(2S,3s)-3-氨基-2-羟基-4-苯基丁酸 | 62023-59-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2S,3s)-3-氨基-2-羟基-4-苯基丁酸
• 英文名称: (2S,3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoic acid
• 英文别名: (2 S ,3 S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutyric acid；(2S,3S)-N-(benzyloxycarbonyl)-3-amino-2-hydroxy-4-phenylbutanoic acid；(2S,3S)-3-(Z-amino)-2-hydroxy-4-phenylbutyric acid；(2S,3S)-2-hydroxy-4-phenyl-3-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 62023-59-0
• 化学式: C₁₈H₁₉NO₅
• 分子量: 329.353
• InChiKey: JXJYTERRLRAUSF-HOTGVXAUSA-N

物化性质

• 沸点：
  581.9±50.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3s)-3-氨基-2-羟基-4-苯基丁酸 在 钯 氢气 作用下， 生成 (2S,3s)-3-氨基-2-羟基-4-苯基丁酸
  参考文献：
  名称：

  Synthesis and structure-activity relations of bestatin analogs, inhibitors of aminopeptidase B

  摘要：

  Stereoisomers and analogues of bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, were synthesized and tested for aminopeptidase B and leucine aminopeptidase inhibiting activity. Among the eight stereoisomers, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the L-leucine residue of bestatin was substituted with other amino acids, only the one containing isoleucine showed more activity than bestatin. Norleucine, norvaline, methionine, valine, serine, glutamine, phenylalanine, glutamic acid, proline, and lysine analogues gave, in that order, decreasing activity. Alkyl and phenyl sub stitution for the benzyl group of bestatin decreased the activity markedly. p-Methyl-, p-chloro-, and p-nitrobestatins showed greater activity than bestatin.

  DOI：

  10.1021/jm00214a010
• 作为产物：
  描述：

  苄基(S)-1-(N-甲氧基-N-甲基氨基甲酰基)-2-苯乙基氨基甲酸酯 在 lithium hydroxide 、 sodium tetrahydroborate 、 叔丁基锂 、 臭氧 、 magnesium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.83h， 生成 (2S,3s)-3-氨基-2-羟基-4-苯基丁酸
  参考文献：
  名称：

  Selectivity in the Inhibition of HIV and FIV Protease: Inhibitory and Mechanistic Studies of Pyrrolidine-Containing .alpha.-Keto Amide and Hydroxyethylamine Core Structures

  摘要：

  This paper describes the development of new pyrrolidine-containing alpha-keto amide and hydroxyethylamine core structures as mechanism based inhibitors of the HIV and FIV proteases. It was found that the alpha-keto amide core structure 2 is approximately 300-fold better than the corresponding hydroxyethylamine isosteric structure and 1300-fold better than the corresponding phosphinic acid derivative as an inhibitor of the HIV protease. The alpha-keto amide is however not hydrated until it is bound to the HIV protease as indicated by the NMR study and the X-ray structural analysis. Further analysis of the inhibition activities of hydroxyethylamine isosteres containing modified pyrrolidine derivatives revealed that a cis-methoxy group at C-4 of the pyrrolidine would improve the binding 5-and 25-fold for the trans-isomer. When this strategy was applied to the alpha-keto amide isostere, a cis-benzyl ether at C-4 was found to enhance binding 3-fold. Of the core structures prepared as inhibitors of the HIV protease, none show significant inhibitory activity against the mechanistically identical FIV protease, and additional complementary groups are needed to improve inhibition.

  DOI：

  10.1021/ja00153a008

文献信息

• HIV protease inhibitors
  申请人：Wong Chi-Huey

  公开号：US06900238B1

  公开（公告）日：2005-05-31

  Combinatorial libraries of HIV and FIV protease inhibitors are characterized by α-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

  HIV和FIV蛋白酶抑制剂的组合库以α-酮酰胺或羟乙基胺核心结构为特征，一侧为取代吡咯烷、哌啶或氮代糖，另一侧为苯丙氨酸、酪氨酸或取代酪氨酸。这些库是通过一步偶联反应合成的。通过筛选这些库，识别出对HIV和FIV蛋白酶的结合和抑制活性高效的药物候选化合物。对HIV和FIV蛋白酶都显示出临床有用活性的药物候选化合物被确定为潜在对抗由于HIV耐药株的发展而导致的抑制活性丧失。
• Syntheses of HIV Protease Inhibitors Having a Peptide Moiety Which.
  作者：Akira ASAGARASU、Taketo UCHIYAMA、Kazuo ACHIWA

  DOI：10.1248/cpb.46.697

  日期：——

  Some HIV-protease inhibitor derivatives having an N-carbomethoxycarbonyl-prolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120 were designed and synthesized. Almost all the compounds bearing CPF on the phenoxyacetyl group showed protease-inhibitory activity. Compounds 25a and 25b, which have the CPF moiety at the ortho- and meta-positions of the phenoxyacetyl group, respectively, had anti-HIV activity, although the others showed only protease-inhibitory activity. These results suggest that 25b binds to gp120 and inhibits HIV protease.

