(+/-)-Methyl α-methoxy-α-(2-naphthyl)acetate | 160727-71-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (+/-)-Methyl α-methoxy-α-(2-naphthyl)acetate
• 英文别名: methyl methoxy(2-naphthyl)acetate；methyl 2-methoxy-2-(naphthalen-2-yl)acetate；methyl 2-methoxy-2-naphthalen-2-ylacetate
• CAS: 160727-71-9
• 化学式: C₁₄H₁₄O₃
• 分子量: 230.263
• InChiKey: XWWLSMSDYNKMIM-UHFFFAOYSA-N

物化性质

• 沸点：
  362.9±22.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-Methyl α-methoxy-α-(2-naphthyl)acetate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以47%的产率得到2-Methoxy-2-(naphthalen-2-yl)acetohydrazide
  参考文献：
  名称：

  PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS

  摘要：

  揭示了抑制PDE10的化合物，可用于治疗多种疾病，包括（但不限于）精神病、焦虑、运动障碍和/或神经系统疾病，如帕金森病、亨廷顿病、阿尔茨海默病、脑炎、恐惧症、癫痫、失语症、贝尔氏面瘫、脑性瘫痪、睡眠障碍、疼痛、抽动症、精神分裂症、妄想症、药物诱导的精神病和惊恐症以及强迫症。此外，还提供了这些化合物的药用盐、立体异构体、溶剂合物和前药。还揭示了含有化合物的组合物，与药用载体结合，以及与使用这些组合物抑制温血动物中的PDE10相关的方法。

  公开号：

  US20100035872A1
• 作为产物：
  描述：

  2-naphthyl cyanohydrin 在 phosphate buffer 、 nitrosylsulfuric acid 、 Amberlyst-15 H⁺ form 、 Rhodococcus rhodochrous IFO 15564 、 tin(II) bromide 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.17h， 生成 (+/-)-Methyl α-methoxy-α-(2-naphthyl)acetate
  参考文献：
  名称：

  化学酶促合成对映体纯的（R）-2-萘甲氧基乙酸

  摘要：

  对映体纯的（R）-2-萘甲氧基乙酸（2-NMA）是由2-萘醛通过整合的化学酶促程序合成的。单锅连续使用SnBr 2 -TMSCN和AcBr可以有效地产生外消旋氰醇乙酸酯。然后来自洋葱伯克霍尔德氏菌的脂肪酶介导外消旋物的（S）-对映体的高度对映选择性水解，使（R）-乙酸酯的ee大于99.9％。将得到的这种酶催化水解，一个的产物（小号）-氰醇自发地分解为萘甲醛（该合成途径的起始原料），可以回收利用。在非常温和的条件下，用微生物Rhodococcus rhodochrous将腈水合成酰胺，以及将乙酸酯水解，而不会损失任何对映体纯度。用亚硝酰基硫酸水解酰胺基，并分离出产物，为α-羟基酯。用重氮甲烷硅胶将α-羟基甲基化，最后的任务是酯水解，在中等至中等pH的条件下，用产自克雷伯氏菌的酯酶进行酯化，得到对映体纯的2-NMA。

  DOI：

  10.1016/s0957-4166(02)00242-2

文献信息

• Brønsted Acid Catalyzed Formal Insertion of Isocyanides into a C−O Bond of Acetals
  作者：Mamoru Tobisu、Aki Kitajima、Sachiko Yoshioka、Isao Hyodo、Masayuki Oshita、Naoto Chatani

  DOI：10.1021/ja073286h

  日期：2007.9.1

  the structure of the isocyanide. The use of an electron-deficient aryl isocyanide, such as 2c and 2d, is required to selectively obtain the monoinsertion product. When aryl isocyanides containing alkyl substituents, such as 2a and 2b, are employed, two molecules of the isocyanide are incorporated, and the double-insertion product is obtained. The reaction of tert-octyl isocyanide also induces a double

