰基]-D-吡喃葡萄糖-3-O-基}-D-丙酰基-L-缬氨酰基-D-异谷氨酰胺甲酯（1a）及其 Ser 和 Thr 类似物（1b 和 1c）、合成了这些化合物，并检测了它们对抑制合成小鼠肿瘤生长的抗肿瘤作用。在这些化合物中，1a 的抗肿瘤活性最强。
• Glucosamine-peptide derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0014984B1

  公开（公告）日：1982-12-01
• US4369178A
  申请人：——

  公开号：US4369178A

  公开（公告）日：1983-01-18