Alpha-隐黄素 | 24480-38-4

• 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
• 中文名称: Alpha-隐黄素
• 英文名称: zeinoxanthin
• 英文别名: α-cryptoxanthin；α-kryptoxanthin；all-trans-α-cryptoxanthin；(1R)-3,5,5-trimethyl-4-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16-tetramethyl-18-[(1R)-2,6,6-trimethylcyclohex-2-en-1-yl]octadeca-1,3,5,7,9,11,13,15,17-nonaenyl]cyclohex-3-en-1-ol
• CAS: 24480-38-4
• 化学式: C₄₀H₅₆O
• 分子量: 552.884
• InChiKey: NBZANZVJRKXVBH-NHWXEJKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  氧气 、 1-Deoxy-1-(7,8-dimethyl-2,4-dioxidobenzo[g]pteridin-10(5H)-yl)-5-O-phosphonopentitol 、 Alpha-隐黄素 生成 氢(+1)阳离子 、 水 、 叶黄素 、 FMN
  参考文献：
  名称：

  The Arabidopsis LUT1 locus encodes a member of the cytochrome P450 family that is required for carotenoid ε-ring hydroxylation activity

  摘要：

  叶黄素是一种二羟基黄酮类，是植物光合组织中最丰富的类胡萝卜素，并在光收集复合体中发挥关键的结构和功能作用。类胡萝卜素β-和ε-羟化酶催化α-胡萝卜素（β,ε-胡萝卜素）转化为叶黄素。与已从许多生物体中克隆和表征的β-羟化酶相反，ε-羟化酶仅通过在拟南芥中的lut1突变基因进行遗传定义。我们通过位置克隆分离了LUT1基因，并发现，与所有已知的类胡萝卜素羟化酶不同的是，它是一种细胞色素P450型单加氧酶，CYP97C1。将lut1-3的空突变等位基因引入β-羟化酶1 / β-羟化酶2（b1 b2）双突变体背景中，其中两种拟南芥β-羟化酶均被破坏，得到了一个基因型（lut1-3 b1 b2），其中所有已知的三种类胡萝卜素羟化酶活性被消除。令人惊讶的是，lut1-3 b1 b2中仍产生羟基化的β-环，这表明在体内存在第四种不同于β-羟化酶1或2的未知类胡萝卜素β-羟化酶。CYP97家族的第二个叶绿体定位成员CYP97A3与LUT1相似度为49％，被假设为这种额外的β-环羟化活性的可能候选者。总体而言，LUT1定义了一类独立进化且使用不同机制于非血红素二铁β-羟化酶的类胡萝卜素羟化酶。

  DOI：

  10.1073/pnas.2237237100
• 作为产物：
  描述：

  叶黄素 在 sodium (trifluoroacetoxy)borohydride 、 zinc(II) iodide 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 Alpha-隐黄素 、 3R,3R'-zeaxanthin
  参考文献：
  名称：

  Method for production of rare carotenoids from commercially available lutein

  摘要：

  披露了将(3R,3′R,6′R)-叶黄素转化为(3R,6′R)-α-隐花黄素、(3R)-β-隐花黄素、无水叶黄素I、II和III（叶黄素的脱水产物）的过程，以及一种分离和纯化单个类胡萝卜素的方法，包括未反应的(3R,3′R)-玉米黄质。该发明还包括两种将(3R,3′R,6′R)-叶黄素转化为(3R,6′R)-α-隐花黄素的方法，产率非常高。

  公开号：

  US20030220525A1

文献信息

• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Process For The Preparation of Beta and Alpha Cryptoxanthin
  申请人：KHACHIK Frederick

