(+/-)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester | 68641-86-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (+/-)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester
• 英文别名: butyl 2-(6-methoxy-2-naphthyl)propanoate；(R,S)-naproxen n-butyl ester；(A+/-)-Naproxen butyl ester；butyl 2-(6-methoxynaphthalen-2-yl)propanoate
• CAS: 68641-86-1
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: VIKFUEUFSFCFQU-UHFFFAOYSA-N

物化性质

• 熔点：
  52-53 °C
• 沸点：
  400.4±20.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 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：

  (+/-)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester 在 phosphate buffer 作用下， 以 异辛烷 为溶剂， 生成 萘普生
  参考文献：
  名称：

  Influence of OR ester group length on the catalytic activity and enantioselectivity of free lipase and immobilized in membrane used for the kinetic resolution of naproxen esters

  摘要：

  Lipases are suitable catalysts for the kinetic resolution of racemic mixtures due to their ability to discriminate between enantiomers. For this reason, they have been studied largely to develop reactors for the production of optically pure enantiomers. The main problem in these productive systems is enzyme stability and enantiocatalytic selectivity as a function of time. In this work, the enantiocatalytic properties of lipase as a function of the -OR group length were studied. The methyl, butyl, and octyl esters of naproxen were synthesized and used as reagents. The lipase was used as a free agent and immobilized in a polymeric membrane reactor. The results show that selectivity and stability of the enzyme improved while catalytic activity decreased with the -OR length group. The immobilized enzyme had higher activity compared with the free enzyme. (C) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jcat.2007.01.021
• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 、 正丁醇 在 氯化亚砜 作用下， 反应 2.0h， 以75%的产率得到(+/-)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester
  参考文献：
  名称：

  Influence of OR ester group length on the catalytic activity and enantioselectivity of free lipase and immobilized in membrane used for the kinetic resolution of naproxen esters

  摘要：

  Lipases are suitable catalysts for the kinetic resolution of racemic mixtures due to their ability to discriminate between enantiomers. For this reason, they have been studied largely to develop reactors for the production of optically pure enantiomers. The main problem in these productive systems is enzyme stability and enantiocatalytic selectivity as a function of time. In this work, the enantiocatalytic properties of lipase as a function of the -OR group length were studied. The methyl, butyl, and octyl esters of naproxen were synthesized and used as reagents. The lipase was used as a free agent and immobilized in a polymeric membrane reactor. The results show that selectivity and stability of the enzyme improved while catalytic activity decreased with the -OR length group. The immobilized enzyme had higher activity compared with the free enzyme. (C) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jcat.2007.01.021

文献信息

• Alkylating Polymers: Resin-Released Carbenium Ions as Versatile Reactive Intermediates in Polymer-Assisted Solution-Phase Synthesis
  作者：Jörg Rademann、Joachim Smerdka、Günther Jung、Philipp Grosche、Dietmar Schmid

  DOI：10.1002/1521-3773(20010119)40:2<381::aid-anie381>3.0.co;2-v

  日期：2001.1.19

  Solid-supported diazoalkane analogues for the smooth and clean esterifications of carboxylic acids [Eq. (1)] as well as of complex compound mixtures: the alkylating polymers presented here were synthesized as solid-supported 3-alkyl-1-aryltriazenes and are capable of releasing carbenium ions following acidic activation.

  固体负载的重氮烷烃类似物，用于羧酸的平滑和清洁酯化反应[式]。（1）]以及复杂的化合物混合物：此处介绍的烷基化聚合物是作为固体负载的3-烷基-1-芳基三氮烯合成的，能够在酸性活化后释放碳正离子。
• A Great Improvement of the Enantioselectivity of Lipase-Catalyzed Hydrolysis and Esterification Using Co-Solvents as an Additive
  作者：Tomohiro Nishigaki、Yoshitaka Yasufuku、Sayuri Murakami、Yasuhito Ebara、Shin-ichi Ueji

  DOI：10.1246/bcsj.81.617

  日期：2008.5.15

  improvement of the enantioselectivity of lipase-catalyzed hydrolysis of butyl 2-(4-substituted phenoxy)propanoates in an aqueous buffer solution. On the other hand, lipase lyophilized from an aqueous solution containing the co-solvents catalyzed highly enantioselective esterification of 2-(4-substituted phenoxy)propionic acids, 2-(4-isobutylphenyl)propionic acid (ibuprofen), and 2-(6-methoxy-2-naphthyl)propionic

  添加共溶剂如四氢呋喃导致脂肪酶催化的 2-(4-取代苯氧基)丙酸丁酯在缓冲水溶液中水解的对映选择性大大提高。另一方面，从含有共溶剂的水溶液中冻干的脂肪酶催化 2-（4-取代苯氧基）丙酸、2-（4-异丁基苯基）丙酸（布洛芬）和 2-（6 -甲氧基-2-萘基）丙酸（萘普生）在有机溶剂中。对于某些底物，观察到 E 值增加了两个数量级。由共溶剂添加引起的对映选择性增强的起源主要归因于错误结合的对映异构体的初始反应速率显着减慢，与正确结合的对映体相比。从FT-IR、CD和ESR光谱的结果来看，还发现共溶剂的加入导致脂肪酶三级结构的部分破坏。
• Process for the optical resolution of racemic mixtures of alpha-naphthyl-propionic acids
  申请人：Alfa Chemicals Italiana S.r.l.

