3-hydroxy-α-ionone

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3-hydroxy-α-ionone
• 英文别名: 3-Hydroxy-alpha-ionone；(E)-4-(4-hydroxy-2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one
• 化学式: C₁₃H₂₀O₂
• 分子量: 208.301
• InChiKey: FDSNVAKZRJLMJN-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-hydroxy-α-ionone 在 immobilized lipase PS (pseudomonas cepacia) 1,2-环氧丁烷 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 3.5h， 生成 隐黄质
  参考文献：
  名称：

  Process or synthesis of (3S)- and (3R)-3-hydroxy-beta-ionone, and their transformation to zeaxanthin and beta-cryptoxanthin

  摘要：

  本文披露了一种从商业可获得的（rac）-α-离子酮合成（3R）-3-羟基-β-离子酮及其（3S）对映体的高光学纯度的过程。合成这些羟基离子酮的关键中间体是从（rac）-α-离子酮制备的3-酮-α-离子酮缩酮，经过将该酮保护为1,3-二氧杂环后得到。还原3-酮-α-离子酮缩酮，然后去保护，得到3-羟基-α-离子酮，通过碱催化的双键异构化，从（rac）-α-离子酮中总产率为46%转化为（rac）-3-羟基-β-离子酮。这些羟基离子酮的混合物随后通过酶介导的酰化在96%的ee下分离。（3R）-3-羟基-β-离子酮及其（3S）对映体分别按照已知程序转化为（3R）-3-羟基-(β-离子基乙基)三苯基膦盐[(3R)-C15-Wittig盐]和其（3S）对映体[(3S)-C15-Wittig盐]。将这些Wittig盐与商业可获得的2,5-二甲基辛二烯-1,8-二醛进行双Wittig缩合，得到所有3种类脂黄素的立体异构体。类似地，（3R）-C15-Wittig及其（3S）对映体分别与β-脱氧-12'-类胡萝卜素醛偶联。

  公开号：

  US08222458B2
• 作为产物：
  描述：

  alpha-ionone 在 双氧水 、 unspecific peroxygenase (isoform II) from Agrocybe aegerita TM-A₁ 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.5h， 以93%的产率得到3-hydroxy-α-ionone
  参考文献：
  名称：

  真菌过氧化酶对离子和大马士革的选择性加氧。

  摘要：

  角鲨烯类化合物是最有价值的香料成分之一，也被视为合成的基础材料。这项工作显示了来自几种真菌的非特异性过氧化酶（UPOs，EC1.11.2.1）催化α-和β-紫罗兰酮和α-和β-大马康糖酮的氧化官能化的能力。酶促反应产生含氧产物，例如羟基，氧代，羧基和环氧衍生物，它们是调味品，香料和制药工业中令人感兴趣的化合物。尽管根据底物和酶观察到不同的区域选择性，但氧优先在环的烯丙基位置产生，这在与α-紫罗兰酮的反应中特别明显，形成3-羟基-α-紫罗兰酮和/或3-氧代- α-紫罗兰酮。值得注意的是与大马士革的反应，

  DOI：

  10.1021/acs.jafc.0c01019

文献信息

• Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope
  作者：Aélig Robin、Valentin Köhler、Alison Jones、Afruja Ali、Paul P Kelly、Elaine O'Reilly、Nicholas J Turner、Sabine L Flitsch

  DOI：10.3762/bjoc.7.173

  日期：——

  A high-throughput screening protocol for evaluating chimeric, self-sufficient P450 biocatalysts and their mutants against a panel of substrates was developed, leading to the identification of a number of novel biooxidation activities.

