(S)-(+)-2-phenyl-4-benzyloxycarbonyl-2-oxazoline | 609366-75-8

• 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: (S)-(+)-2-phenyl-4-benzyloxycarbonyl-2-oxazoline
• 英文别名: (S)-benzyl 2-phenyl-4,5-dihydrooxazole-4-carboxylate；benzyl (S)-4,5-dihydro-2-phenyloxazole-4-carboxylate；benzyl (4S)-2-phenyl-4,5-dihydrooxazole-4-carboxylate；benzyl (4S)-2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxylate
• CAS: 609366-75-8
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: FYUZXXDEUFNIPR-HNNXBMFYSA-N

物化性质

• 熔点：
  <40 °C
• 沸点：
  442.8±25.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(+)-2-phenyl-4-benzyloxycarbonyl-2-oxazoline 在 三氯溴甲烷 、 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 14.0h， 生成 2-苯基-4-噁唑羧酸
  参考文献：
  名称：

  Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds

  摘要：

  Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds-oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole,imidazo[1,2-a] pyridine, imidazo[1,2-a] pyrimidine and imidazo[1,2-c] pyrimidine-which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as < 0.195 mu M (9 and 11). Overall, the imidazo[1,2-a] pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi-and extensively resistant Mtb strains as well as having good in vitro metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.025
• 作为产物：
  描述：

  L-丝氨酸苄酯盐酸盐 在 potassium carbonate 、 N,N-二异丙基乙胺 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-(+)-2-phenyl-4-benzyloxycarbonyl-2-oxazoline
  参考文献：
  名称：

  Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds

  摘要：

  Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds-oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole,imidazo[1,2-a] pyridine, imidazo[1,2-a] pyrimidine and imidazo[1,2-c] pyrimidine-which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as < 0.195 mu M (9 and 11). Overall, the imidazo[1,2-a] pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi-and extensively resistant Mtb strains as well as having good in vitro metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.025

文献信息

• Catalytic Alkylation of 2-Aryl-2-oxazoline-4-carboxylic Acid Esters Using Cyclopeptoids; Newly Designed Phase-Transfer Catalysts
  作者：Giorgio Della Sala、Irene Izzo、Rosaria Schettini、Assunta D’Amato、Francesco De Riccardis

  DOI：10.1055/s-0036-1588102

  日期：——

  N-(4-methoxybenzyl)glycine/l-proline cyclohexapeptoid is the optimal catalyst (good yields and up to 75% ee) for the stereocontrolled construction of α-alkylated serine tert-butyl esters. Nonionic, chiral macrocyclic peptoids are efficient phase-transfer catalysts in the C-4 enantioselective alkylation of 2-[4-(trifluoromethyl)phenyl]-2-oxazoline-4-carboxylic acid esters. Screening of the structural features of cyclic

  摘要 非离子手性大环拟肽是2- [4-（三氟甲基）苯基] -2-恶唑啉-4-羧酸酯的C-4对映选择性烷基化反应中有效的相转移催化剂。筛选环状类肽的结构特征，即环大小，对称性，脯氨酸残基数和侧链上的取代基，表明交替的N-（4-甲氧基苄基）甘氨酸/ 1-脯氨酸环六肽是最佳催化剂（良好的收率和高达75％的ee）用于α-烷基化的丝氨酸叔丁酯的立体控制结构。 非离子手性大环拟肽是2- [4-（三氟甲基）苯基] -2-恶唑啉-4-羧酸酯的C-4对映选择性烷基化反应中有效的相转移催化剂。筛选环状类肽的结构特征，即环大小，对称性，脯氨酸残基数和侧链上的取代基，表明交替的N-（4-甲氧基苄基）甘氨酸/ 1-脯氨酸环六肽是最佳催化剂（良好的收率和高达75％的ee）用于α-烷基化的丝氨酸叔丁酯的立体控制结构。
• Efficient synthesis of β-halogeno protected l-alanines and their β-phosphonium derivatives
  作者：Franck Meyer、Abdelhamid Laaziri、Anna Maria Papini、Jacques Uziel、Sylvain Jugé

  DOI：10.1016/s0957-4166(03)00484-1

  日期：2003.8

  furnished the corresponding β-halogeno-N-benzoyl-α-amino acids in 70–95% yields. Quaternization of triphenylphosphine by the bromo or iodo derivatives led to the phosphonium salts bearing a free acid function in 95% yield, without racemization. The efficiency of this synthesis was demonstrated by the preparation of these phosphonium salts in excellent overall yields, by a one-pot procedure starting from the