  公开号：EP0143371A1

  公开（公告）日：1985-06-05

  A new process for the optical resolution of racemic mixtures of α-naphthyl-propionic acids of formula This process comprises reacting a racemic mixture of a compound of formula with an optically active substance of formula R4-NH2 (III), said substance being a β-aminoalcohol, thus forming a pair of diastereoisomeric amides which are resolved into the single diastereoisomers by fractional crystallization. The obtained single diastereoisomeric amide is then hydrolized to give the desired optically active α-naphthyl-propionic acid of formula In the above compound I → III and VI, R, is (C1-6)alkyl, R2 stands for hydrogen, halogen, mercapto, (C1-6)alkylthio, phenylthio, benzylthio (C1-6)alkylsulfonyl, benzenesulfonyl, benzenesulfonyl substituted by halogen or (C1-4)alkyl, R3 is a reactive group and R4 is the residue of a primary or secondary alcohol.

  式α-萘基丙酸外消旋混合物的光学解析新工艺 该工艺包括将一种式化合物的外消旋混合物与一种式 R4-NH2 (III) 的光学活性物质反应。 与一种光学活性物质 R4-NH2 (III)（所述物质为 β-氨基醇）反应，从而形成一对非对映异构体酰胺，通过分馏结晶将其分解为单一非对映 异构体。然后将得到的单一非对映异构体酰胺水解，得到所需的光学活性 α-萘基丙酸，其式为 在上述化合物Ⅰ→Ⅲ和Ⅵ中，R是(C1-6)烷基，R2代表氢、卤素、巯基、(C1-6)烷硫基、苯硫基、苄硫基、(C1-6)烷磺酰基、苯磺酰基、被卤素或(C1-4)烷基取代的苯磺酰基，R3是活性基团，R4是伯醇或仲醇的残基。
• A method to greatly improve the enantioselectivity of lipase-catalyzed hydrolysis using sodium dodecyl sulfate (SDS) as an additive
  作者：Shuichi Mori、Hiromi Yumoto、Rina Matsumi、Tomohiro Nishigaki、Yasuhito Ebara、Shin-ichi Ueji

  DOI：10.1016/j.tetasy.2005.10.003

  日期：2005.11

  The addition of sodium dodecyl sulfate (SDS) resulted in a dramatic improvement of the enantioselectivity of the lipasecatalyzed hydrolysis of racemic butyl 2-(4-substituted phenoxy)propanoates, racemic butyl 2-(4-isobutylphenyl)propanoate, and racemic butyl 2-(6-methoxy-2-naphthyl)propanoate in an aqueous buffer solution. An increase in the E value by up to two orders of magnitude was observed for some esters. As to the effects of SDS on the structure of a lipase, FT-IR and fluorescence measurements suggest some conformational change and/or an increase of the flexibility of the lipase, although the native secondary structure of the lipase is held even in the presence of 100 mM SDS. The origin of the enantioselectivity enhancement brought about by the addition of SDS is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate. (c) 2005 Elsevier Ltd. All rights reserved.
• Enzymatic resolution of naproxen
  作者：Surrinder Koul、Rajinder Parshad、Subhash C. Taneja、Ghulam N. Qazi

  DOI：10.1016/s0957-4166(03)00492-0

  日期：2003.8

  Trichosporon sp. (TSL), a newly found strain isolated from a locally fermented cottage cheese has been found to be highly stereoselective in the resolution of (S)-(+)-naproxen (ee >99%, Esimilar to500) from the corresponding racemic methyl ester. The process of resolution using whole cells has been scaled up to multi-kg level. Optimization of experimental conditions including downstream processing at 80-100 g/L substrate concentration with >90% recovery has been achieved. Changes in the physical parameters such as the particle size of the substrate play an important role in the resolution kinetics. A new strain of Trichosporon sp. having high cell density in cultivation (>60 g dry cell mass L-1 in 14-16 h) is found to be sufficiently stable for two years in dry powder form at 5-8degreesC. The viability of the resolution process has been further improved by the development of a simple racemization process for the enriched (R)-(-)-ester. (C) 2003 Elsevier Ltd. All rights reserved.