toluene-4-sulfonic acid (S)-2-tert-butoxycarbonylamino-4-methyl-pentyl ester | 112157-30-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: toluene-4-sulfonic acid (S)-2-tert-butoxycarbonylamino-4-methyl-pentyl ester
• 英文别名: [(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl] 4-methylbenzenesulfonate
• CAS: 112157-30-9
• 化学式: C₁₈H₂₉NO₅S
• 分子量: 371.498
• InChiKey: XSWFZMUVWLFYHT-HNNXBMFYSA-N

物化性质

• 沸点：
  496.4±28.0 °C(Predicted)
• 密度：
  1.118±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  toluene-4-sulfonic acid (S)-2-tert-butoxycarbonylamino-4-methyl-pentyl ester 在 盐酸 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 (S)-3-(benzyloxycarbonylamino)-5-methylhexanoic acid
  参考文献：
  名称：

  Chemoenzymatic Synthesis of 4-Amino-2-hydroxy Acids:  A Comparison of Mutant and Wild-Type Oxidoreductases

  摘要：

  We describe a new chemoenzymatic synthesis of enantiopure 4-amino-2-hydroxy acids using two biotransformations in a single-pot process in aqueous medium. These compounds are valuable as gamma-turn mimics for investigations into the secondary structure of peptides. The enzyme substrates are a series of carbobenzyloxy (CBZ)-protected 4-amino-2-keto esters, prepared efficiently from the L-amino acids, alanine, leucine, phenylalanine, and valine. First, the alpha-amino acids were converted to the corresponding beta-amino acids in a simple five-step procedure. A further one-carbon homologation via ozonolysis of the corresponding beta-keto cyanophosphoranes gave the required alpha-keto esters in good yield. The enzyme catalyzed hydrolyses of all the alpha-keto esters to the corresponding alpha-keto acids proceeded smoothly with the lipase from Candida rugosa. Using the same reaction pot, it was found that wild-type lactate dehydrogenases from either Bacillus stearothermophilus (BS-LDH) or Staphylococcus epidermidis (SE-LDH) could be used to specifically reduce the ketone of the alanine-derived alpha-keto acid 2, giving the (S)- and (R)-2-hydroxy acids, respectively, in good yields. However, the more bulky alpha-keto acids 3, 4, and 5 (derived from valine, leucine, and phenylalanine) were not substrates for these enzymes. In contrast, the genetically engineered H205Q mutant of D-hydroxyisocaproate dehydrogenase proved to be an ideal catalyst for the reduction of all the alpha-keto acids 2-5, giving excellent yields of the CBZ-protected (2R,4S)-4-amino-2-hydroxy acids as single diastereomers. This genetically engineered oxidoreductase has great potential value in synthesis due to its broad substrate specificity and high catalytic activity. For example, reduction of 1 mmol of N-protected (S)-4-amino-2-oxopentanoic acid 2 took just 4 h with the H205Q mutant giving, after esterification, the (R)-2-alcohol 25 in 85% yield, whereas with SE-LDH the reaction required 4 days to give a 67% yield of 25.

  DOI：

  10.1021/jo980821a
• 作为产物：
  描述：

  L-亮氨醇 在 吡啶 、 氢氧化钾 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 toluene-4-sulfonic acid (S)-2-tert-butoxycarbonylamino-4-methyl-pentyl ester
  参考文献：
  名称：

  Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation

  摘要：

  Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH, CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most efficient with IC50's in the 11-50 nM range. These results suggest that the S1 subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting side chains of moderate bulk endowed with some degree of freedom. The iv administration of the inhibitors, alone, did not induce antinociceptive responses on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the disulfides of methioninethiol [H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors capable of crossing the blood-brain barrier.

  DOI：

  10.1021/jm00085a013

文献信息

• Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents
  作者：Liyu Zhao、Linfeng Tian、Nannan Sun、Yin Sun、Yixuan Chen、Xinran Wang、Shizhen Zhao、Xin Su、Dongmei Zhao、Maosheng Cheng

  DOI：10.1016/j.ejmech.2019.05.047

  日期：2019.9

  To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of l-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans

  为了发现广谱抗真菌剂，应用了两种策略，并且设计并合成了一类新型的1-氨基醇衍生物。3-F取代的化合物14i，14n，14s和14v表现出优异的抗真菌活性，对白念珠菌和热带念珠菌具有宽泛的抗真菌谱，MIC值在0.03-0.06μg/ mL范围内，对烟曲霉和C新甲虫，MIC值在1-2μg/ mL的范围内。值得注意的是，化合物14i，14n，14s和14v还显示出对从艾滋病患者中分离出的耐氟康唑耐药菌株17＃和CaR的中等活性。而且，仅S构型的化合物显示出抗真菌活性。初步的机理研究表明，化合物14v的有效抗真菌活性源于对白色念珠菌CYP51的抑制。化合物14n和14v对哺乳动物A549细胞几乎无毒，它们在人血浆中的稳定性非常好。
• New Auxiliaries for Copper-Catalyzed Asymmetric Michael Reactions: Generation of Quaternary Stereocenters at Room Temperature
  作者：Jens Christoffers、Alexander Mann

