Boc-L-苯丙氨酸-2-溴乙酯 | 221351-21-9

• 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: Boc-L-苯丙氨酸-2-溴乙酯
• 英文名称: Boc-L-phenylalanine-2-bromoethyl ester
• 英文别名: 2-bromoethyl (tert-butoxycarbonyl)-L-phenylalaninate；2-bromoethyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate
• CAS: 221351-21-9
• 化学式: C₁₆H₂₂BrNO₄
• 分子量: 372.259
• InChiKey: RWYMWTCFRODTFE-ZDUSSCGKSA-N

物化性质

• 沸点：
  471.8±40.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-L-苯丙氨酸-2-溴乙酯 在 N,N'-二环己基-4-吗啉脒 、 盐酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-Amino-3-phenyl-propionic acid 2-{[2-((S)-2-amino-3-phenyl-propionyloxy)-ethoxy]-[2-(6-amino-purin-9-yl)-ethoxymethyl]-phosphinoyloxy}-ethyl ester
  参考文献：
  名称：

  9- [2-（膦酰基甲氧基）乙基]腺嘌呤（PMEA）的新型双（L-氨基酸）酯前药的设计与合成，具有改善的抗HBV活性。

  摘要：

  合成了一系列新型的9- [2-（膦酰基甲氧基）乙基]腺嘌呤（PMEA）双（L-氨基酸）酯前药，并在HepG 2 2.2.15细胞中评估了它们的抗HBV活性。与用作阳性对照的阿德福韦酯相比，化合物11、12、21、22、26和27表现出更强的抗HBV活性和更高的选择性指数（SI）。被发现是最有效的化合物11，其效力是阿德福韦酯的5倍，EC50值为0.095 microM，CC50值为6636 microM。化合物11的SI值（> 69,000）分别比阿德福韦酯和拉米夫定高60倍和24倍。体外稳定性研究表明，化合物11比阿德福韦酯更稳定，t1 / 2为270分钟。

  DOI：

  10.1016/j.bmcl.2006.10.021
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 2-溴乙醇 在 4-二甲氨基吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 Boc-L-苯丙氨酸-2-溴乙酯
  参考文献：
  名称：

  新的双（1-氨基酸）酯替诺福韦前药的设计，合成和抗HBV活性。

  摘要：

  设计并合成了一系列替诺福韦（TFV）的双（1-氨基酸）酯前药，作为这项工作中的新型抗HBV药物。四种化合物11、12a，12d和13b表现出比母体药物TFV更好的抗HBV活性（IC 50：0.71-4.22μM）。发现活性最高的化合物11（IC 50：0.71μM）是TFV的双（1-缬氨酸）酯前药，其富马酸替诺福韦酯（TDF）的AUC 0–∞，C max和F％明显更高，体内有力 在鸭HBV（DHBV）模型和HBV DNA流体动力学小鼠模型中疗效不亚于TDF，并且它可以作为进一步发现抗HBV药物的有前途的先导化合物。

  DOI：

  10.1021/acsmedchemlett.9b00184

文献信息

• [EN] PRODRUGS OF KALLIKREIN INHIBITORS<br/>[FR] PROMÉDICAMENTS D'INHIBITEURS DE LA KALLICRÉINE
  申请人：BIOCRYST PHARM INC

  公开号：WO2018081513A1

  公开（公告）日：2018-05-03

  Disclosed are compounds of formula I, II, and III, and pharmaceutically acceptable salts thereof, which are inhibitors of kallikrein. Also provided are pharmaceutical compositions comprising such a compound, and methods involving use of the compounds and compositions in the treatment and prevention of acquired or hereditary angioedema, or other diseases and conditions characterized by aberrant kallikrein activity. (I) (II) (III)

  公开了式I、II和III的化合物及其药学上可接受的盐，它们是激肽释放酶抑制剂。还提供了包含此类化合物的药物组合物，以及使用这些化合物和组合物治疗和预防获得性或遗传性血管性水肿或其他以异常激肽释放酶活性为特征的疾病和病症的方法。(I) (II) (III)
• Design, synthesis and in vitro evaluation of mono (2, 2, 2-trifluoroethyl) esters, mono l-amino acid ester prodrugs of acyclic nucleoside phosphonates as anti-HBV agents
  作者：Xiao Zhong Fu、Yu Ou、Jan Xin、Yu She Yang

  DOI：10.1016/j.cclet.2011.09.005

  日期：2011.12

  Abstract A series of novel mono (2, 2, 2-trifluoroethyl) esters, mono l -amino acid ester prodrugs of acyclic nucleoside phosphonates was synthesized and their in vitro anti-HBVactivity was evaluated in HepG 2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil and alamifovir (MCC-478) with EC 50 and CC 50 values of 0.01 μmol/L and

