(3E)-4-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)but-3-en-2-one | 14398-35-7

• 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: (3E)-4-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)but-3-en-2-one
• 英文别名: (3E)-4-(2,6,6-trimethyl-1,3-cyclohexadien-1-yl)-3-buten-2-one；2,6,6-trimethyl-1-(3-oxo-1-butenyl)-1,3-cyclohexadiene；3,4-didehydro-β-ionone；3,4-Didehydro-β-jonon；3,4-dehydro-β-ionone；3-dehydro-β-ionone；4-(2,6,6-Trimethylcyclohexa-1,3-dienyl)but-3-en-2-one；(E)-4-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)but-3-en-2-one
• CAS: 14398-35-7
• 化学式: C₁₃H₁₈O
• 分子量: 190.285
• InChiKey: UWWCASOGCPOGJP-BQYQJAHWSA-N

物化性质

• 沸点：
  288.8±9.0 °C(Predicted)
• 密度：
  0.966±0.06 g/cm3(Predicted)
• 保留指数：
  1460

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (3E)-4-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)but-3-en-2-one 在 bis-triphenylphosphine-palladium(II) chloride 、 三正丁基氢锡 、 氯化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 脱氢二氢-β-紫罗兰酮
  参考文献：
  名称：

  合成，嗅觉评价和3,4-Didehydroionone立体异构体的绝对构型的确定。

  摘要：

  3,4-二氢二氢紫罗兰酮异构体4，（+）- 6和（-）- 6的合成以及3,4-二氢二氢-7,8-二氢紫罗兰酮异构体5，（+）- 7和（-）-的合成从可商购的外消旋α-紫罗兰酮（1）开始完成图7。它们的外消旋形式制备4 - 7首先被平均的一些化疗和区域选择性反应（的实现方案1和2）。对映体和非对映体选择性脂肪酶介导的4-羟基-γ-紫罗兰酮的动力学乙酰化（10a / 10b）提供4-羟基-γ-紫罗兰酮（+）- 10a /（±）-10b和（+）-4-（乙酰氧基）-γ-紫罗兰酮（（+）12b）（方案3）。后一种化合物用作制备3,4-didehydro- γ-紫罗兰酮（+）-和（-）- 6和3,4-didehydro-7,8- dihydro - γ-紫罗兰酮（+）的原料-和（-）- 7为对映异构体富集形式。（+）- 12b的绝对构型是通过与（+）-（6 S）-γ-紫罗兰酮（（+）- 3）和（-）-（6

  DOI：

  10.1002/hlca.200690109
• 作为产物：
  描述：

  在 Py*HClCrO₃ 、 sodium methylate 、 叔丁醇 作用下， 生成 (3E)-4-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)but-3-en-2-one
  参考文献：
  名称：

  来自环辛基苯硫醚的脂环萜类化合物。六、β-紫罗兰酮衍生物的合成

  摘要：

  4-(2,6,6-Trimethyl-3-oxo-1-cyclohexenyl)-3-buten-2-one 和 4-(2,6,6-trimethyl-1,3-cyclohexadienyl)-3-buten-通过2,4,4-三甲基-3-(苯磺酰基甲基)-2-环己烯-1-醇和1-(苯磺酰基甲基)-2,6,6-三甲基-1,3-环己二烯的烷基化高效合成2-一分别用环氧丙烷氧化和消除磺酰基。

  DOI：

  10.1246/bcsj.51.949

文献信息

• Carotenoids and Related Polyenes, Part 12 First Total Synthesis and Absolute Configuration of 3'-Deoxycapsanthin and 3,4-Didehydroxy-3'-deoxycapsanthin
  作者：Yumiko Yamano、Mahankhali Venu Chary、Akimori Wada

  DOI：10.1248/cpb.58.1362

  日期：——

  The synthesis of 3'-deoxycapsanthin (1) and 3,4-didehydroxy-3'-deoxycapsanthin (2), carotenoids of paprika, has been achieved by employing Lewis acid-promoted regio- and stereoselective rearrangement of the C(15)-epoxy dienal 5a. The absolute stereochemistry of the newly formed C-5 chiral center of rearrangement product 6a was determined to be (R) from its alternative synthesis derived from (+)-(R)-camphonanic

