L-丙氨酰-D-谷氨酸二苄基酯盐酸盐 | 63092-23-9

• 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
• 中文名称: L-丙氨酰-D-谷氨酸二苄基酯盐酸盐
• 英文名称: L-alanyl-D-glutamic acid dibenzyl ester hydrochloride
• 英文别名: dibenzyl L-alanyl-D-glutamate hydrochloride；dibenzyl (2R)-2-[[(2S)-2-aminopropanoyl]amino]pentanedioate;hydrochloride
• CAS: 63092-23-9
• 化学式: C₂₂H₂₆N₂O₅*ClH
• 分子量: 434.92
• InChiKey: LWNBKQUYNNTHCG-ZKKBRJJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-丙氨酰-D-谷氨酸二苄基酯盐酸盐 在 palladium on activated charcoal 叠氮磷酸二苯酯 、 氢气 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 62.0h， 生成 (R)-2-{(S)-2-[2-(2-Acetylamino-cyclohexyloxy)-acetylamino]-propionylamino}-pentanedioic acid
  参考文献：
  名称：

  N-{trans-2-[[2‘-(Acetylamino)cyclohexyl]oxy]acetyl}-l-alanyl-d-glutamic Acid:  A Novel Immunologically Active Carbocyclic Muramyl Dipeptide Analogue

  摘要：

  A novel non-pyrogenic carbocyclic muramyl dipeptide (MDP) analogue, N-(trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl)-L-alanyl-D-glutamic acid, was obtained by replacement of the N-acetylmuramic acid part and the D-isoglutamine residue of the MDP molecule by a trans2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl moiety and D-glutamic acid, respectively. The title compound was selected as a promising candidate for further evaluation among several related analogues on the basis of an immunorestoration test in mice. This novel nor-MDP analogue protects mice against the immunosuppressive effect of cyclophosphamide and increases the nonspecific resistance of mice against fungal infection. It is an immunomodulator which enhances the maturation of lymphocytes B to plasma cells and increases the activity of lymphocytes B and lymphocytes T as well as that of macrophages but does not alter the number of these cells.

  DOI：

  10.1021/jm970509d

文献信息

• N-acyldipeptides, processes for the preparation thereof and
  申请人：——

  公开号：US05514654A1

  公开（公告）日：1996-05-07

  N-acyldipeptides of formula I ##STR1## wherein R represents a rest of formula ##STR2## and R.sub.4, Y, m, n and Z have the meaning as defined in the description, R.sub.1 represents hydrogen, a 1-10 C. alkyl, an optionally substituted methyl or benzyl, R.sub.2 represents a --CO--A group, wherein A has the meanings as defined in the description, R.sub.3 represents a --(CH.sub.2).sub.p --CO--W group, wherein p and W have the meaning as defined in the description.

  公式I的N-酰基二肽，其中R代表公式中的余项，R.sub.4、Y、m、n和Z的含义如描述中定义，R.sub.1代表氢、1-10碳的烷基、可选取代的甲基或苄基，R.sub.2代表一个--CO--A基团，其中A的含义如描述中定义，R.sub.3代表一个--(CH.sub.2).sub.p--CO--W基团，其中p和W的含义如描述中定义。
• Trans-2-acylaminocyclohexyloxyacyldipeptides in the form of mixtures of
  申请人：Univerza Edvarda Kardelja v Ljubljana

