(1R)-6β-hydroxycineole | 18679-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: (1R)-6β-hydroxycineole
• 英文别名: exo-2-hydroxycineole；2-Exo-hydroxy-1,8-cineole；(1R,4S,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol
• CAS: 18679-48-6；38223-62-0；38223-63-1；54164-88-4；60761-00-4；66965-45-5；92999-78-5；103665-39-0；109009-75-8
• 化学式: C₁₀H₁₈O₂
• 分子量: 170.252
• InChiKey: YVCUGZBVCHODNB-OYNCUSHFSA-N

物化性质

• 沸点：
  238.7±8.0 °C(Predicted)
• 密度：
  1.037±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  (1R)-6β-hydroxycineole 在 selenium(IV) oxide 、 草酰氯 、 对甲苯磺酸 、 二甲基亚砜 作用下， 以 二氯甲烷 、 溶剂黄146 、 甲苯 为溶剂， 反应 12.9h， 生成 (1R)-5-(1,3-dioxolan-2-yl)-6-ketocineole
  参考文献：
  名称：

  Synthesis of oxygenated cineole derivatives from cineole: utility of cytochrome P450cin as an enantioselective catalyst

  摘要：

  The oxidation of cineole to (1R)-6 beta-hydroxycineole by cytochrome P450(cin) (CYP176A) is utilised as the initial step in the synthesis of a range of compounds, both novel and ones previously known only as race-mates. The potential of P450(cin) to provide useful, enantiopure building blocks is thus demonstrated. In particular, hydroxylation by this enzyme was used as the initial step in the synthesis of a range of functionalised cineole derivatives that could be used as mechanistic probes to elucidate the effect of substrate structure on the transformations mediated by P450(cin). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.02.004
• 作为产物：
  描述：

  α-松油醇 在 间氯过氧苯甲酸 作用下， 生成 (1R)-6β-hydroxycineole
  参考文献：
  名称：

  的体内细胞色素P450 CIN（CYP176A1）催化用于代谢物的生产系统

  摘要：

  细胞色素P450 cin（CYP176A1）是一种从Bracii细菌中分离的细菌P450 ，它催化1,8-桉树脑羟基化为（1 R）-6β-羟基桉树脑。P450 cin在体外使用两种氧化还原伴侣进行催化：cindoxin，其生理性含FMN的氧化还原伴侣，以及大肠杆菌黄素毒素还原酶。在这里，我们报告了一个表达P450 cin，cindoxin和E.coli flavodoxin还原酶的三顺反子质粒的构建和一个仅编码P450 cin和cindoxin的双顺反子质粒的构建。大肠杆菌用双顺反子载体转化的草甘膦有效地催化了1,8-桉树脑的氧化，推测其内源性大肠杆菌黄酮毒素还原酶可作为末端电子转移蛋白。该体内系统能够以〜1 g / L培养物的产量产生对映体纯的（1 R）-6β-羟基桉树脑，因此提供了该化合物的简单一步合成。此外，还评估了（1 R）和（1 S）樟脑的代谢，1,8-桉树脑的结构同源物，以研究

  DOI：

  10.1016/j.molcatb.2012.03.007

文献信息

• Cloning, Expression and Purification of Cindoxin, an Unusual Fmn-Containing Cytochrome P450 Redox Partner
  作者：David B. Hawkes、Kate E. Slessor、Paul V. Bernhardt、James J. De Voss

  DOI：10.1002/cbic.201000119

  日期：——

  Living in cin: Cindoxin is an FMN‐containing cytochrome P450 redox partner that mediates the transfer of electrons derived ultimately from NADPH to P450cin, which then catalyses the enantiospecific hydroxylation of cineole. The P450cin/cindoxin system is unique and represents a new cytochrome P450/redox partner class.

  生活在cin中：Cindoxin是一种含FMN的细胞色素P450氧化还原伙伴，它介导最终将NADPH衍生的电子转移至P450 cin，然后催化桉树脑的对映体特异性羟基化。P450 cin / cindoxin系统是独特的，代表了新的细胞色素P450 /氧化还原伴侣类别。
• Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes
  作者：M. Miyazawa、M. Shindo、T. Shimada

  DOI：10.1080/00498250110065595

  日期：2001.1

  involved in the 2-hydroxylation of 1,4-cineole by human liver microsomes, based on the following lines of evidence. First, 1,4-cineole 2-hydroxylation activities catalysed by human liver microsomes were inhibited by ketoconazole, a potent inhibitor of CYP3A activities, and an anti-CYP3A4 antibody. Second, there was a good correlation beteeen CYP3A4 contents and 1,4-cineole 2-hydroxylation activities in