  辣椒粉的类胡萝卜素3'-脱氧辣椒素（1）和3,4-didehydroxy-3'-脱氧辣椒素（2）的合成已通过路易斯酸促进C（15）-的区域和立体选择性重排而实现环氧二烯5a。从其衍生自（+）-（R）-松香酸（11）的替代合成中，确定了新形成的重排产物6a的C-5手性中心的绝对立体化学为（R）。
• Synthesis and in vitro characterization of ionone-based compounds as dual inhibitors of the androgen receptor and NF-κB
  作者：Weiguo Liu、Jinming Zhou、Guoyan Geng、Rongtuan Lin、Jian Hui Wu

  DOI：10.1007/s10637-013-0040-y

  日期：2014.4

  Current therapeutic strategy for advanced prostate cancer is to suppress the androgen receptor (AR) signaling. However, lethal castration-resistant prostate cancer (CRPC) arises due to AR reactivation via multiple mechanisms, including mutations in the AR and cross-talk with other pathways such as NF-κB. We have previously identified two ionone-based antiandrogens (SC97 and SC245), which are full antagonists of the wild type and the clinically-relevant T877A, W741C and H874Y mutated ARs. Here, we discovered SC97 and SC245 also inhibit NF-κB. By synthesizing a series of derivatives of these two compounds, we have discovered a novel compound 3b that potently inhibits both AR and NF-κB signalling, including the AR F876L mutant. Compound 3b showed low micromolar antiproliferative activites in C4-2B and 22Rv1 cells, which express mutated ARs and are androgen-independent, as well as DU-145 and PC-3 cells, which exhibit constitutively activated NF-κB signalling. Our studies indicate 3b is effective against the CRPC cells.

  目前晚期前列腺癌的治疗策略是抑制雄激素受体（AR）信号通路。然而，由于AR通过多种机制的再激活，包括AR的突变和与其他通路如NF-κB的交叉作用，致命的去势抵抗性前列腺癌（CRPC）应运而生。我们之前已识别出两种基于伊诺烯的抗雄激素（SC97和SC245），它们是野生型和临床相关的T877A、W741C和H874Y突变AR的完全拮抗剂。在这里，我们发现SC97和SC245也能抑制NF-κB。通过合成这两种化合物的一系列衍生物，我们发现了一种新化合物3b，能够有效抑制AR和NF-κB信号，包括AR F876L突变体。化合物3b在表达突变AR并具雄激素独立性的C4-2B和22Rv1细胞，以及表现为持续激活的NF-κB信号的DU-145和PC-3细胞中显示出低微摩尔的抗增殖活性。我们的研究表明3b对CRPC细胞有效。
• 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。
• Palladium-catalyzed oxaspirocyclizations
  作者：Pher G. Andersson、Ylva I.M. Nilsson、Jan-E. Bäckvall

  DOI：10.1016/s0040-4020(01)80776-6

  日期：1994.1

  (π-allyl)palladium intermediate, which is attacked by an acetate or a chloride nucleophile leading to an overall 1,4-addition across the diene. The intermediate (π-allyl) palladium complex was independently prepared and characterized. The stereochemistry of the 1,4-addition can be controlled to give either cis or trans 1,4-addition across the double bonds. The oxaspirocyclization was applied to the total

  1-（3-羟烷基）和1-（4-羟烷基）-1,3-环链二烯的钯催化氧化导致立体控制的氧螺环环化。该反应通过螺环（π-烯丙基）钯中间体进行，该中间体被乙酸盐或氯化物亲核试剂攻击，导致整个二烯上的整个1，4-加成。中间体（π-烯丙基）钯配合物是独立制备和表征的。可以控制1，4-加成的立体化学以产生双键上的顺式或反式1，4-加成。oxaspiro环化被应用于theaspirone的全合成。
• Bromination and sulfenylation of polyenone hydrazones
  作者：Albert Feuerer、Theodor Severin

  DOI：10.1016/s0040-4039(00)60356-8

  日期：1993.3

  Ethoxycarbonylhydrazones of dienones are brominated and sulfenylated at the δ-position. Reduction with borohydride and subsequent hydrolysis lead to a 1,5-transposition of the carbonyl group.

  二烯酮的乙氧羰基hydr酮在δ位被溴化和亚磺酰化。用硼氢化物还原并随后水解导致羰基的1，5-移位。

表征谱图