  公开号：US20100280286A1

  公开（公告）日：2010-11-04

  The present invention relates to a process for converting lutein and/or lutein esters to (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin, suitable for human consumption as dietary supplements, by employing safe and environmentally friendly reagents. (3R)-β-Cryptoxanthin and (3R,6′R)-α-cryptoxanthin are two rare food carotenoids that are not commercially available and the former exhibits vitamin A activity. In the first synthetic step, commercially available lutein and/or lutein esters are transformed into a mixture of dehydration products of lutein (anhydroluteins) in the presence of a catalytic amount of an acid. The resulting anhydroluteins are then converted to (3R)-β-cryptoxanthin (major product) and (3R,6′R)-α-cryptoxanthin (minor product) by heterogeneous catalytic hydrogenation employing transition elements of group VIII (Pt, Pd, Rh supported on alumina or carbon) in a variety of organic solvents under atmospheric pressure of hydrogen and at temperatures ranging from −15° C. to 40° C. Among these catalysts, Pt supported on alumina at 40° C. in ethyl acetate provides the best yield of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin. Several homogeneous catalysts can also promote the regioselective hydrogenation of anhydroluteins to a mixture of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin in low to moderate yields. The catalysts may be transition metal complexes such as palladium acetylacetonate, Rh(Ph 3 P) 3 Cl (Wilkinson's catalyst), [(C 6 H 11 ) 3 P[C 8 H 12 ][C 5 H 5 N] Ir + PF6 − (Crabtree catalyst), or [C 8 H 12 ][(MePh 2 P) 2 ]Ir + PF6 − . Among these, Wilkinson catalyst converts anhydroluteins to (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin in nearly quantitative yield. A novel feature of this invention is the regioselective hydrogenation of anhydroluteins while the highly conjugated polyene chain of these carotenoids remains intact.

  本发明涉及一种将叶黄素和/或叶黄素酯转化为（3R）-β-隐花黄素和（3R,6′R）-α-隐花黄素的过程，适合作为人类膳食补充剂，采用安全且环保的试剂。 （3R）-β-隐花黄素和（3R,6′R）-α-隐花黄素是两种罕见的食品类胡萝卜素，目前商业上不可获得，前者具有维生素A活性。在第一合成步骤中，商业上可获得的叶黄素和/或叶黄素酯在酸的催化下转化为叶黄素的脱水产物混合物（脱水叶黄素）。然后，通过使用过渡元素（Pt、Pd、Rh负载在氧化铝或碳上）在各种有机溶剂中，利用异质催化加氢将得到的脱水叶黄素转化为（3R）-β-隐花黄素（主要产物）和（3R,6′R）-α-隐花黄素（次要产物），在氢气大气压下，温度范围从-15°C到40°C。在这些催化剂中，40°C时在乙酸乙酯中负载Pt提供了（3R）-β-隐花黄素和（3R,6′R）-α-隐花黄素的最佳产率。几种均相催化剂也可以促进叶黄素的区域选择性加氢，将其转化为（3R）-β-隐花黄素和（3R,6′R）-α-隐花黄素的混合物，产率较低至适中。这些催化剂可以是过渡金属配合物，如醋酸钯、Rh(Ph3P)3Cl（威尔金森催化剂）、[(C6H11)3P[C8H12][C5H5N] Ir+PF6−（克拉布特里催化剂）或[C8H12][(MePh2P)2]Ir+PF6−。在这些催化剂中，威尔金森催化剂将脱水叶黄素转化为（3R）-β-隐花黄素和（3R,6′R）-α-隐花黄素，产率接近定量。本发明的一个新特点是在叶黄素的高度共轭多烯链保持完整的情况下对脱水叶黄素进行区域选择性加氢。
• Glucuronidated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014734A1

  公开（公告）日：2007-01-18

  This invention provides glucuronidated nebivolol metabolites and pharmaceutical compositions of glucuronidated nebivolol metabolites for treatment of cardiovascular diseases. In addition, this invention also provides compositions comprising nebivolol and/or at least one glucuronidated metabolite of nebivolol and/or at least one other active compound in a pharmaceutically acceptable carrier. This invention also provides methods of treating and/or preventing vascular diseases, by administering at least one glucuronidated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one glucuronidated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  这项发明提供了葡萄糖醛酸化的尼布ivolol代谢物以及用于治疗心血管疾病的葡萄糖醛酸化的尼布ivolol代谢物的制药组合物。此外，该发明还提供了包含尼布ivolol和/或至少一种尼布ivolol的葡萄糖醛酸化代谢物和/或至少一种其他活性化合物的药用可接受载体的组合物。该发明还提供了通过向受影响血管疾病的靶位点投与至少一种能释放治疗有效量一氧化氮的尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防血管疾病的方法。此外，该发明旨在通过投与至少一种尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防偏头痛。该发明还可与代谢综合征紊乱的单一治疗或联合治疗一起使用。
• [EN] PROCESS FOR THE PREPARATION OF ALPHA- AND BETA-CRYPTOXANTHIN<br/>[FR] PROCESSUS DE PREPARATION D'ALPHA ET DE BETA-CRYPTOXANTHINE
  申请人：UNIV MARYLAND