  摘要合成了一系列新型的无环核苷膦酸酯单（2，2，2-三氟乙基）酯，单1-氨基酸酯前药，并在HepG 2 2.2.15细胞中评估了它们的体外抗HBV活性。与阿德福韦酯和阿拉米福韦（MCC-478）相比，化合物1d表现出更强的抗HBV活性和较低的细胞毒性，EC 50和CC 50值分别为0.01μmol/ L和> 8000μmol/ L。
• Access to Polysulfides through Photocatalyzed Dithiosulfonylation
  作者：Xiaorui Ren、Qiumin Ke、Yuanyuan Zhou、Jingchao Jiao、Guoxin Li、Si Cao、Xuyong Wang、Qianwen Gao、Xi Wang

  DOI：10.1002/anie.202302199

  日期：2023.6.19

  of alkenes, alkynes, 1,3-enynes, and [1.1.1]propellane with dithiosulfonates. The resulting dithiosulfonylated styrene is an excellent nucleophilic disulfuration reagent, which can react with a variety of electrophiles to access unsymmetric disulfides efficiently.

  在此，我们报告了烯烃、炔烃、1,3-烯炔和 [1.1.1] 丙烷与二硫代磺酸盐的一般光催化双功能化。所得二硫代磺酰化苯乙烯是一种优良的亲核二硫化试剂，可与多种亲电试剂反应，有效地获得不对称二硫化物。
• Synthesis, anti-HBV activity and renal cell toxicity evaluation of mixed phosphonate prodrugs of adefovir
  作者：Xiao-Zhong Fu、Yu Ou、Jian-Ying Pei、Ying Liu、Jing Li、Wen Zhou、Yan-Yu Lan、Ai-Min Wang、Yong-Lin Wang

  DOI：10.1016/j.ejmech.2012.01.013

  日期：2012.3

  A series of phosphonate ester prodrugs of adefovir incorporating L-amino (thio)acid and non-steroidal anti-inflammatory drug (NSAID) moieties were synthesized and their anti-HBV activity and renal cell toxicity were evaluated in HepG2 2.2.15 and HK-2 cells respectively. Bioactivity evaluation results revealed that this kind of adefovir prodrug have lower renal cell toxicity than adefovir dipivoxil. Compounds 8a and 8b, incorporating the NSAID ketoprofen and the L-amino acid (Val or Ile) structural fragments, exhibited more potent anti-HBV activity than adefovir dipivoxil with IC50 = 0.51 and 0.73 mu M, SI = 1697.64 and 881.92 respectively. In vitro stability studies showed that the synthesized prodrugs have higher chemical and plasma stability than the positive control adefovir dipivoxil. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Chemoenzymatic Synthesis of Nucleopeptides
  作者：Stefanie Flohr、Volker Jungmann、Herbert Waldmann

  DOI：10.1002/(sici)1521-3765(19990201)5:2<669::aid-chem669>3.0.co;2-v

  日期：1999.2.1

  Nucleoproteins, in which the hydroxy group of a serine, a threonine, or a tyrosine, is linked through a phosphodiester group to the 3'- or 5'-end of DNA or RNA, play decisive roles in important biological processes. They may even have a major part in the process of viral replication by nucleoprotein-primed elongation of the oligonucleotide strand. For the study of the biological phenomena, in which nucleoproteins are involved, nucleopeptides with the characteristic linkage between the peptide chain and the oligonucleotide of their parent nucleoproteins may serve as powerful tools. However, the synthesis of these compounds is complicated by their pronounced acid- and base-lability, as well as their multifunctionality. As a result, protecting groups, which can be removed under the mildest conditions, are required. For the construction of such peptide conjugates using a flexible building block strategy, a combination of enzyme-labile and chemical protecting groups was developed. The C-terminal blocking function can be removed selectively from fully protected nucleoamino acid methyl, 2-methoxyethyl (ME), and methoxyethoxyethyl (MEE) esters by saponification of the esters. After elongation of the peptide chain with amino acid or peptide methyl, ME, MEE, and choline esters, the C-terminal ester blocking group can again be removed easily. The methyl, ME, and MEE esters are cleaved off with lipase, and the choline ester group is selectively attacked by butyrylcholine esterase. The nucleoamino acids and peptides formed may be fully deprotected. To this end, the enzyme-labile N-phenylacetyl (PhAc) group, which was employed to mask the amino functions of the nucleobases, was removed. The O-acetate in the deoxyribose was saponified, and the allyl protecting groups present were cleaved by Pd-0-mediated allyl transfer. By combination of these techniques, a nucleopeptide was produced, which represents the characteristic linkage region of the nucleoprotein of adenovions 2. The conditions, under which the enzymatic deprotections proceed, are so mild that no undesired side reaction is observed, that is no depurination or beta elimination of the nucleosides occurs. In addition, the specificity of the biocatalysts ensures that the peptide bonds and the other protecting groups present are not attacked either.