  描述了布朗斯台德酸催化异氰化物正式插入缩醛的 CO 键。各种非环状和环状缩醛可以应用于催化插入以形成 α-烷氧基亚胺酸酯。官能团，例如硝基、氰基、卤素、酯和烷氧基，可以耐受所采用的反应条件。反应过程高度依赖于异氰化物的结构。需要使用缺电子的芳基异氰化物，例如 2c 和 2d，以选择性地获得单插入产物。当使用含有烷基取代基的芳基异氰化物，例如2a和2b时，引入两个分子的异氰化物，得到双插入产物。叔辛基异氰化物的反应也诱导了双重掺入，但随后的酸介导的断裂会导致 2-烷氧基亚胺酰氰化物。单插入产物 α-烷氧基亚胺酸酯可以很容易地水解为 α-烷氧基酯，从而实现缩醛的正式羰基化。
• A Laser Flash Photolysis Study of 2-Naphthyl(carbomethoxy)carbene
  作者：Jen-Lung Wang、Igor Likhotvorik、Matthew S. Platz

  DOI：10.1021/ja983279g

  日期：1999.3.1

  Photolysis of methyl 2-diazo(2-naphthyl)acetate releases singlet 2-naphthyl(carbomethoxy)carbene. The singlet carbene relaxes to the lower energy triplet state within 350 ps−1 ns. Singlet to triplet carbene intersystem crossing is much faster than Wolff rearrangement to the corresponding ketene. The barrier to Wolff rearrangement of the spin-equilibrated carbene is 3.4 kcal/mol in hexafluorobenzene

  2-重氮（2-萘基）乙酸甲酯的光解释放单线态 2-萘基（甲氧基）卡宾。单线态卡宾在 350 ps-1 ns 内弛豫到较低能量的三线态。单线态到三线态卡宾系统间的交叉比沃尔夫重排到相应的乙烯酮要快得多。在六氟苯中，自旋平衡的卡宾发生沃尔夫重排的障碍为 3.4 kcal/mol。在该系统中，烯酮由卡宾形成，并且在很大程度上不是由重氮化合物的激发态形成。
• PDE10 inhibitors and related compositions and methods
  申请人：Cutshall Neil S.

  公开号：US08377930B2

  公开（公告）日：2013-02-19

  Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

  本文披露了抑制PDE10的化合物，该化合物在治疗多种疾病方面具有用途，包括（但不限于）精神病、焦虑症、运动障碍和/或神经系统疾病，如帕金森病、亨廷顿病、阿尔茨海默病、脑炎、恐惧症、癫痫、失语症、贝尔氏麻痹症、脑瘫、睡眠障碍、疼痛、抽动症、精神分裂症、妄想症、药物诱发的精神病和惊恐和强迫症。此外，还提供了该化合物的药物可接受的盐、立体异构体、溶剂物和前药。本文还披露了含有化合物与药物可接受的载体组合的组合物，以及与使用该组合物抑制需要同样的温血动物的PDE10相关的方法。
• Synthesis of novel proxyphylline derivatives with dual Anti-Candida albicans and anticancer activity
  作者：Paweł Borowiecki、Patrycja Wińska、Maria Bretner、Małgorzata Gizińska、Mirosława Koronkiewicz、Monika Staniszewska

  DOI：10.1016/j.ejmech.2018.02.077

  日期：2018.4

  Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R >= 3 at conc. of 31, 36 and 20 mu M, respectively) however not against normal mammalian Vero cell line in vitro (IC50 >= 280 mu M) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 mu M) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3-6.5 mu M). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Conformational Structure and Dynamics of Arylmethoxyacetates: DNMR Spectroscopy and Aromatic Shielding Effect
  作者：Sh. K. Latypov、J. M. Seco、E. Quinoa、R. Riguera

  DOI：10.1021/jo00108a008

  日期：1995.2

  The ground state conformational geometry and energy of esters of (R)- and (S)-arylmethoxyacetic acids were evaluated from low temperature H-1 and C-13 NMR spectra and by means of MM, AM1, and aromatic shielding effect calculations. In solution, the title compounds are constituted by two rotamers in equilibrium. Rotamer ap has the C-alpha-O and C=O bonds antiperiplanar and rotamer sp (lower in energy by 0.4-1.1 kcal/mol) has these bonds synperiplanar. In both the ap and the sp the aryl ring is ca. perpendicular to the C=O bond and coplanar with the CalphaH bond. Their relative populations and its temperature dependence evaluated by DNMR spectra are in agreement with the stereoselectivity reported for Diels-Alder reactions of dienyl-AMAA esters and support the ''perpendicular model'' proposed to account for that stereoselectivity. For conformations in which the aryl ring shields the alcohol moiety of the ester, calculated ring current shielding increments compare well with experimental shift values obtained from low-temperature NMR spectra and agree with the conformational model used in the Mislow-Dale-Mosher-Trost method for chiral recognition by NMR.