α,β-侧柏酮 | 471-15-8

• 物质功能分类: 分析化学 - 对照品
• 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: α,β-侧柏酮
• 中文别名: (-)-1-异丙基-4-甲基双环[3.1.0]己-3-酮
• 英文名称: Thujone
• 英文别名: alpha,beta-Thujone；(1S,5R)-4-methyl-1-propan-2-ylbicyclo[3.1.0]hexan-3-one
• CAS: 471-15-8；546-80-5；1125-12-8；58501-78-3；59573-80-7；69257-13-2；76231-76-0；78821-49-5；116562-18-6；116562-20-0
• 化学式: C₁₀H₁₆O
• 分子量: 152.236
• InChiKey: USMNOWBWPHYOEA-VWHDNNRLSA-N

物化性质

• 熔点：
  181℃
• 比旋光度：
  D20 -19.2°
• 沸点：
  84-86 °C17 mm Hg(lit.)
• 密度：
  0.914 g/mL at 20 °C (lit.)
• 闪点：
  148 °F
• 溶解度：
  DMSO：100 mg/mL（656.90 mM；需要超声波）
• LogP：
  2.044 (est)
• 颜色/状态：
  Colorless or almost colorless liquid
• 蒸汽压力：
  0.449 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions. /Alpha-Thujone/
• 分解：
  Hazardous decomposition products formed under fire conditions. - Carbon oxides. /Alpha-Thujone/

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

这项研究旨在体外研究人肝制剂中alpha-侧柏酮的代谢特性，并确定细胞色素P450（CYP）以及可能的其他催化alpha-侧柏酮生物转化的酶的作用。通过开发一种液相色谱-质谱（LC-MS）方法来测量alpha-侧柏酮和四种潜在代谢物，实验结果表明人肝微粒体产生了两种主要代谢物（7-羟基侧柏酮和4-羟基侧柏酮）和两种次要代谢物（2-羟基侧柏酮和香荆芥酚）。在人肝匀浆中检测到了谷胱甘肽和半胱氨酸结合物，但未进行量化。没有检测到葡萄糖醛酸或硫酸结合物。主要羟基化反应占到了alpha-侧柏酮初级微粒体代谢的90%以上。通过CYP重组酶筛选alpha-侧柏酮的代谢，发现CYP2A6主要负责主要的7-和4-羟基化反应，尽管CYP3A4和CYP2B6参与程度较低，CYP3A4和CYP2B6催化了次要的2-羟基化反应。根据不同重组CYP酶的固有效率和这些酶在人肝微粒体中的平均丰度，计算出CYP2A6是人肝微粒体中最活跃的酶，平均负责70-80%的代谢。抑制作用筛选表明，alpha-侧柏酮抑制了CYP2A6和CYP2B6，50%抑制浓度值分别为15.4和17.5微摩尔。

This study aims to characterize the metabolism of alpha-thujone in human liver preparations in vitro and to identify the role of cytochrome P450 (CYP) and possibly other enzymes catalyzing alpha-thujone biotransformations. With a liquid chromatography-mass spectrometry (LC-MS) method developed for measuring alpha-thujone and four potential metabolites, it was demonstrated that human liver microsomes produced two major (7- and 4-hydroxy-thujone) and two minor (2-hydroxy-thujone and carvacrol) metabolites. Glutathione and cysteine conjugates were detected in human liver homogenates, but not quantified. No glucuronide or sulphate conjugates were detected. Major hydroxylations accounted for more than 90% of the primary microsomal metabolism of alpha-thujone. Screening of alpha-thujone metabolism with CYP recombinant enzymes indicated that CYP2A6 was principally responsible for the major 7- and 4-hydroxylation reactions, although CYP3A4 and CYP2B6 participated to a lesser extent and CYP3A4 and CYP2B6 catalyzed minor 2-hydroxylation. Based on the intrinsic efficiencies of different recombinant CYP enzymes and average abundances of these enzymes in human liver microsomes, CYP2A6 was calculated to be the most active enzyme in human liver microsomes, responsible for 70-80% of the metabolism on average. Inhibition screening indicated that alpha-thujone inhibited both CYP2A6 and CYP2B6, with 50% inhibitory concentration values of 15.4 and 17.5 uM, respectively.

来源:Hazardous Substances Data Bank (HSDB)

代谢

alpha-侧柏酮在小鼠肝脏微粒体和NADPH（细胞色素P450）的作用下迅速体外代谢，主要生成7-羟基-alpha-侧柏酮，并伴有五种次要产物（4-羟基-alpha-侧柏酮、4-羟基-beta-侧柏酮、另外两种羟基侧柏酮以及7,8-脱氢-alpha-侧柏酮），其中一些也在腹腔注射alpha-侧柏酮的小鼠大脑中检测到。主要代谢物7-羟基代谢物在大脑中的浓度远高于alpha-侧柏酮，但对小鼠和果蝇的毒性较低，在结合实验中的效力也较低。其他检测到的代谢物也是解毒产物。因此，在苦艾酒和草药药物中的alpha-侧柏酮是一种快速作用且易于解毒的GABA门控氯离子通道调节剂。

alpha-Thujone is quickly metabolized in vitro by mouse liver microsomes with NADPH (cytochrome P450) forming 7-hydroxy-alpha-thujone as the major product plus five minor ones (4-hydroxy-alpha-thujone, 4-hydroxy-beta-thujone, two other hydroxythujones, and 7,8-dehydro-alpha-thujone), several of which also are detected in the brain of mice treated i.p. with alpha-thujone. The major 7-hydroxy metabolite attains much higher brain levels than alpha-thujone but is less toxic to mice and Drosophila and less potent in the binding assay. The other metabolites assayed are also detoxification products. Thus, alpha-thujone in absinthe and herbal medicines is a rapid-acting and readily detoxified modulator of the GABA-gated chloride channel.