  公开号：WO2005044769A1

  公开（公告）日：2005-05-19

  The present invention relates to a process for converting lutein and/or lutein esters to β-cryptoxanthin and α-cryptoxanthin, suitable for human consumption as dietary supplements, by employing safe and environmentally friendly reagents. In the first synthetic step, commercially available lutein and/or lutein esters are transformed into a mixture of dehydration products of lutein (anhydroluteins) in the presence of a catalytic amount of an acid. The resulting anhydroluteins are then converted to β-cryptoxanthin (major product) and α-cryptoxanthin (minor product) by heterogeneous catalytic hydrogenation employing transition elements of group VIII in a variety of organic solvents under atmospheric pressure of hydrogen. A novel feature of this invention is the regioselective hydrogenation of anhydroluteins while the highly conjugated polyene chain of these carotenoids remains intact.

  本发明涉及一种将叶黄素和/或叶黄素酯转化为β-隐子黄质和α-隐子黄质的过程，适合作为膳食补充剂供人类消费，采用安全和环保的试剂。在第一合成步骤中，利用商业上可获得的叶黄素和/或叶黄素酯在少量酸的存在下转化为叶黄素的脱水产物混合物（脱水叶黄素）。然后，利用过渡元素群VIII在各种有机溶剂中，在氢气大气压下进行异质催化加氢，将所得的脱水叶黄素转化为β-隐子黄质（主要产物）和α-隐子黄质（次要产物）。本发明的一个新特点是在保持这些类胡萝卜素高度共轭多烯链完整的情况下，对脱水叶黄素进行区域选择性加氢。
• Process for Synthesis of (3R,3'R)-Zeaxanthin and (3R,3'S;meso)-Zeaxanthin from (3R,3'R,6'R)-Lutein via (3R)-3',4'-Anhydrolutein
  申请人：Khachik Frederick

  公开号：US20090238933A1

  公开（公告）日：2009-09-24

  (3R, 3′R, 6′R)-Lutein and (3R, 3′R)-zeaxanthin are two dietary carotenoids that are present in most fruits and vegetables commonly consumed in the US and accumulate in the human plasma, major organs, and ocular tissues. Another stereoisomer of (3R, 3′R)-zeaxanthin that is not of dietary origin but is found in the human ocular tissues is (3R, 3′S; meso)-zeaxanthin. There is growing evidence that these carotenoids play an important role in the prevention of age-related macular degeneration (AMD) that is the leading cause of blindness in the U.S. and the Western World. In view of the potential therapeutic application of dietary lutein, (3R, 3′R)-zeaxanthin, and (3R, 3′S; meso)-zeaxanthin, the industrial production of these carotenoids is of considerable importance. The present invention provides a process for the partial synthesis of (3R, 3′R)-zeaxanthin and (3R, 3′S; meso)-zeaxanthin from a readily accessible dehydration product of (3R, 3′R, 6′R)-lutein, namely, (3R)-3′,4′-didehydro-β,β-caroten-3-ol [(3R)-3′,4′-anhydrolutein]. The process involves regioselective hydroboration of (3R)-3′,4′-anhydrolutein to a mixture of (3R, 3′R)-zeaxanthin and (3R, 3′S; meso)-zeaxanthin followed by separation of these carotenoids by enzyme-mediated acylation.

  (3R, 3′R, 6′R)-叶黄素和(3R, 3′R)-玉米黄质是两种膳食类胡萝卜素，存在于美国常见的大多数水果和蔬菜中，并在人类血浆、主要器官和眼组织中积累。另一种立体异构体(3R, 3′S; meso)-玉米黄质虽非膳食来源，但在人眼组织中发现。越来越多的证据表明，这些类胡萝卜素在预防年龄相关性黄斑变性（AMD）方面发挥重要作用，该病是美国和西方世界导致失明的主要原因。鉴于膳食叶黄素、(3R, 3′R)-玉米黄质和(3R, 3′S; meso)-玉米黄质的潜在治疗应用，这些类胡萝卜素的工业生产具有相当重要的意义。本发明提供了一种从(3R, 3′R, 6′R)-叶黄素的易得脱水产物(3R)-3′,4′-去氢β,β-类胡萝卜烯-3-醇[(3R)-3′,4′-anhydrolutein]部分合成(3R, 3′R)-玉米黄质和(3R, 3′S; meso)-玉米黄质的方法。该过程涉及对(3R)-3′,4′-anhydrolutein的区域选择性氢硼化，得到(3R, 3′R)-玉米黄质和(3R, 3′S; meso)-玉米黄质的混合物，然后通过酶介导的酰化分离这些类胡萝卜素。