(R)-6'-Hydroxybuspirone | 477930-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (R)-6'-Hydroxybuspirone
• 英文别名: (R)-6-hydroxy-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]-butyl]-8-azaspiro[4.5]decane-7,9-dione；(R)-6-hydroxybuspirone；(10R)-10-hydroxy-8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione
• CAS: 477930-30-6
• 化学式: C₂₁H₃₁N₅O₃
• 分子量: 401.509
• InChiKey: KOZNAHJIJGCFJJ-SFHVURJKSA-N

物化性质

• 沸点：
  655.4±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  7

制备方法与用途

BMS-442608是一种5-HT1A部分激动剂。

反应信息

• 作为产物：
  描述：

  丁螺环酮 在 Bacillus megaterium cytochrome P₄₅₀ 9-10A-F₈₇A monooxygenase 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 various solvents 为溶剂， 反应 3.0h， 生成 (R)-6'-Hydroxybuspirone
  参考文献：
  名称：

  Enantioselective α-Hydroxylation of 2-Arylacetic Acid Derivatives and Buspirone Catalyzed by Engineered Cytochrome P450 BM-3

  摘要：

  Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspirone, with 99.5% ee.

  DOI：

  10.1021/ja061261x

文献信息

• Preparation of (R)- and (S)-6-hydroxybuspirone by enzymatic resolution or hydroxylation
  作者：Ronald L. Hanson、William L. Parker、David B. Brzozowski、Thomas P. Tully、Mark Liu、Atul Kotnis、Ramesh N. Patel

  DOI：10.1016/j.tetasy.2005.07.020

  日期：2005.8

  buspirone. The (R)- and (S)-enantiomers of 6-hydroxybuspirone were prepared using an enzymatic resolution process. l-Amino acid acylase from Aspergillus melleus (Amano Acylase 30000) was used to hydrolyze racemic 6-acetoxybuspirone to (S)-6-hydroxybuspirone in 95% ee after 45% conversion. The remaining (R)-6-acetoxybuspirone with 88% ee was converted to (R)-6-hydroxybuspirone by acid hydrolysis. The

  6-羟基丁螺环酮是抗焦虑药丁螺环酮的活性代谢产物。使用酶拆分方法制备6-羟基丁螺环酮的（R）-和（S）-对映体。来自米曲霉的1-氨基酸酰基转移酶（Amano酰基转移酶30000）在45％转化后用于将外消旋的6-乙酰氧基丁螺环酮在95％ee中水解为（S）-6-羟基丁螺环酮。通过酸水解将剩余的具有88％ee的（R）-6-乙酰氧基丁螺环酮转化为（R）-6-羟基丁螺环酮。通过结晶为亚稳态多晶型物，两种对映体的ee可以提高到99％。（S还通过使用抗生素链霉菌ATCC 14890对丁螺环酮进行羟基化，以88％ee和14.5％收率获得了-6-羟基丁螺环酮。
• Enantioselective microbial reduction of 6-oxo-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione
  作者：Ramesh Patel、Linda Chu、Venkata Nanduri、Jianqing Li、Atul Kotnis、William Parker、Mark Liu、Richard Mueller

  DOI：10.1016/j.tetasy.2005.07.015

  日期：2005.8

  The enantioselective microbial reduction of 6-oxo-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione 1 to either of the corresponding (R)- or (S)-6-hydroxy-8-[4-[4-(2-pyrimidiiiyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane7,9-diones 2 and 3 is described. (c) 2005 Elsevier Ltd. All rights reserved.
• Enantioselective α-Hydroxylation of 2-Arylacetic Acid Derivatives and Buspirone Catalyzed by Engineered Cytochrome P450 BM-3
  作者：Marco Landwehr、Lisa Hochrein、Christopher R. Otey、Alex Kasrayan、Jan-E. Bäckvall、Frances H. Arnold

  DOI：10.1021/ja061261x

  日期：2006.5.1

  Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspirone, with 99.5% ee.