(R)-5-hydroxymethyl-3-tert-butyl-2-oxazolodinone | 98048-84-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (R)-5-hydroxymethyl-3-tert-butyl-2-oxazolodinone
• 英文别名: (R)-5-hydroxymethyl-3-tert-butyl-oxazolin-2-one；(5R)-3-tert-butyl-5-(hydroxymethyl)-1,3-oxazolidin-2-one
• CAS: 98048-84-1
• 化学式: C₈H₁₅NO₃
• 分子量: 173.212
• InChiKey: SSMIUHOOMMVZNL-ZCFIWIBFSA-N

物化性质

• 沸点：
  343.3±15.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-5-hydroxymethyl-3-tert-butyl-2-oxazolodinone 在 sodium hydroxide 、 水 、 氢溴酸 、 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 (R)-3-N-ethoxycarbonyl-N-tert-butylamino-1,2-epoxypropane
  参考文献：
  名称：

  Biological resolution of racemic 2-oxazolidinones. Part VI. Stereochemical inversion of (R)-5-hydroxymethyl-3-tert-butyl-2-oxazolidinone or (R)-5-hydroxymethyl-3-isopropyl-2-oxazolidinone to the corresponding (S)-isomer.

  摘要：

  (R)-5-羟甲基-3-叔丁基-2-恶唑烷酮（1a）或(R)-5-羟甲基-3-异丙基-2-恶唑烷酮（1b）的立体化学反转，通过关键中间体(R)-3-N-乙氧羰基-N-叔丁基氨基-1,2-环氧丙烷（5a）或(R)-3-N-乙氧羰基-N-异丙基氨基-1,2-环氧丙烷（5b），以高对映体过量成功转化为相应的(S)-异构体。因此，分别从相应的(R)-异构体（1a；99% e.e.，1b；95% e.e.）得到了(S)-1a（99% e.e.）或(S)-1b（97% e.e.）。

  DOI：

  10.1271/bbb1961.49.1669
• 作为产物：
  描述：

  5-(羟基甲基)-3-(2-甲基-2-丙基)-1,3-恶唑烷-2-酮 在 sodium hydroxide 作用下， 以 苯 为溶剂， 反应 4.7h， 生成 (R)-5-hydroxymethyl-3-tert-butyl-2-oxazolodinone
  参考文献：
  名称：

  Anhydrides as acylating agents in lipase-catalyzed stereoselective esterification of racemic alcohols

  摘要：

  DOI：

  10.1021/jo00258a024

文献信息

• Asymmetric Hydrolysis of Racemic 2-Oxazolidinone Esters with Lipases
  作者：Shigeki Hamaguchi、Masanori Asada、Junzo Hasegawa、Kiyoshi Watanabe

  DOI：10.1080/00021369.1984.10866481

  日期：1984.9.1

  The enzymatic hydrolysis of (R, S)-5-acyloxymethyl-3-alkyl-oxazolidin-2-one I and the behavior of (S)-I for extraction with an organic solvent were examined so as to extend the biological resolution to racemates, and to learn about more appropriate combinations of substrates with lipases on the asymmetric hydrolysis. The combination of (R, S)-5-hexanoyloxymethyl-3-tert-butyl-oxazolidin-2-one 4 with lipoprotein lipase Amano 3 (L. P. L. Amano 3, origin; Pseudomonas aeruginosa) and that of (R, S)-5-octanoyloxymethyl-3-isopropyl-oxazolidin-2-one 14 with L. P. L. Amano 3 efficiently gave (S)-5-hydroxymethyl-3-tert-butyl-oxazolidin-2-one (S)-lla (99% e.e.) and (S)-5-hydroxymethyl-3-isopropyl-oxazolidin-2-one (S)-IIb (99% e.e.),respectively. (S)-IIa and (S)-IIb could be considered to be favorable intermediates for preparing optically active β-blockers.

  研究了(R, S)-5-己酰氧基甲基-3-烷基-恶唑啉-2-酮 I 的酶水解以及 (S)-I 用有机溶剂萃取的行为，以便将生物分辨率扩展到外消旋体，并了解底物与脂肪酶在不对称水解中的更合适组合。(R,S)-5-己酰氧甲基-3-叔丁基-噁唑烷-2-酮 4 与脂蛋白脂肪酶天野 3（L. P. L. Amano 3，原产地；铜绿假单胞菌）的组合，以及(R,S)-5-辛酰氧甲基-3-异丙基-噁唑烷-2-酮 14 与 L. P. L. Amano 3 的组合，都能有效地水解脂蛋白脂肪酶。P. L. Amano 3 分别有效地得到了(S)-5-羟甲基-3-叔丁基-噁唑烷-2-酮(S)-lla (99% e.e.)和(S)-5-羟甲基-3-异丙基-噁唑烷-2-酮(S)-IIb (99% e.e.)。(S)-IIa和(S)-IIb可被视为制备光学活性β-受体阻滞剂的有利中间体。
• Biological resolution of racemic 2-oxazolidinones. Part V. Stereospecific hydrolysis of 2-oxazolidinone esters and separation of products with an immobilized lipase column.
  作者：Shigeki HAMAGUCHI、Masanori ASADA、Junzo HASEGAWA、Kiyoshi WATANABE

  DOI：10.1271/bbb1961.49.1661

  日期：——

  Hydrophobic (R, S)-5-acyloxymethyl-3-alkyl-2-oxazolidinones were successfully hydrolyzed stereospecifically with lipoprotein lipase Amano 3 (LPL) adsorbed on Amberlite XAD-7. The LPL immobilized on the resin was not desorbed on washing with phosphate buffer, toluene or hexane. The activity loss of the column was little during storage for five months at room temperature. Stereospecific hydrolyses were performed pulsewise with the column, and separation of the hydrophobic (S)-ester from the hydrophilic (R)-alcohol was also performed on the same column utilizing the hydrophobic interaction between the (S)-ester and the support resin. The immobilized LPL column was stable on repetition of these operations for over 20 times. The optical purities of the obtained (S)-oxazolidinones, which were favorable intermediates for the synthesis of (S)-β-blockers, were 96-98% e.e.