  由1-丝氨酸制备的恶唑啉与三甲基甲硅烷基卤化物（TMSX）的开环导致β-卤代-N-苯甲酰基-α-氨基酯的产率高至优异。β-溴或-碘氨基酯对三苯膦进行季铵化可得到相应的β-salts盐，总收率可达93％，ee≥96％。酯官能团的水解得到带有N-苯甲酰基-α-氨基酸取代基的phospho盐，具有部分消旋作用。但是，TMSX与羧酸盐的反应是通过将起始的恶唑啉酯皂化而制备的，提供了相应的β-卤代-N-苯甲酰基-α-氨基酸，产率为70-95％。三苯基膦被溴或碘衍生物季铵化导致ization盐具有游离酸功能，产率为95％，而没有外消旋作用。通过从恶唑啉开始的一锅法以极好的总收率制备这些phospho盐，证明了这种合成的效率。
• A novel phosphorus–carbon bond formation by ring opening with diethyl phosphite of oxazolines derived from serine
  作者：Franck Meyer、Abdelhamid Laaziri、Anna Maria Papini、Jacques Uziel、Sylvain Jugé

  DOI：10.1016/j.tet.2004.03.001

  日期：2004.4

  A new reaction of oxazolines derived from serine with diethyl phosphite leading to ring opening products with P–C bond formation is reported. This reaction, which proceeds under neutral conditions and without the use of any halogenated intermediate, results in a mixture of racemic α- and β-phosphono alanines in an approximate 1:2 ratio, with isolated yields up to 77%. The mechanism involves the rearrangement

  据报道，由丝氨酸衍生的恶唑啉与亚磷酸二乙酯发生新反应，导致开环产物具有P–C键形成。该反应在中性条件下进行，无需使用任何卤代中间体，可生成外消旋α-和β-膦基丙氨酸的混合物，比例约为1：2，分离产率高达77％。该机理包括将恶唑啉重排成相应的α-苯甲酰胺基丙烯酸酯，然后将亚磷酸二乙酯加至双键。由于未观察到明显的酯交换，因此该方法为带有合适保护基团的α-和β-膦酰基氨基酸构成了简单的途径。
• Structure–activity relationship of new anti-tuberculosis agents derived from oxazoline and oxazole benzyl esters
  作者：Garrett C. Moraski、Mayland Chang、Adriel Villegas-Estrada、Scott G. Franzblau、Ute Möllmann、Marvin J. Miller

  DOI：10.1016/j.ejmech.2009.12.074

  日期：2010.5

  During the syntheses and studies of natural iron chelators (mycobactins), we serendipitously discovered that a simple, small molecule, oxazoline-containing intermediate 3 displayed surprising anti-tuberculosis activity (MIC of 7.7 μM, average). Herein we report elaboration of SAR around this hit as well as the syntheses and evaluation of a hundred oxazoline- and oxazole-containing compounds derived from

  在天然铁螯合剂（分枝杆菌素）的合成和研究过程中，我们偶然发现一种简单的小分子含恶唑啉中间体3表现出令人惊讶的抗结核活性（平均MIC为7.7 μM）。在此，我们报告了围绕这一打击的 SAR 详细阐述，以及从有效的三步过程衍生的一百种含恶唑啉和恶唑化合物的合成和评估：1）与丝氨酸或苏氨酸形成 β-羟基酰胺； 2)环化得到恶唑啉； 3)脱水得到相应的恶唑。通过这种方法制备的许多化合物显示出具有令人印象深刻的抗结核分枝杆菌活性、极低的毒性和因此高的治疗指数，以及对更顽固的非复制形式的结核分枝杆菌的活性。它们结构的独特性和简单性应该使它们能够进一步优化以满足 ADME（吸收、分布、代谢、排泄）要求。八种最有效的体外化合物的合成得到了扩大，并在小鼠体内感染模型中测试了这些化合物，以评估其功效，然后再进行更精细的化合物设计和优化。
• <i>N</i>-((1-Benzyl-1<i>H</i>-1,2,3-triazol-4-yl)methyl)arylamide as a New Scaffold that Provides Rapid Access to Antimicrotubule Agents: Synthesis and Evaluation of Antiproliferative Activity Against Select Cancer Cell Lines
  作者：Jonathan A. Stefely、Rahul Palchaudhuri、Patricia A. Miller、Rebecca J. Peterson、Garrett C. Moraski、Paul J. Hergenrother、Marvin J. Miller

  DOI：10.1021/jm1000979

  日期：2010.4.22

  A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC50 of 46 nM against MCF-7 human breast tumor cells. Structure activity relationship (SA R) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G(2)/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.