  1.在大鼠和人肝微粒体中研究了1,4-桉树脑（一种单萜环醚）的氧化作用，并在昆虫细胞中表达了重组细胞色素P450（P450或CYP）酶，其中引入了人P450和NADPH-P450还原酶cDNA 。通过气相色谱/质谱分析，确定2-和-exo-hydroxy-1,4-cineole是大鼠和人P450酶催化的1,4-cineole的主要氧化产物。2.根据以下证据，CYP3A4是一种主要的酶，参与人肝微粒体对1，4-桉树脑的2-羟基化反应。首先，人肝微粒体催化的1,4-桉树脑2-羟基化活性被酮康唑（一种有效的CYP3A活性抑制剂）和抗CYP3A4抗体抑制。其次，CYP3A4的含量与1之间存在良好的相关性，检查的十八个人类样本的肝微粒体中的4-cineole 2-羟化活性。最后，在所检查的10种重组人P450酶中，CYP3A4对1,4-桉树脑2-羟基化的活性最高。3.孕烯醇酮16α-腈和地塞米松在大鼠中诱导了肝微粒体1
• Cytochrome P450cin (CYP176A), Isolation, Expression, and Characterization
  作者：David B. Hawkes、Gregory W. Adams、Alma L. Burlingame、Paul R. Ortiz de Montellano、James J. De Voss

  DOI：10.1074/jbc.m203382200

  日期：2002.8

  DNA fragment containing the cytochrome P450(cin) gene (cinA). Sequencing revealed three open reading frames that were identified on the basis of sequence homology as a cytochrome P450, an NADPH-dependent flavodoxin/ferrodoxin reductase, and a flavodoxin. This arrangement suggests that P450(cin) may be the first isolated P450 to use a flavodoxin as its natural redox partner. Sequencing also identified

  细胞色素P450是血蛋白超家族的成员，参与了真核生物和原核生物中各种生理和异种生物化合物的氧化代谢。对细菌P450的研究，特别是涉及单萜氧化的P450的研究，为我们对这些蛋白质的理解提供了不可或缺的贡献，而不再涉及真核生物形式所遇到的问题。我们在这里报告了一种新型的细胞色素P450（P450（cin），CYP176A1），它是从巴西柠檬酸杆菌菌株中纯化的，该菌株能够使用桉树脑1作为其唯一的碳和能量来源。该酶已纯化至均一，并确定了三种胰蛋白酶肽的氨基酸序列。通过使用此信息，开发了基于PCR的克隆策略，该策略允许分离包含细胞色素P450（cin）基因（cinA）的4-kb DNA片段。测序揭示了三个开放阅读框，其根据序列同源性被鉴定为细胞色素P450，NADPH依赖的黄酮毒素/铁氧还蛋白还原酶和黄酮毒素。这种安排表明，P450（cin）可能是第一个使用黄酮毒素作为其天然氧化还原伴侣的分离出的P
• Enantiomeric Purity and Odor Characteristics of 2- and 3-Acetoxy-1,8-cineoles in the Rhizomes of <i>Alpinia </i><i>g</i><i>alanga</i> Willd.
  作者：Kikue Kubota、Yuki Someya、Reiko Yoshida、Akio Kobayashi、Tetsu-ichiro Morita、Hiroyuki Koshino

  DOI：10.1021/jf9807465

  日期：1999.2.1

  (S)-(+)-O-methylmandelate esters of trans- and cis-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-ols (2- and 3-hydroxy-1,8-cineoles) were prepared, and eight diastereomers were separated. The absolute configuration of the asymmetric carbons of the cineole moiety of each diastereomer was determined by H-1 NMR data according to the Mosher theory. Each mandelate was reduced with LiAlHe4 to obtain optically pure hydroxy-1,8-cineoles, this being followed by acetylation to afford optically pure acetoxy-1,8-cineoles. These acetates were subjected to chiral GC, using a cyclodextrin column, and the enantiomeric purity of trans- and cis-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-yl acetates in the aroma concentrate from the rhizomes of Alpinia galanga was determined as 93.9 (5S), 19.4 (5R), 63.5 (6R), and 100 (6R) % cc, respectively. The aroma character of each enantiomer was also evaluated by GC-sniffing.
• Cineole biodegradation: Molecular cloning, expression and characterisation of (1R)-6β-hydroxycineole dehydrogenase from Citrobacter braakii
  作者：Kate E. Slessor、Jeanette E. Stok、Sonia M. Cavaignac、David B. Hawkes、Younes Ghasemi、James J. De Voss

  DOI：10.1016/j.bioorg.2009.12.003

  日期：2010.4

  The first steps in the biodegradation of 1,8-cineole involve the introduction of an alcohol and its subsequent oxidation to a ketone. In Citrobacter braakii, cytochrome P450(cin) has previously been demonstrated to perform the first oxidation to produce (1R)-6 beta-hydroxycineole. In this study, we have cloned cinD from C. braakii and expressed the gene product, which displays significant homology to a number of short-chain alcohol dehydrogenases. It was demonstrated that the gene product of cinD exhibits (1R)-6 beta-hydroxycineole dehydrogenase activity, the second step in the degradation of 1,8-cineole. All four isomers of 6-hydroxycineole were examined but only (1R)-6 beta-hydroxycineole was converted to (1R)-6-ketocineole. The (1R)-6 beta-hydroxycineole dehydrogenase exhibited a strict requirement for NAD(H), with no reaction observed in the presence of NADP(H). The enzyme also catalyses the reverse reaction, reducing (1R)-6-ketocineole to (1R)-6 beta-hydroxycineole. During this study the N-terminal His-tag used to assist protein purification was found to interfere with NAD(H) binding and lower enzyme activity. This could be recovered by the addition of Ni2+ ions or proteolytic removal of the His-tag. (C) 2009 Elsevier Inc. All rights reserved.