(5S)-3-tert-butyl-5-hydroxymethyloxazolidin-2-one | 56526-14-8

• 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: (5S)-3-tert-butyl-5-hydroxymethyloxazolidin-2-one
• 英文别名: (S)-(+)-5-(hydroxymethyl)-3-tert-butyloxazolidin-2-one；(S)-(+)-3-t-butyl-5-hydroxymethyloxazolidin-2-one；(5S)-3-tert-butyl-5-(hydroxymethyl)-1,3-oxazolidin-2-one
• CAS: 56526-14-8
• 化学式: C₈H₁₅NO₃
• 分子量: 173.212
• InChiKey: SSMIUHOOMMVZNL-LURJTMIESA-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：

  (5S)-3-tert-butyl-5-hydroxymethyloxazolidin-2-one 在 sodium hydroxide 、 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 喷布洛尔
  参考文献：
  名称：

  Kan, Kazunori; Miyama, Akimasa; Hamaguchi, Shigeki, Agricultural and Biological Chemistry, 1985, vol. 49, # 1, p. 207 - 210

  摘要：

  DOI：
• 作为产物：
  描述：

  (R)-3-N-ethoxycarbonyl-N-tert-butylamino-1,2-epoxypropane 在 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以87%的产率得到(5S)-3-tert-butyl-5-hydroxymethyloxazolidin-2-one
  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

文献信息

• Biological resolution of racemic 2-oxazolidinones. Part I. Asymmetric hydrolysis of (R,S)-5-acetoxymethyl-3-tert-butyl-oxazolidin-2-one with enzymes and microorganisms.
  作者：Shigeki HAMAGUCHI、Junzo HASEGAWA、Hajime KAWAHARADA、Kiyoshi WATANABE

  DOI：10.1271/bbb1961.48.2055

  日期：——

  Enzymes and microorganisms were screened for the asymmetric hydrolysis of (R, S)-5-acetoxymethyl-3-tert-butyl-oxazolidin-2-one 1. Lipases from Pseudomonas aeruginosa and Alcaligenes species, and microorganisms which belong to Enterobacter species or Klebsiella species were found to hydrolyze 1 enantioselectively to give (R)-5-hydroxymethyl-3-tert-butyl-oxazolidin-2-one (R)-2 and (S)-1. (S)-2, one of the typical intermediates for preparing optically active β-blocking agents (β-blockers), was obtained with high enantiomeric excess (91- 98% e.e.) from (S)-1.

  筛选用于不对称水解 (R,S)-5-乙酰氧基甲基-3-叔丁基-恶唑烷-2-酮 1. 来自铜绿假单胞菌和产碱杆菌属物种的脂肪酶，以及属于肠杆菌属物种或克雷伯氏菌属的微生物发现物种对映选择性水解1，得到(R)-5-羟甲基-3-叔丁基-恶唑烷-2-酮(R)-2和(S)-1。 (S)-2是制备光学活性β-阻断剂（β-阻断剂）的典型中间体之一，由(S)-1以高对映体过量（91-98% e.e.）获得。
• Process for production of optically active oxazolidinone derivative
  申请人：Kanegafuchi Kagaku Kogyo Kabushiki Kaisha

  公开号：US04588694A1

  公开（公告）日：1986-05-13

  A process for preparing the optically active oxazolidinone derivative [(S)-I] by utilizing microorganisms or enzymes having a stereoselective esterase activity capable of asymmetrically hydrolyzing the racemates of the acyloxyoxazolidinone derivative [(R,S)-II], by separating the unreacted compound [(S)-II] from the hydrolyzed compound [(R)-I] and by hydrolyzing the compound [(S)-II]. The compounds are useful as intermediates for preparing optically active .beta.-adrenergic blocking agents.

  一种制备光学活性的噁唑啉酮衍生物[(S)-I]的方法，利用具有立体选择性酯酶活性的微生物或酶，能够对酰氧噁唑啉酮衍生物[(R,S)-II]的外消旋体进行不对称水解，通过将未反应的化合物[(S)-II]与水解后的化合物[(R)-I]分离，并对化合物[(S)-II]进行水解。这些化合物可用作制备光学活性β-肾上腺素受体阻滞剂的中间体。
• 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%。
• 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。