  用吸附在 Amberlite XAD-7 上的脂蛋白脂肪酶天野 3（LPL）成功地立体定向水解了疏水性（R，S）-5-乙酰氧基甲基-3-烷基-2-恶唑烷酮。用磷酸盐缓冲液、甲苯或正己烷洗涤时，固定在树脂上的 LPL 不会解吸。在室温下储存五个月后，色谱柱的活性损失很小。利用该色谱柱进行了立体特异性水解，并在同一色谱柱上利用(S)-酯和支撑树脂之间的疏水作用分离了疏水的(S)-酯和亲水的(R)-醇。固定化 LPL 色谱柱在重复上述操作 20 多次后保持稳定。获得的(S)-噁唑烷酮是合成(S)-β-受体阻滞剂的有利中间体，其光学纯度为 96-98%。
• Bifunctional heterocyclic compounds and methods of making and using same
  申请人：Wang Deping

  公开号：US20080119419A1

  公开（公告）日：2008-05-22

  The invention provides a family of bifunctional heterocyclic compounds useful as anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. The invention also provides methods of making the bifunctional heterocyclic compounds, and methods of using such compounds as anti-infective, anti-proliferative agents, anti-inflammatory, and/or prokinetic agents.

  本发明提供了一系列双功能杂环化合物，可作为抗感染、抗增殖、抗炎和促动力药物使用。本发明还提供了制备双功能杂环化合物的方法，以及使用这些化合物作为抗感染、抗增殖剂、抗炎剂和/或促动力剂的方法。
• BENZOXAZINE OXAZOLIDINONE COMPOUND, PREPARATION METHOD AND APPLICATION THEREOF
  申请人：SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

  公开号：US20150336984A1

  公开（公告）日：2015-11-26

  Disclosed are a benzoxazine oxazolidinone compound shown by a general formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, a preparation method thereof, and an application thereof in preparing a drug for treating an infectious disease and in particular, an infectious disease caused by multidrug resistant bacteria.

  本发明涉及一种由通式(I)表示的苯并噁唑噁唑烷化合物、其光学异构体或其药学上可接受的盐，其制备方法以及其在制备治疗感染病的药物中的应用，特别是在治疗多重耐药细菌引起的感染病中的应用。
• A process for the enzymatic separation of the optical isomers of racemic oxazolidinonic derivatives
  申请人：Montedison S.p.A.

  公开号：EP0274277A2

  公开（公告）日：1988-07-13

  A process for the separation of a racemic mixture of the S(+) and R(-) optical isomers of an oxazolidinone compound of the formula: (in which R is a straight or branched C₁-C₈ alkyl group) which process comprises reacting the racemic 3-alkyl-5-hydroxy-methyl-oxazolidin-2-one derivative of formula (I) with an esterifying compound which is (a) an ester of the formula: (in which Rʹ is a straight or branched C₁-C₁₀ alkyl or alkenyl group, and Rʺ is a straight or branched C₁-C₄ alkyl or alkenyl group, a haloalkyl group or a diacylglycerolic group), (b) an acid of the formula:       Rʺʹ-COOH      (V) (in which Rʺʹ is a straight or branched C₁-C₂₀ alkyl or alkenyl group) or (c) an anhydride of the formula: (in which RIV is a straight or branched C₁-C₆ alkyl group)       the reaction being carried out in the presence of an enzyme, immobilized on a porous carrier, capable of selectively giving rise to the esterification of the R(-) isomer, while leaving the S(+) isomer of the racemic starting compound of formula (I) substantially unchanged;       and separating the S(+) isomer.

  一种分离式中噁唑烷酮化合物的 S(+)和 R(-)光学异构体的外消旋混合物的工艺： (其中 R 为直链或支链 C₁-C₈烷基），该工艺包括将式（I）的外消旋 3-烷基-5-羟甲基-噁唑烷-2-酮衍生物与酯化化合物反应，该酯化化合物为 (a) 式中的酯： (其中 Rʹ 是直链或支链 C₁-C₁₀ 烷基或烯基，Rʺ 是直链或支链 C₁-C₄ 烷基或烯基、卤代烷基或二酰基甘油基）、 (b) 式中的酸： Rʺʹ-COOH (V) (其中 Rʺʹ 是直链或支链 C₁-C₂₀ 烷基或烯基）或 (c) 式中的酸酐： (其中 RIV 为直链或支链 C₁-C₆烷基）。 该反应在固定于多孔载体上的酶存在下进行，该酶能够选择性地引起 R（-）异构体的酯化，而使式（I）外消旋起始化合物的 S（+）异构体基本保持不变； 分离 S(+)异构体。