  公开号：US05231216A1

  公开（公告）日：1993-07-27

  There are described novel trans-2-acylaminocyclohexyloxyacyldipeptides of formula I ##STR1## wherein R.sub.1 represents --CO--R.sub.6, --SO.sub.2 --R.sub.7 or ##STR2## R.sub.6 is C.sub.1 -C.sub.18 alkyl or C.sub.1 -C.sub.18 alkoxy, R.sub.7 is C.sub.1 -C.sub.18 alkyl or an optionally substituted phenyl group, Y is .dbd.O, .dbd.S or .dbd.NH; R.sub.2 =R.sub.3 and represent --H or C.sub.1 -C.sub.12 alkyl, R.sub.4 represents --OR.sub.8 or --NHR.sub.9, R.sub.8 is --H, C.sub.1 -C.sub.8 alkyl or benzyl, R.sub.9 is --H, a straight or branched chain C.sub.1 -C.sub.18 alkyl group or benzyl group; R.sub.5 represents --OR.sub.9 or --NHR.sub.9, and novel (1R,2R)- and (1S,2S)-trans-2-acylaminocyclohexyloxyacetyldipeptides of the formulas Ia and Ib ##STR3## wherein R.sub.1 is --CO--R.sub.6, R.sub.6 is C.sub.1 -C.sub.18 alkyl, R.sub.2 is --H, R.sub.3 is --H or C.sub.1 -C.sub.12 alkyl, R.sub.4 is --OR.sub.8 or --NHR.sub.9, R.sub.8 is --H, C.sub.1 -C.sub.8 alkyl or benzyl, R.sub.9 is --H, C.sub.1 -C.sub.18 alkyl or benzyl, R.sub.5 is --OR.sub.9 or --NHR.sub.9 Compounds of formula I, Ia and Ib and the pharmaceutically acceptable alkali salts thereof show immunomodulatory and antitumour activities and can be used in the preparation of medicaments.

  描述了一种新型的trans-2-acylaminocyclohexyloxyacyldipeptides，其化学式为I ##STR1## 其中R.sub.1代表--CO--R.sub.6，--SO.sub.2 --R.sub.7或##STR2## R.sub.6是C.sub.1 -C.sub.18烷基或C.sub.1 -C.sub.18烷氧基，R.sub.7是C.sub.1 -C.sub.18烷基或一个可选择替代的苯基，Y是.dbd.O，.dbd.S或.dbd.NH；R.sub.2 =R.sub.3代表--H或C.sub.1 -C.sub.12烷基，R.sub.4代表--OR.sub.8或--NHR.sub.9，R.sub.8是--H，C.sub.1 -C.sub.8烷基或苄基，R.sub.9是--H，一种直链或支链C.sub.1 -C.sub.18烷基或苄基；R.sub.5代表--OR.sub.9或--NHR.sub.9，以及新型的(1R,2R)-和(1S,2S)-trans-2-acylaminocyclohexyloxyacetyldipeptides，其化学式为Ia和Ib ##STR3## 其中R.sub.1是--CO--R.sub.6，R.sub.6是C.sub.1 -C.sub.18烷基，R.sub.2是--H，R.sub.3是--H或C.sub.1 -C.sub.12烷基，R.sub.4是--OR.sub.8或--NHR.sub.9，R.sub.8是--H，C.sub.1 -C.sub.8烷基或苄基，R.sub.9是--H，C.sub.1 -C.sub.18烷基或苄基，R.sub.5是--OR.sub.9或--NHR.sub.9，化合物I、Ia和Ib及其药学上可接受的碱盐显示出免疫调节和抗肿瘤活性，可用于药物的制备。
• Synthesis of Phthalimido-Desmuramylpeptide Analogues as Potential Immunomodulating Agents
  作者：Uroš Urleb、Aleš Krbavčič、Marija Sollner、Danijel Kikelj、Slavko Pečar

  DOI：10.1002/ardp.19953280204

  日期：——

  The preparation of immunologically active phthalimido desmuramylpeptide analogues 2e‐h, 4c‐d, and 7b is described. The N‐acetylmuramic acid in the muramyl dipeptide has been replaced by a phthaloylated acyclic moiety such as N‐phthaloylated amino acids 1a–c, 2‐(2‐phthalimidoethoxy)acetic acid 3, or by the carbocyclic rac. trans‐2‐(2′‐phthalimidocyclohexyloxy)acetic acid 6.

  描述了具有免疫活性的邻苯二甲酰亚胺脱壁酰肽类似物 2e-h、4c-d 和 7b 的制备。胞壁酰二肽中的 N-乙酰胞壁酸已被邻苯二甲酰化无环部分如 N-邻苯二甲酰化氨基酸 1a-c、2-（2-邻苯二甲酰亚胺乙氧基）乙酸 3 或碳环外消旋取代。反式-2-(2'-邻苯二甲酰亚胺环己氧基)乙酸 6.
• Preparation of diastereomerically pure immunologically active carbocyclic nor-muramyldipeptide analogues
  作者：Danijel Kikelj、Jurka Kidrič、Primož Pristovšek、Slavko Pečar、Uroš Urleb、Aleš Krbavčič、Helmut Hönig

