Boc-Phe-NH-Ada | 80110-59-4

• 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: Boc-Phe-NH-Ada
• 英文别名: tert-butyl (1-((adamantan-1-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate；tert-butyl N-[(1S)-1-[(adamantan-1-yl)carbamoyl]-2-phenylethyl]carbamate；tert-butyl N-[(2S)-1-(1-adamantylamino)-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 80110-59-4
• 化学式: C₂₄H₃₄N₂O₃
• 分子量: 398.546
• InChiKey: ALNVPGDHLFEFFS-WNZYQOIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Boc-Phe-NH-Ada 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 (S)-2-[(S)-1-(Adamantan-1-ylcarbamoyl)-2-phenyl-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties

  摘要：

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.

  DOI：

  10.1021/jm030649p
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 6.33h， 生成 Boc-Phe-NH-Ada
  参考文献：
  名称：

  伯-仲二胺催化的α，β-不饱和酮的高度对映选择性环氧化

  摘要：

  α，β-不饱和酮的不对称环氧化已通过使用功能性且易于获得的伯-仲二胺作为催化剂来实现，从而以有用的收率和高对映选择性（高达99％ee）提供了有用的烷基环氧产物。

  DOI：

  10.1002/adsc.201100230

文献信息

• Studies on analgesic oligopeptides. V. Structure-activity relationship of tripeptide alkylamides, Tyr-D-Arg-Phe-X.
  作者：KENJI SUZUKI、HIROKI FUJITA、YUSUKE SASAKI、MIKI SHIRATORI、SHINOBU SAKURADA、KENSUKE KISARA

  DOI：10.1248/cpb.36.4834

  日期：——

  Twenty-one analogs based on the structure Tyr-D-Arg-Phe-X (X=OH, alkyl ester, alkylamide or amino acid having a different carbon chain) were synthesized by the solution method and their analgesic activities were tested after subcutaneous (s. c.) administration in mice. Most tripeptide alkylamides showed no analgesia at a dose of 10 mg/kg, s. c. However, some tripeptide alkylamides having the hydroxyl group on the alkyl moiety showed greater activity than morphine. Introduction of the carboxyl group on the alkyl moiety also led to tetrapeptide analogs with potent analgesia, e. g., the compound with X=β-alanine is 33 times more potent than morphine on a molar basis. These results suggest that proper carbon chain lengths and the presence of an oxygen atom at the fourth position are important for high analgesic activity in the series of D-Arg2-dermorphin analogs.

  通过溶液法合成了基于结构Tyr-D-Arg-Phe-X（X=OH，烷基酯，烷基酰胺或具有不同碳链的氨基酸）的21种类似物，并在小鼠皮下（s.c.）给药后测试了它们的镇痛活性。大多数三肽烷基酰胺在10 mg/kg，s.c.剂量下没有镇痛作用。然而，一些在烷基部分具有羟基的三肽烷基酰胺显示出比吗啡更大的活性。在烷基部分引入羧基也导致具有强效镇痛作用的四肽类似物，例如，X=β-丙氨酸的化合物在摩尔基础上比吗啡强33倍。这些结果表明，适当的碳链长度和在第四位存在氧原子对于D-Arg2-dermorphin类似物系列中的高镇痛活性是重要的。
• Organocatalytic asymmetric Michael addition of aldehydes and ketones to nitroalkenes catalyzed by adamantoyl <scp>l</scp>-prolinamide
  作者：Yongchao Wang、Dong Li、Jun Lin、Kun Wei

  DOI：10.1039/c4ra11214h

  日期：——

  series of adamantoyl L-prolinamides have been synthesized. These compounds have been found to be highly efficient organocatalysts for the Michael addition of aldehydes and ketones to nitroalkenes. Under the optimized reaction conditions, the corresponding Michael adducts were obtained in good yields (up to 95%), excellent enantioselectivities (up to 99% ee) and moderate diastereoselectivities.

  已经合成了一系列的金刚烷基L-脯氨酰胺。已经发现这些化合物是用于将醛和酮迈克尔加成至硝基烯烃的高效有机催化剂。在优化的反应条件下，以高收率（最高95％），优异的对映选择性（最高99％ee）和中等非对映选择性获得了相应的迈克尔加合物。
• Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of<i>Staphylococcus aureus</i>Sortase A
  作者：Fabian Barthels、Gabriella Marincola、Tessa Marciniak、Matthias Konhäuser、Stefan Hammerschmidt、Jan Bierlmeier、Ute Distler、Peter R. Wich、Stefan Tenzer、Dirk Schwarzer、Wilma Ziebuhr、Tanja Schirmeister

  DOI：10.1002/cmdc.201900687

  日期：2020.5.19

  community-acquired infections, with drug-resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active-site cysteine. A broad series of derivatives were synthesized to

  金黄色葡萄球菌是医院和社区获得性感染的最常见原因之一，耐药菌株每年导致数万人死亡。金黄色葡萄球菌分选酶 A 抑制剂旨在干扰毒力决定因素。我们已经确定二硫烷基苯甲酰胺是一类新型有效的分选酶 A 抑制剂，通过活性位点半胱氨酸的共价修饰发挥作用。合成了一系列广泛的衍生物来推导构效关系（SAR）。体外和计算机方法使实验观察到的结合亲和力和选择性合理化。研究发现，最活跃的化合物具有个位数的微摩尔 Ki 值，在 10 μM 的有效抑制剂浓度下，金黄色葡萄球菌纤维蛋白原附着量减少高达 66%。这种新分子类别表现出最小的细胞毒性、较低的细菌生长抑制和分选酶介导的金黄色葡萄球菌细胞粘附受损。
• SUZUKI, KENJI;FUJITA, HIROKI;SASAKI, YUSUKE;SHIRATORI, MIKI;SAKURADA, SHI+, CHEM. AND PHARM. BULL., 36,(1988) N2, C. 4834-4840
  作者：SUZUKI, KENJI、FUJITA, HIROKI、SASAKI, YUSUKE、SHIRATORI, MIKI、SAKURADA, SHI+

  DOI：——

  日期：——
• US4273704A
  申请人：——

  公开号：US4273704A

  公开（公告）日：1981-06-16