N-(4-nitrobenzenesulfonyl)methionine methyl ester | 250697-55-3

• 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: N-(4-nitrobenzenesulfonyl)methionine methyl ester
• 英文别名: (S)-methyl 4-(methylthio)-2-(4-nitrophenylsulfonamido)butanoate；methyl (2S)-4-methylsulfanyl-2-[(4-nitrophenyl)sulfonylamino]butanoate
• CAS: 250697-55-3
• 化学式: C₁₂H₁₆N₂O₆S₂
• mdl: MFCD00758849
• 分子量: 348.401
• InChiKey: SYQKXKJIXCWEDB-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  152
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(4-nitrobenzenesulfonyl)methionine methyl ester 在 N-甲基吗啉 、 tin(ll) chloride 、 氯甲酸异丁酯 作用下， 以 乙酸乙酯 为溶剂， 反应 4.08h， 生成 methyl (2S)-4-methylsulfanyl-2-[[4-[[(2R)-2-(phenylmethoxycarbonylamino)-3-phenylmethoxycarbonylsulfanylpropanoyl]amino]phenyl]sulfonylamino]butanoate
  参考文献：
  名称：

  Different Amino Acid Replacements in CAAX-Tetrapeptide Based Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA-dipeptide can be replaced by tranexamic acid, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3-dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate anti-proliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX-tetrapeptide by 2-acylamino-5-aminobenzophenones.

  DOI：

  10.1002/(sici)1521-4184(19994)332:4<124::aid-ardp124>3.0.co;2-g
• 作为产物：
  描述：

  L-蛋氨酸甲酯盐酸盐 、 对硝基苯磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.17h， 以87%的产率得到N-(4-nitrobenzenesulfonyl)methionine methyl ester
  参考文献：
  名称：

  DBU 催化的对映选择性降解重排：一种四取代 2-Aryl-2-氨基酯的方法

  摘要：

  在此，我们报告了一种催化、易于扩展的协议，用于四取代的 α-芳基-α-氨基酸衍生物的对映选择性合成，使用由 DME 中的催化 DBU 和 Na 2 CO 3水溶液组成的双相系统。在非常温和的反应条件下，不使用金属或手性添加剂，这种多相系统促进官能化N-芳基磺酰基 α-氨基酯降解重排成相应的四取代 2-芳基-2-氨基酯，具有高对映体比（高达97.5:2.5) 和良好的产量（高达 95%）。

  DOI：

  10.1002/adsc.202100493

文献信息

• Design, synthesis and early structure–activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate
  作者：Martin Schlitzer、Markus Böhm、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1016/s0968-0896(00)00138-3

  日期：2000.8

  Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the res protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N-alpha-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and evaluation of homofarnesoyl-substituted CAAX-peptidomimetics as farnesyltransferase inhibitors and antiproliferative agents
  作者：Martin Schlitzer、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1016/s0968-0896(99)00165-0

  日期：1999.9

  Several CAAX-peptidomimetics were linked to homofarnesoic acid via a beta-alanyl spacer with the intention to obtain a novel type of bisubstrate analogue farnesyltransferase inhibitors. However, the compounds were found to be only weakly active in the farnesyltransferase inhibition assay. Nevertheless, they displayed antiproliferative activity against different tumor cell lines in the low micromolar range. Replacement of the beta-alanine moiety by aspartic acid-1-methyl ester resulted in a compound which inhibited the farnesyltransferase with an IC50 of 860 nM. The corresponding free acid showed a eightfold loss in activity (IC50 = 6.9 microM).
• Different Amino Acid Replacements in CAAX-Tetrapeptide Based Peptidomimetic Farnesyltransferase Inhibitors
  作者：Martin Schlitzer、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1002/(sici)1521-4184(19994)332:4<124::aid-ardp124>3.0.co;2-g

  日期：1999.4

  In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA-dipeptide can be replaced by tranexamic acid, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3-dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate anti-proliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX-tetrapeptide by 2-acylamino-5-aminobenzophenones.
• DBU Catalysed Enantioselective Degradative Rearrangement: a Way to Tetrasubstituted 2‐Aryl‐2‐Amino Esters
  作者：Camilla Loro、Roberto Sala、Michele Penso、Francesca Foschi

  DOI：10.1002/adsc.202100493

  日期：2021.8.13

  Na2CO3. Under very mild reaction conditions, without using metal or chiral additives, this heterogeneous system promotes the degradative rearrangement of functionalized N-aryl sulphonyl α-amino esters into the corresponding tetrasubstituted 2-aryl-2-amino esters, with high enantiomeric ratios (up to 97.5:2.5) and good yields (up to 95%).

  在此，我们报告了一种催化、易于扩展的协议，用于四取代的 α-芳基-α-氨基酸衍生物的对映选择性合成，使用由 DME 中的催化 DBU 和 Na 2 CO 3水溶液组成的双相系统。在非常温和的反应条件下，不使用金属或手性添加剂，这种多相系统促进官能化N-芳基磺酰基 α-氨基酯降解重排成相应的四取代 2-芳基-2-氨基酯，具有高对映体比（高达97.5:2.5) 和良好的产量（高达 95%）。