N-(9-anthracenylmethyl)cinchonidinium chloride

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: N-(9-anthracenylmethyl)cinchonidinium chloride
• 英文别名: (1S,2S,4S,5R)-1-(anthracen-9-ylmethyl)-2-((R)-hydroxy(quinolin-4-yl)methyl)-5-vinyl-1-azoniabicyclo[2.2.2]octane chloride；anthracen-9-yl-methyl quininium chloride；(R)-[(2S,4S,5R)-1-(anthracen-9-ylmethyl)-5-ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl]-quinolin-4-ylmethanol;chloride
• 化学式: C₃₄H₃₃N₂O*Cl
• 分子量: 521.102
• InChiKey: PICKZKQBJJCSSV-YFKOWXRZSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(9-anthracenylmethyl)cinchonidinium chloride 、 二苯基溴甲烷 在 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 以43%的产率得到
  参考文献：
  名称：

  Catalytic Asymmetric Diaziridination

  摘要：

  The first catalytic enantio- and diastereoselective synthesis of diaziridines is presented. Aziridination of N-tosyl aldimines applying modified hydroxylamine under asymmetric phase-transfer catalysis furnished optically active diaziridines. The diaziridines are formed as a single diastereomer in up to 96% ee, containing two orthogonal N-protecting groups, which can be deprotected selectively.

  DOI：

  10.1021/ja401150m
• 作为产物：
  描述：

  9-氯甲基蒽 、 辛可尼丁 以 甲苯 为溶剂， 反应 6.0h， 生成 N-(9-anthracenylmethyl)cinchonidinium chloride
  参考文献：
  名称：

  β-芳基-β-异氰基酯的有机催化不对称合成

  摘要：

  在使用金鸡纳生物碱衍生的季铵盐的相转移催化下，丙二酸酯向原位生成的芳族醛的N-甲酰亚胺不对称加成反应。所得的β-甲酰胺基甲酸酯已经有效地转化为β-芳基-β-异氰基酯。已经证明了它们在与手性环状亚胺的多组分Ugi反应中的效用。

  DOI：

  10.1002/adsc.201200140
• 作为试剂：
  描述：

  1-methyl-4-[(2-nitroethyl)sulfinyl]benzene 、 碘甲烷 在 N-(9-anthracenylmethyl)cinchonidinium chloride 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 18.0h， 生成 (R)-(+)-甲基对甲苯砜 、 (S)-(-)-甲基对甲苯亚砜
  参考文献：
  名称：

  由金鸡纳衍生相转移试剂介导的亚磺酸阴离子的有机催化不对称合成亚砜

  摘要：

  本文描述了有关手性亚砜在手性相转移催化剂介导的亚磺酸盐与烷基卤化物的不对称烷基化的基础上获得手性亚砜的新颖方法的初步结果。作为代表性的例子，ö -anisyl甲基亚砜，96％收率和58％对映体过量使用商业金鸡尼丁衍生物制备2A。

  DOI：

  10.1021/ol2010962

文献信息

• Exploring Leishmania major Inositol Phosphorylceramide Synthase (LmjIPCS): Insights into the ceramide binding domain
  作者：John G. Mina、Jackie A. Mosely、Hayder Z. Ali、Paul W. Denny、Patrick G. Steel

  DOI：10.1039/c0ob00871k

  日期：——

  The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzymeLmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C13) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.

  本文描述了一组神经酰胺类似物的合成，这些类似物探讨了酰基链的疏水性、羟基化的程度和性质。它们已被用于检测寄生原生动物酶LmjIPCS。这些研究表明，尽管C-3羟基团对酶的代谢转化不是必需的，但它提供了增强的亲和力。鉴于该酶的膜结合性质，需要一个长（C13）碳氢神经酰胺尾部以实现高亲和力和代谢转化。虽然N-酰基链也对亲和力有所贡献，但缺乏酰胺键连接的类似物在酶和细胞基础测试中作为竞争性抑制剂发挥了作用。针对这一观察结果，我们提出了一个理论模型。
• Catalytic Asymmetric Hydrolysis: Asymmetric Hydrolytic Protonation of Enol Esters Catalyzed by Phase‐Transfer Catalysts
  作者：Eiji Yamamoto、Ayano Nagai、Akiyuki Hamasaki、Makoto Tokunaga

  DOI：10.1002/chem.201100833

  日期：2011.6.20

  Like an enzyme: Asymmetric hydrolysis of enol esters is accomplished by chiral phase‐transfer catalysts under biphasic base hydrolysis conditions. Stoichiometric reactions support the generation of a well‐organized chiral ammonium hydroxide species (Q+OH−).