  设计并合成了一些含有N-羧甲氧羰基-脯氨酰-苯丙氨酸苄酯（CPF）部分作为gp120结合位点的HIV蛋白酶抑制剂衍生物。几乎所有在苯氧乙酰基上带有CPF的化合物都显示出蛋白酶抑制活性。化合物25a和25b分别在苯氧乙酰基的邻位和对位上具有CPF部分，它们具有抗HIV活性，尽管其他化合物仅显示出蛋白酶抑制活性。这些结果表明25b能与gp120结合并抑制HIV蛋白酶。
• Synthesis of Dipeptide-Type Human Immunodeficiency Virus (HIV) Protease Inhibitors with a Binding Unit to GP120.
  作者：Akira ASAGARASU、Nao TAKAYANAGI、Kazuo ACHIWA

  DOI：10.1248/cpb.46.867

  日期：——

  Some dipeptide-type human immunodeficiency virus (HIV) protease inhibitors derived from KNI-102, with a N-carbomethoxycarbonylprolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120, were synthesized. Compounds 11a showed 7-100 times higher HIV protease-inhibitory activity (11a; IC50=0.90 μg/ml, 1.1 μM) than the standard compound 3 or 4 (3; IC50=3.7 μg/ml, 7.7 μM, 4; IC50=75 μg/ml, 155 μM). Generally, the compounds substituted at the o-position of the phenoxyacetyl group 7a, 11a, 16a and 12a showed several times higher inhibitory activity than 3.

  一些来源于KNI-102的二肽类人免疫缺陷病毒（HIV）蛋白酶抑制剂被合成，这些抑制剂具有N-羧甲氧基碳酰脯氨酸-苯丙氨酸苄基酯（CPF）基团作为与gp120结合的位点。化合物11a的HIV蛋白酶抑制活性比标准化合物3或4高出7-100倍（11a；IC50=0.90 μg/ml，1.1 μM；3；IC50=3.7 μg/ml，7.7 μM；4；IC50=75 μg/ml，155 μM）。一般来说，在苯氧乙酰基团o位取代的化合物7a、11a、16a和12a显示出的抑制活性比3高出几倍。
• Synthesis and Human Immunodeficiency Virus(HIV)-1 protease Inhibitory Activity of Tripeptide Analogues Containing a Dioxoethylene Moiety.
  作者：Tomoyuki KITAZAKI、Tsuneo ASANO、Koichi KATO、Shoji KISHIMOTO、Katsumi ITOH

  DOI：10.1248/cpb.42.2636

  日期：——

  Tripeptide analogues 2 and 3 containing a dioxoethylene moiety were designed based on the characteristic structure of the naturally occurring human immunodeficiency virus (HIV)-1 protease inhibitors RPI-856 A, B, C and D (1). The compounds (2, 3) prepared showed high inhibitory activity, comparable to that of RPI-856 A, against HIV-1 protease in vitro.

  根据天然存在的人类免疫缺陷病毒（HIV）-1 蛋白酶抑制剂 RPI-856 A、B、C 和 D (1)的特征结构，设计了含有二氧乙烯分子的三肽类似物 2 和 3。所制备的化合物（2、3）在体外对 HIV-1 蛋白酶具有很高的抑制活性，与 RPI-856 A 相当。
• Synthesis of a cis-conformationally restricted peptide bond isostere and its application to the inhibition of the HIV-1 protease
  作者：Andrew D. Abell、Glenn J. Foulds

  DOI：10.1039/a702458d

  日期：——

  A synthesis of a new, tetrazole-based, cis-constrained hydroxyethylamine peptide bond isostere is reported. This has been used to produce a new class of HIV-1 protease inhibitor.

  报告了一种新的、基于四氮唑的顺式受约束羟乙基胺肽键异构体的合成。该化合物已被用于生产一种新型的 HIV-1 蛋白酶抑制剂。