  DOI：10.1002/1521-3765(20010302)7:5<1014::aid-chem1014>3.0.co;2-x

  日期：2001.3.2

  Dialkyl amides of L-valine, L-isoleucine, and L-tert-leucine (2) are excellent chiral auxiliaries for the construction of quaternary stereocenters at ambient temperature. Enaminoesters 3, prepared from these auxiliaries 2 and Michael donors 1, undergo a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone (MVK, 4) to afford products 5 in 70-90% yield and 90-99% ee (enantiomeric excess)

  L-缬氨酸、L-异亮氨酸和 L-叔亮氨酸 (2) 的二烷基酰胺是在环境温度下构建四元立体中心的极佳手性助剂。由这些助剂 2 和迈克尔供体 1 制备的烯胺酯 3 与甲基乙烯基酮 (MVK, 4) 进行铜催化的不对称迈克尔反应，以 70-90% 的产率和 90-99% 的 ee（对映体过量）提供产物 5 . 不需要排除水分或氧气。助剂2可通过标准程序容易地获得。后处理后，它们几乎可以定量回收。
• Stereoselective Synthesis of 2-Alkenylaziridines and 2-Alkenylazetidines by Palladium-Catalyzed Intramolecular Amination of α- and β-Amino Allenes
  作者：Hiroaki Ohno、Miyuki Anzai、Ayako Toda、Shinya Ohishi、Nobutaka Fujii、Tetsuaki Tanaka、Yoshiji Takemoto、Toshiro Ibuka

  DOI：10.1021/jo015683v

  日期：2001.7.1

  Whereas palladium-catalyzed reaction of N-arylsulfonyl-alpha-amino allenes with an aryl iodide (4 equiv) in the presence of potassium carbonate (4 equiv) in DMF at around 70 degrees C affords the corresponding 3-pyrroline derivatives, the reaction in refluxing 1,4-dioxane under otherwise identical conditions yields exclusively or most predominantly the corresponding 2-alkenylaziridines bearing an aryl

  在碳酸钾（4当量）存在下，在DMF约70摄氏度下，钯催化N-芳基磺酰基-α-氨基丙二烯与碘代芳基碘（4当量）的反应可得到相应的3-吡咯啉衍生物在其他条件相同的条件下，回流1，4-二恶烷仅或最主要地产生在双键上带有芳基的相应的2-烯基氮丙啶。同样，在DMF中，在钯催化的环化条件下，N-芳基磺酰基-β-氨基丙二烯也可以环化成带有2,4-顺式构型的相应烯基氮杂环丁烷。
• A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
  作者：Saurav Bera、Gautam Panda

  DOI：10.1039/c4ob00639a

  日期：——

  synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium–copper co-catalytic system has

  通过分子内1,3-高效，通用和实用地合成各种3,4-二氢吡嗪，6,7-二氢-[1,2,3]三唑并吡嗪和7,8-二氢-[1,2,3]三唑并二氮杂pine描述了从氨基酸衍生的常见中间体以高收率进行偶极环加成。此外，在此方法中，还可以通过一锅获得光学活性的3-芳基取代的6,7-二氢-[1,2,3]三唑并[1,5- a ]吡嗪在钯-铜共催化体系中的应用。工作。容易获得的基材和操作简便性使该工艺适合于进一步探索。
• Synthesis of Enkephalin Analog with Leucinthiol at<i>C</i>-Terminus as Probe for Thiol Group in Opiate Receptors
  作者：Michio Kondo、Hiroaki Uchida、Hiroaki Kodama、Hiroshi Kitajima、Yasuyuki Shimohigashi

  DOI：10.1246/cl.1987.997

  日期：1987.5.5

  Enkephalin analog with thiol group at C-terminus, [D-Ala2, Leu(CH2SH)5]enkephalin, was synthesized as possible probe for the essential thiol group in opiate receptors. In order to protect the free SH group of leucinthiol, oxidized Boc-L-leucinthiol dimer was prepared from L-leucinol (2-amino-4-methyl-1-pentanol) to elongate the enkephalin sequence. SH-Containing monomeric enkephalin analog was obtained

  在 C 端具有硫醇基团的脑啡肽类似物 [D-Ala2, Leu(CH2SH)5] 脑啡肽被合成为阿片受体中必需硫醇基团的可能探针。为了保护亮氨酸硫醇的游离 SH 基团，从 L-亮氨酸（2-氨基-4-甲基-1-戊醇）制备氧化的 Boc-L-亮氨酸硫醇二聚体以延长脑啡肽序列。含 SH 的单体脑啡肽类似物是通过在 50% AcOH 中用锌处理从二聚体中获得的，它对 mu 阿片受体具有高亲和力。