  DOI：10.1016/s0040-4020(01)90182-6

  日期：1992.7

  The preparation of diastereomerically pure immunologically active carbocyclic nor-muramyldipeptide analogues (1′R,2′R)-/(1′S,2′S)-N-[2-(2′-acetylamino-cyclohexyloxy)acetyl]-L-alanyl-D-isoglutamine and (1′R,2′R)-/(1′S,2′S)-N-]2-(2′-acetylaminocyclohexyloxy)acetyl]-L-alanyl-D-glutamic acid is described. The title compounds were synthesized using two independent synthetic routes from racemic trans-2-azidocyclohexanol

  非对映体纯的具有免疫活性的碳环或-muramyldipeptide类似物（1'R，2'R）-/（1'S，2'S）-N- [2-（2'-乙酰氨基-环己氧基）乙酰基] -L的制备-丙氨酰基-D-异谷氨酰胺和（1'R，2'R）-/（1'S，2'S）-N-] 2-（2'-乙酰氨基环己氧基）乙酰基] -L-丙氨酰基-D-谷氨酸描述。使用两种独立的合成途径，分别由外消旋的反式-2-叠氮基环己醇和（1R，2R）-/（1S，2S）-2-氨基环己醇合成标题化合物。
• Immunologically active dipeptidyl saccharides and methods of preparation
  申请人：Merck & Co., Inc.

  公开号：EP0014159A1

  公开（公告）日：1980-08-06

  2-Amino-2-deoxy-glycoses of the general structural formula: wherein R1 is hydrogen, alkyl (1-7C), substituted alkyl (1-7C), phenyl, substituted phenyl, benzyl, or substituted benzyl; R2 is alkyl, substituted alkyl, phenyl, or substituted phenyl; R3 is H or lower alkyl (1-10C) with the proviso that when the aminoglycose has the 2-amino-2-deoxy-D-glucose configuration, R3 cannot be H; R4 and R5 are same or different and are H, aliphatic or aromatic acyl (2-21 C) or substituted acyl (2-21 C); R6 is H, or R6-R7 together is -CH2-CH2-CH2-, R7 is H, alkyl (1-7C), hydroxymethyl, mercaptomethyl, benzyl, or substituted benzyl; R8 and Rg each is carboxyl, esterified carboxyl (1-7C), amidated carboxyl, or mono- or di-alkyl-(1-3C)-amidated carboxyl; provided that when R3 is lower alkyl, the stereochemistry at asymmetric center I can be either D or L, but that when the caminoglycose has the 2-amino-2-deoxy-D-glucose configuration, the stereochemistry at I cannot be D; when R7 is not H, the stereochemistry at asymmetric center II is either L or D; and the stereochemistry at asymmetric center III is D. These compounds possess immunostimulatory properties.

  结构通式为 2-氨基-2-脱氧甘氨酸： 其中 R1 是氢、烷基（1-7C）、取代烷基（1-7C）、苯基、取代苯基、苄基或取代苄基； R2 是烷基、取代的烷基、苯基或取代的苯基； R3 是 H 或低级烷基（1-10C），但当氨基糖具有 2-氨基-2-脱氧-D-葡萄糖构型时，R3 不能是 H； R4 和 R5 相同或不同，并且是 H、脂肪族或芳香族酰基（2-21C）或取代酰基（2-21C）； R6 是 H，或 R6-R7 合在一起是-CH2-CH2-CH2-、 R7 是 H、烷基（1-7C）、羟甲基、巯甲基、苄基或取代的苄基； R8 和 Rg 分别是羧基、酯化羧基 (1-7C)、酰胺化羧基或单-或二-烷基-(1-3C)-酰胺化羧基； 条件是当 R3 是低级烷基时，不对称中心 I 的立体化学结构可以是 D 或 L，但当骆驼糖具有 2-氨基-2-脱氧-D-葡萄糖构型时，I 的立体化学结构不能是 D； 当 R7 不是 H 时，不对称中心 II 的立体化学结构为 L 或 D；以及 不对称中心 III 的立体化学结构为 D。 这些化合物具有免疫刺激特性。