  开发了一种高通量筛选方案，用于评估嵌合的、自给自足的 P450 生物催化剂及其针对一组底物的突变体，从而确定了许多新的生物氧化活性。
• Characterization of CYP154F1 from<i>Thermobifida fusca</i>YX and Extension of Its Substrate Spectrum by Site-Directed Mutagenesis
  作者：Ansgar Rühlmann、Georg Groth、Vlada B. Urlacher

  DOI：10.1002/cbic.201700565

  日期：2018.3.2

  Scope determination: Key residues accounting for different activities of CYP154F1 and its thoroughly characterized relative CYP154F1 were identified based on a structural alignment of their homology models. Subsequently, site‐directed mutagenesis was applied to extend the substrate spectrum of CYP154F1 and increase its activity.

  范围的确定：根据CYP154F1的同源性模型的结构比对，确定了CYP154F1不同活性的关键残基及其充分表征的相对CYP154F1。随后，应用定点诱变来扩展CYP154F1的底物谱并增加其活性。
• Process for Synthesis of (3S)- and (3R)-3-Hydroxy-Beta-Ionone, and Their Transformation to Zeaxanthin and Beta-Cryptoxanthin
  申请人：Khachik Frederick

  公开号：US20090311761A1

  公开（公告）日：2009-12-17

  (3R)-3-Hydroxy-β-ionone and (3S)-3-hydroxy-β-ionone are two important intermediates in the synthesis of carotenoids with β-end group such as lutein, zeaxanthin, β-cryptoxanthin, and their stereoisomers. Among the various stereoisomers of these carotenoids, only (3R,3′R,6′R)-lutein, (3R,3′R)-zeaxanthin, and (3R)-β-cryptoxanthin are present in commonly consumed fruits and vegetables. There are 3 possible stereoisomers for zeaxanthin, these are: dietary (3R,3′R)-zeaxanthin (1), non-dietary (3S,3′S)-zeaxanthin (2), and non-dietary (3R,3′S;meso)-zeaxanthin (3) which is a presumed metabolite of dietary lutein. Dietary lutein as well as 1 and 3 are accumulated in the human macula and have been implicated in the prevention of age-related macular degeneration. (3R)-β-Cryptoxanthin (4) is also present in selected ocular tissues at a very low concentration whereas its enantiomer (3S)-β-cryptoxanthin (5) is absent in foods and human plasma. The present invention relates to a process for the synthesis of (3R)-3-hydroxy-β-ionone and its (3S)-enantiomer in high optical purity from commercially available (rac)-α-ionone. The key intermediate for the synthesis of these hydroxyionones is 3-keto-α-ionone ketal that was prepared from (rac)-α-ionone after protection of this ketone as a 1,3-dioxolane. Reduction of 3-keto-α-ionone ketal followed by deprotection, lead to 3-hydroxy-α-ionone that was transformed into (rac)-3-hydroxy-β-ionone by base-catalyzed double bond isomerization in 46% overall yield from (rac)-α-ionone. The racemic mixture of these hydroxyionones was then resolved by enzyme-mediated acylation in 96% ee. (3R)-3-Hydroxy-β-ionone and its (3S)-enantiomer were respectively transformed to (3R)-3-hydroxy-(β-ionylideneethyl)triphenylphosphonium chloride [(3R)—C 15 -Wittig salt] and its (3S)-enantiomer [(3S)—C 15 -Wittig salt] according to known procedures. Double Wittig condensation of these Wittig salts with commercially available 2,5-dimethylocta-2,4,6-triene-1,8-dial provided all 3 stereoisomers of zeaxanthin (1-3). Similarly, (3R)—C 15 -Wittig and its (3S)-enantiomer were each coupled with β-apo-12′-carotenal to yield 4 and 5.

