(S)-methyl 2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylate | 1186668-56-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-methyl 2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylate
• 英文别名: (S)-methyl 2-((tert-butoxycarbonyl)(phenyl)methyl)acrylate；methyl (S)-2-{[(tert-butoxycarbonyl)amino](phenyl)methyl}acrylate；methyl 2-[(S)-[(2-methylpropan-2-yl)oxycarbonylamino]-phenylmethyl]prop-2-enoate
• CAS: 1186668-56-3
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: FLCUVRIQFPYHHN-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  (S)-methyl 2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以87%的产率得到(S)-2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylic acid
  参考文献：
  名称：

  A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)

  摘要：

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.

  DOI：

  10.1021/jm300664y
• 作为产物：
  描述：

  methyl 2-[(S)-{[(R)-1-(4-methoxyphenyl)ethyl]amino}(phenyl)methyl]acrylate 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 10.0h， 生成 (S)-methyl 2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylate
  参考文献：
  名称：

  金鸡纳生物碱介导的对映体纯 3-氨基-2-亚甲基链烷酸酯（氮杂-森田-贝利斯-希尔曼加合物）的合成

  摘要：

  3-取代的 (Z)-2-(溴甲基) 丙烯酸酯在化学计量的奎尼丁存在下与 (S)-1-(4-甲氧基苯基) 乙胺反应生成 (R)-3-[(叔丁氧基羰基) 氨基]-2-亚甲基链烷酸酯（aza-Morita-Baylis-Hillman 加合物）呈对映异构纯形式。

  DOI：

  10.1002/ejoc.201101244

文献信息

• Organocatalytic Enantioselective Mannich-Type Reaction of Phosphorus Ylides:  Synthesis of Chiral <i>N</i>-Boc-β-Amino-α-methylene Carboxylic Esters
  作者：Yan Zhang、Yan-Kai Liu、Tai-Ran Kang、Ze-Kai Hu、Ying-Chun Chen

  DOI：10.1021/ja7114844

  日期：2008.2.1

  The first asymmetric Mannich-type reaction of stabilized phosphorus ylides and N-Boc aldimines was described promoted by a readily available and recyclable chiral bisthiourea organocatalyst. Subsequent reaction with formalin smoothly provides N-Boc-β-amino-α-methylene carboxylic esters in a highly enantiomerically enriched form (up to 96% ee).

  稳定的磷叶立德和 N-Boc 醛亚胺的第一个不对称曼尼希型反应由易于获得且可回收的手性双硫脲有机催化剂促进。随后与福尔马林的反应顺利地提供了高度对映体富集形式（高达 96% ee）的 N-Boc-β-氨基-α-亚甲基羧酸酯。
• Catalytic Asymmetric Mannich Reactions of Sulfonylacetates
  作者：Carlo Cassani、Luca Bernardi、Francesco Fini、Alfredo Ricci

  DOI：10.1002/anie.200900701

  日期：2009.7.20

  synthetic equivalents of a variety of α‐carboxylate anions. Phase‐transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from α‐amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of β‐amino acid derivatives.

  砜与砜：芳基磺酰乙酸盐可以看成是各种α-羧酸根阴离子的合成等价物。相转移催化（PTC）使它们能够轻度去质子化，并催化不对称添加到α-酰胺基砜现场生成的高反应性亚胺上（见方案； Pg =保护基）。通过将其直接转化为一系列β-氨基酸衍生物，证明了该产品的合成效用。
• Lewis-Base-Catalyzed <i>N</i>-Allylation of Silyl Carbamate Latent Pronucleophiles with Allylic Fluorides
  作者：Markus Lange、F. Lorenz Meyer、Olena Nosovska、Ivan Vilotijevic

  DOI：10.1021/acs.orglett.3c03228

  日期：2023.12.29

  Lewis base catalysts. The reactions are rendered enantioselective in the presence of chiral Lewis base catalysts and produce suitably protected derivatives of enantioenriched chiral β-amino acids. The design of the latent pronucleophile featuring both a silyl group and an electron-deficient carbamate is instrumental in lowering the nucleophilicity of nitrogen and enabling enantioselective allylation

  氨基甲酸甲硅烷基酯是氨基甲酸酯的潜在亲核试剂替代物，在常见的路易斯碱催化剂存在下，使用烯丙基氟化物进行烯丙基化。该反应在手性路易斯碱催化剂存在下具有对映选择性，并产生对映体富集的手性 β-氨基酸的适当保护的衍生物。具有甲硅烷基和缺电子氨基甲酸酯的潜在亲核试剂的设计有助于降低氮的亲核性并在手性金鸡纳生物碱催化剂存在下实现对映选择性烯丙基化。
• Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent μ-Opioid Agonists
  作者：Xin Liu、Yuan Wang、Yanhong Xing、Jing Yu、Hong Ji、Ming Kai、Zilong Wang、Dan Wang、Yixin Zhang、Depeng Zhao、Rui Wang

  DOI：10.1021/jm400195y

  日期：2013.4.11

  Recently we reported the synthesis and structure activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-beta Pro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-beta Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (K-i(mu) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, E-max = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.