L-leucyl-L-valine methyl ester trifluoroacetate | 82176-06-5

• 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: L-leucyl-L-valine methyl ester trifluoroacetate
• 英文别名: methyl (2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoate;2,2,2-trifluoroacetic acid
• CAS: 82176-06-5
• 化学式: C₂HF₃O₂*C₁₂H₂₄N₂O₃
• 分子量: 358.358
• InChiKey: ZZVQTBALYGBDKO-IYPAPVHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  118.72
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  、 L-leucyl-L-valine methyl ester trifluoroacetate 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 silver(I) acetate 、 palladium diacetate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成
  参考文献：
  名称：

  Site-Selective C(sp³)–H Functionalization of Di-, Tri-, and Tetrapeptides at the N-Terminus

  摘要：

  Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp(3))-H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp(3))-H activation toward postsynthetic modification of a broader range of peptides.

  DOI：

  10.1021/ja510233h
• 作为产物：
  描述：

  4-硝基苯基 N-(叔丁氧羰基)-L-亮氨酸酯 在 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 L-leucyl-L-valine methyl ester trifluoroacetate
  参考文献：
  名称：

  Kolomeitseva, L. A.; Kocharova, N. A.; Ibragimova, L. D., Journal of general chemistry of the USSR, 1982, vol. 52, # 2, p. 372 - 377

  摘要：

  DOI：

文献信息

• Synthesis and Host−Guest Studies of Chiral <i>N</i>-Linked Peptidoresorc[4]arenes
  作者：Bruno Botta、Ilaria D'Acquarica、Giuliano Delle Monache、Deborah Subissati、Gloria Uccello-Barretta、Massimo Mastrini、Samuele Nazzi、Maurizio Speranza

  DOI：10.1021/jo7016636

  日期：2007.11.1

  (10, 11, ent-10, and ent-11) tetrafunctionalized at the feet with valyl-leucine [ll- (6); dd- (ent-6)] and leucyl-valine [ll- (9); dd- (ent-9)] methyl esters have been synthesized. These compounds, obtained by conjugation of macrocycle tetracarboxylic acid chlorides with the appropriate terminal amino groups of the above dipeptides, are N-linked peptidoresorc[4]arenes. We found that these macrocycles

  四个锥体resorc [4]芳烃八甲基醚（10，11，耳鼻喉科- 10，和ENT - 11）在与缬氨酰基-亮氨酸[脚tetrafunctionalized LL - （6）; dd-（eNT - 6）]和亮氨酰缬氨酸[ ll-（9）; dd-（eNT - 9）]甲酯已经合成。通过使大环四羧酸氯化物与上述二肽的适当末端氨基缀合而获得的这些化合物是N连接的肽间苯二酚[4]芳烃。我们发现这些大环化合物（M）通过形成相对稳定的宿主-客体复合物（[M·G]），能够抵抗色谱纯化，从而在溶液和气相中均能够将同系物二肽识别为客体（G）。但不要加热。通过NMR方法（包括NMR DOSY实验）研究了溶液中M和G之间的络合现象，以检测平移扩散。通过Foster-Fyfe方法获得的配合物[ 10 · 6 ]和[ 10 · eNT - 6的杂合常数为2030和186 M -1分别与二肽本身的自缔合常数相当。相反，通
• Lead Optimization of 2-Phenylindolylglyoxylyldipeptide Murine Double Minute (MDM)2/Translocator Protein (TSPO) Dual Inhibitors for the Treatment of Gliomas
  作者：Simona Daniele、Valeria La Pietra、Elisabetta Barresi、Salvatore Di Maro、Eleonora Da Pozzo、Marco Robello、Concettina La Motta、Sandro Cosconati、Sabrina Taliani、Luciana Marinelli、Ettore Novellino、Claudia Martini、Federico Da Settimo

  DOI：10.1021/acs.jmedchem.5b01767

  日期：2016.5.26

  In glioblastoma multiforme (GBM), translocator protein (TSPO) and murine double minute (MDM)2/p53 complex represent two druggable targets. We recently reported the first dual binder 3 possessing a higher anticancer effect in GBM cells than the standards PK11195 1 or Nutlin-3 2 singularly applied. Herein, through a structure activity relationship study, we developed derivatives 4-10 with improved potencies toward both TSPO and MDM2. As a result, compound 9: (i) reactivated the p53 functionality; (ii) inhibited the viability of two human GBM cells; (iii) impaired the proliferation of glioma cancer stem cells (CSCs), more resistant to chemotherapeutics and responsible of GBM recurrence; (iv) sensitized GBM cells and CSCs to the activity of temozolomide; (v) directed its effects preferentially toward tumor cells with respect to healthy ones. Thus, 9 may represent a promising cytotoxic agent, which is worthy of being further developed for a therapeutic approach against GBM, where the downstream p53 signaling is intact and TSPO is overexpressed.
• KONG, KANGHOU;LIN, YONGCHENG, CHZHUNSHAN DASYUEH SYUEHBAO/TSZYZHAN KEHSYUEHBAN,(1988) N 4, S. 55-62
  作者：KONG, KANGHOU、LIN, YONGCHENG

  DOI：——

  日期：——