  (3R)-3-羟基-β-离子酮和(3S)-3-羟基-β-离子酮是合成带有β末端基团的类胡萝卜素如叶黄素、玉米黄质、β-隐黄素及其立体异构体的两个重要中间体。在这些类胡萝卜素的各种立体异构体中，只有(3R,3′R,6′R)-叶黄素、(3R,3′R)-玉米黄质和(3R)-β-隐黄素存在于常见的水果和蔬菜中。玉米黄质有3种可能的立体异构体，分别是：膳食(3R,3′R)-玉米黄质（1）、非膳食(3S,3′S)-玉米黄质（2）和非膳食(3R,3′S;meso)-玉米黄质（3），后者被认为是膳食叶黄素的代谢产物。膳食叶黄素以及1和3在人类黄斑中积累，并被认为有助于预防年龄相关性黄斑变性。 (3R)-β-隐黄素（4）也以极低浓度存在于选定的眼部组织中，而其对映异构体(3S)-β-隐黄素（5）在食物和人类血浆中不存在。本发明涉及一种从市售的（rac）-α-离子酮合成（3R）-3-羟基-β-离子酮及其（3S）对映体的高光学纯度的过程。合成这些羟基酮的关键中间体是从（rac）-α-离子酮制备的3-酮-α-离子酮缩酮，在保护该酮为1,3-二氧兰后得到。随后对3-酮-α-离子酮缩酮进行还原和去保护，得到3-羟基-α-离子酮，再经碱催化的双键异构化，从（rac）-α-离子酮中总产率为46%地转化为（rac）-3-羟基-β-离子酮。然后通过酶介导的酰化将这些羟基酮的外消旋混合物在96%纯度下分离。 (3R)-3-羟基-β-离子酮及其（3S）对映体分别按照已知程序转化为(3R)-3-羟基-(β-离子乙基)三苯基膦盐[(3R)—C15-Wittig盐]和其（3S）对映体[(3S)—C15-Wittig盐]。这些Wittig盐与市售的2,5-二甲基辛-2,4,6-三烯-1,8-二醛进行双Wittig缩合，提供了叶黄素的3种立体异构体（1-3）。类似地，(3R)—C15-Wittig及其（3S）对映体分别与β-脱氧-12'-类胡萝卜醛偶联，得到4和5。
• Synthesis of (3S)- and (3R)-3-Hydroxy-β-ionone and Their Transformation into (3S)- and (3R)-β-Cryptoxanthin
  作者：Frederick Khachik、An-Ni Chang

  DOI：10.1055/s-0030-1258382

  日期：2011.2

  (3R)-3-Hydroxy-β-ionone and (3S)-3-hydroxy-β-ionone were synthesized in high enantiomeric purity from commercially available (±)-α-ionone. These ionones were then transformed into (3R)-β-cryptoxanthin and (3S)-β-cryptoxanthin by a C15+C10+C15 Wittig coupling strategy according to known methods. This methodology can considerably simplify the total synthesis of optically active carotenoids with 3-hydroxy-β-end

  （3R）-3-羟基-β-紫罗兰酮和（3S）-3-羟基-β-紫罗兰酮由对映体纯度高的市售（±）-α-紫罗兰酮合成。然后根据已知方法通过C 15 + C 10 + C 15 Wittig偶联策略将这些紫罗兰酮转化为（3 R）-β-隐黄质和（3 S）-β-隐黄质。这种方法可以极大地简化具有3-羟基-β-端基的旋光性类胡萝卜素的总合成，所述基团具有明显的生物活性。 羟基类胡萝卜素-类胡萝卜素前体-手性拆分-立体选择性合成-Wittig反应
• The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from Bacillus subtilis
  作者：Aili Zhang、Ting Zhang、Emma A. Hall、Sean Hutchinson、Max J. Cryle、Luet-Lok Wong、Weihong Zhou、Stephen G. Bell

  DOI：10.1039/c4mb00665h

  日期：——

  The structure of CYP109B1 fromBacillus subtilis, which catalyses the oxidation of ionones, has been determined. This will allow the future design of more efficient biocatalytic monooxygenase systems.

  来自枯草芽孢杆菌的CYP109B1的结构已经确定，它催化离子酮的氧化。这将有助于未来设计更高效的生物催化单加氧酶系统。