(S)-4-Amino-4-methylcarbamoyl-butyric acid benzyl ester | 82594-35-2

• 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: (S)-4-Amino-4-methylcarbamoyl-butyric acid benzyl ester
• 英文别名: Phenylmethyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate；benzyl (4S)-4-amino-5-(methylamino)-5-oxopentanoate
• CAS: 82594-35-2
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: HLGRRQJSYNGKDP-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.58
• 重原子数：
  18.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-4-Amino-4-methylcarbamoyl-butyric acid benzyl ester 在 吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 -L-glutamic acid 1-methylamide 5-benzyl ester
  参考文献：
  名称：

  Studies on Selectin Blockers. 7. Structure−Activity Relationships of Sialyl Lewis X Mimetics Based on Modified Ser-Glu Dipeptides

  摘要：

  We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(x), 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' beta-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(x) mimetics with type II and type II'-beta-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

  DOI：

  10.1021/jm980267x
• 作为产物：
  描述：

  benzyl N-tert-butyloxycarbonyl-L-γ-glutamate α-N-methylamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 (S)-4-Amino-4-methylcarbamoyl-butyric acid benzyl ester
  参考文献：
  名称：

  关于选择阻滞剂的研究。5.基于修饰的丝氨酸-谷氨酸二肽的唾液酸化的Lewis x模拟物的设计，合成和生物学特征。

  摘要：

  我们基于分子模型合理设计了sLe（x）模拟物，合成了II型和II'型β-转二肽（3a，b），并在体外和体内评估了它们的生物学特性。针对E-选择素-sLe（x）结合，II型β-转二肽L-Ser-D-Glu 3a（IC50，13 microM）和II'β-转二肽D-Ser-L-Glu 3b（ IC50（5.5 microM）比sLe（x）（1; IC50，600 microM）和3'-硫酸化Le（x）类似物（2; IC50，280 microM）强效阻滞剂高20-100倍。另一方面，其他立体异构体（例如L-Ser-L-Glu 3c和D-Ser-D-Glu 3d）是非常弱的阻滞剂，3c，d的IC50> 1000 microM。相对于P-和L-选择素，尽管化合物3a-d的立体化学差异很大，但二肽3a-d的阻滞剂均比sLe（x）或化合物2强。在小鼠模型中，化合物3b提供了针对免疫球蛋白E介导的皮肤反

  DOI：

  10.1021/jm970262k

文献信息

• Studies on Selectin Blockers. 6. Discovery of Homologous Fucose Sugar Unit Necessary for E-Selectin Binding
  作者：Yasuyuki Hiramatsu、Hideki Moriyama、Takao Kiyoi、Takahiro Tsukida、Yoshimasa Inoue、Hirosato Kondo

  DOI：10.1021/jm9707481

  日期：1998.6.1

  We describe a mimic of the sugar unit of the E-selectin ligand, sialyl Lewis X (sLe(X)). Carbohydrates are entering the realm of rational drug design, aided by the growing understanding of the structure-function relationships. We investigated a new methodology of preparing sLe(X) mimetics and developed a potent E-selectin blocker characterized by beta-turn dipeptides. Another characteristic point of this E-selectin blocker is that the six-membered fucose ring was replaced with a five-membered fucose ring. Interestingly, it was found that the five-membered fucose ring could also bind to a calcium ion on the E-selectin, which could be an important role of the six-membered fucose ring. Especially, the L-Ser-D-Glu and D-Ser-L-Glu derivatives 3a,b showed 65-90-fold more potent inhibitory activities than the sulfated Le(X) analogue 1. In addition, molecular dynamics (MD) studies indicated that the 2- and 3-OH groups of the six-membered fucose ring, which were necessary for the calcium binding, overlapped well with the 2- and 3-OH groups of the five-membered fucose ring. These new findings could be useful for the design of new types of selectin blockers.
• A stereoselective α-fucosylation reaction using 1-hydroxy donor for the practical synthesis of selectin blocker
  作者：Takao Kiyoi、Hirosato Kondo

  DOI：10.1016/s0960-894x(98)00516-2

  日期：1998.10

  A l-hydroxy 2,3,4-tri-O-benzyl-L-fucose donor affords a high stereoselectivity of glycosylation in the presence of TMSOTf and is a very useful substrate for the preparation of an alpha-L-fucosyl dipeptide in a stereoselective manner. The donor will be a key component in the preparation of an attractively biological selectin blocker 1. (C) 1998 Elsevier Science Ltd. All rights reserved.