  像酶一样：烯醇酯的不对称水解是通过手性相转移催化剂在双相碱水解条件下完成的。化学计量的反应支持一个组织良好的手性氢氧化铵物种（Q的生成+ OH - ）。
• [EN] SYNTHESIS OF 2-ALKYLCYSTEINES, 2-(HYDROXYLATED PHENYL)-4-ALKYLTHIAZOLINE-4-CARBOXYLIC ACIDS AND DERIVATIVES THEREOF<br/>[FR] SYNTHESE DES ACIDES 2-ALKYLCYSTEINES, 2-(PHENYLE HYDROXYLE)-4-ALKYLTHIAZOLINE-4-CARBOXYLIQUES ET DE LEURS DERIVES
  申请人：GENZYME CORP

  公开号：WO2003097622A2

  公开（公告）日：2003-11-27

  The present invention provides methods of preparing 2-alkylcysteine derivatives, many of which can be performed stereoselectively. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. An example of these iron chelating agents are 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-alkyl-thiazole-4-carboxylic acids, such as 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-thiazole-4-carboxylic acid.

  本发明提供了制备2-烷基半胱氨酸衍生物的方法，其中许多可以进行立体选择性。本发明还披露了一种制备与去铁蒺藜菌素相关的一类铁螯合剂的方法，所有这些铁螯合剂都含有噻唑环。这些铁螯合剂的一个例子是4,5-二氢-2-(2,4-二羟基苯基)-4-烷基噻唑-4-羧酸，例如4,5-二氢-2-(2,4-二羟基苯基)-4-甲基噻唑-4-羧酸。
• Synthesis of substituted thiazoline carboxylic acids
  申请人：Genzyme Corporation

  公开号：US20040082796A1

  公开（公告）日：2004-04-29

  A useful and efficient method of preparing an alkylated thiazoline carboxylic acid, or a derivative thereof, comprises coupling a substituted aryl nitrile such as, for example, 2,4-dimethoxybenzonitrile or 4-methoxybenzonitrile, with a cysteine ester to form a substituted thiazoline carboxylic acid ester; optionally hydrolyzing the substituted thiazoline carboxylic acid ester to form a substituted thiazoline carboxylic acid; optionally, protecting the carboxyl group; alkylating the thiazoline ring at the 4-carbon position, as indicated in Structural Formula (I), with a compound of the formula R 1 —L, wherein R 1 is as defined above and L is a leaving group, in the presence of a phase transfer catalyst; and, optionally, deprotecting the carboxyl group. In one embodiment of the present invention, a cinchona-alkaloid derived phase transfer catalyst is used to alkylate a protected substituted thiazoline carboxylic acid.

  一种制备烷基化噻唑啉羧酸或其衍生物的有用且高效方法包括：将取代芳基腈（例如2,4-二甲氧基苯腈或4-甲氧基苯腈）与半胱氨酸酯偶合形成取代噻唑啉羧酸酯；可选择水解取代噻唑啉羧酸酯形成取代噻唑啉羧酸；可选择保护羧基；在相转移催化剂存在下，用式R1-L的化合物烷基化噻唑啉环的4-碳位，如结构式（I）所示，其中R1如上所定义，L是一个离去基团；可选择去保护羧基。在本发明的一种实施例中，使用奎宁生物碱衍生的相转移催化剂烷基化保护的取代噻唑啉羧酸。
• Synthesis of 2-alkylcysteine via phase transfer catalysis
  申请人：Genzyme Corporation

  公开号：US20030236404A1

  公开（公告）日：2003-12-25

  Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. In one embodiment, the present invention provides methods of preparing 2-alkylcysteine derivatives. In another embodiment, the method comprises forming a 2-alkylcysteine derivative from a cysteine derivative in the presence of a phase transfer catalyst. In particular, the present invention provides methods for preparing 2-methylcysteine derivatives. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In one aspect, an aryl nitrile or imidate is condensed with cysteine or a 2-alkyl cysteine. The present invention also relates to the preparation of 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-alkyl-thiazole-4-carboxylic acids, such as 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-thiazole-4-carboxylic acid.

  非天然氨基酸（如2-烷基氨基酸）可以合成更广泛的肽类和非肽类药物活性剂。在一种实施例中，本发明提供了制备2-烷基半胱氨酸衍生物的方法。在另一种实施例中，该方法包括在相转移催化剂存在下从半胱氨酸衍生物形成2-烷基半胱氨酸衍生物。特别地，本发明提供了制备2-甲基半胱氨酸衍生物的方法。本发明还揭示了一种制备与去铁血胱铁类似的一类铁螯合剂的方法，其中所有铁螯合剂都含有噻唑环。在一个方面，芳基腈或亚胺酯与半胱氨酸或2-烷基半胱氨酸缩合。本发明还涉及制备4,5-二氢-2-(2,4-二羟基苯基)-4-烷基噻唑-4-羧酸，如4,5-二氢-2-(2,4-二羟基苯基)-4-甲基噻唑-4-羧酸。