来源:Hazardous Substances Data Bank (HSDB)

代谢

含有alpha-和beta-侧柏酮的精油是重要的草药药物和食品添加剂。侧柏酮对映体是快速代谢的致惊厥剂，作为γ-氨基丁酸门控氯通道的非竞争性阻断剂。合成和分析代谢物是理解它们健康影响的重要步骤。alpha-和beta-侧柏酮作为2,3-烯醇ates与氧化二过氧钼(吡啶)(六甲基磷酰三胺)的氧化得到了相应的(2R)-2-羟基侧柏酮，由(1)H和(13)C NMR以及X射线晶体学确定。Alpha-侧柏酮通过3,4-烯醇醋酸分别与过酸和四氧化锇氧化转化为4-羟基-alpha-和-beta-侧柏酮。臭氧化提供了7-羟基-alpha-和-beta-侧柏酮，通过脱水提供了7,8-脱氢化合物。4,10-脱氢侧柏酮是通过萨宾烯经萨宾醇制备的。羟基和脱氢衍生物可以通过气相色谱/质谱(GC/MS)作为母化合物以及三甲基硅基和甲氧基亚胺衍生物轻松识别和分析。另一项研究建立了所有这些化合物都是alpha-和beta-侧柏酮的代谢物。

Essential oils containing alpha- and beta-thujones are important herbal medicines and food additives. The thujone diastereomers are rapidly metabolized convulsants acting as noncompetitive blockers of the gamma-aminobutyric acid-gated chloride channel. Synthesis and analysis of the metabolites are essential steps in understanding their health effects. Oxidation of alpha- and beta-thujones as their 2,3-enolates with oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) gave the corresponding (2R)-2-hydroxythujones assigned by (1)H and (13)C NMR and X-ray crystallography. Alpha-Thujone was converted to 4-hydroxy-alpha- and -beta-thujones via the 3,4-enol acetate on oxidation with peracid and osmium tetroxide, respectively. Ozonation provided 7-hydroxy-alpha- and -beta-thujones, and by dehydration provided the 7,8-dehydro compounds. 4,10-Dehydrothujone was prepared from sabinene via sabinol. The hydroxy and dehydro derivatives are readily identified and analyzed by GC/MS as the parent compounds and trimethylsilyl and methyloxime derivatives. A separate study established that all of these compounds are metabolites of alpha- and beta-thujones.

来源:Hazardous Substances Data Bank (HSDB)

代谢

洋艾素（thujone）的代谢已经在多种物种的体外和体内研究中得到了阐明，同时在人肝制剂的体外研究中也有所了解。CYP2A6是主要的代谢酶，其次是CYP3A4，在较小程度上还有CYP2B6。与CYP相关的代谢可能会引起一些潜在的药物遗传学和代谢相互作用后果。

Metabolism of thujone has been elucidated both in vitro and in vivo in several species and in vitro in human liver preparations. CYP2A6 is the principal metabolic enzyme, followed by CYP3A4 and, to a lesser extent, CYP2B6. CYP-associated metabolism may give rise to some potential pharmacogenetic and metabolic interaction consequences.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

丁酸（BHA）和双丙酮醇对侧柏酮引起的惊厥的作用在兔子上进行了研究。兔子通过静脉注射（iv）0.4立方厘米（cc）的1%侧柏酮以产生惊厥，随后在5分钟内以每千克（kg）0.5cc BHA的剂量进行iv注射。在BHA治疗后没有观察到效果。双丙酮醇（0.5 cc/kg）在1、5和24小时通过胃管喂养给侧柏酮处理的兔子。在5小时观察到明显的抗惊厥效果，并在24小时减弱。使用50毫克（mg）/kg苯巴比妥钠的类似程序在6小时和24小时显示出明显的抗惊厥效果。500 mg/kg剂量的苯巴比妥钠导致类似昏迷的状态，随后在1小时内进行侧柏酮处理。侧柏酮的惊厥剂量没有效果。作者结论，通过口腔给药的双丙酮醇比苯巴比妥的毒性小得多，但需要更高的剂量才能获得相似的抗惊厥效果。分子中的双丙酮部分具有抗惊厥特性。

The action of beta-hydroxybutyric-acid (BHA) and diacetone-alcohol on thujone induced convulsions was investigated in rabbits. Rabbits were injected intravenously (iv) with 0.4 cubic centimeters (cc) of 1 percent thujone to produce convulsions, followed in 5 minutes by iv injection of 0.5cc BHA per kilogram (kg). No effect was observed after BHA treatment. Diacetone-alcohol (05 cc/kg) was fed by stomach tube to thujone treated rabbits at 1, 5, and 24 hours. A definite anticonvulsant effect was observed at 5 hours and diminished by 24 hours. A similar procedure using 50 milligrams (mg)/kg phenobarbital-sodium showed a definite anticonvulsant effect at 6 hours and at 24 hours. A 500 mg/kg dose of phenobarbital-sodium caused a comatose like state, which was followed in 1 hour by thujone treatment. The thujone convulsing dose had no effect. The author concludes that diacetone-alcohol administered by mouth is much less toxic than phenobarbital but required a higher dose to obtain similar anticonvulsant effect. It is the diacetone part of the molecule that has anticonvulsant properties.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/ 本研究的目的是确定苦艾酒对注意力表现和情绪的影响是否与仅含酒精的饮料不同。导致苦艾酒有毒的成分被认为是侧柏酮。共有25名健康受试者参加了研究。使用了注意力表现测试和两份测试不同情绪维度的问卷。提供了三种含有相同酒精量但含有不同量侧柏酮的饮料。目前的研究结果表明，同时摄入含有高浓度侧柏酮的酒精对注意力表现有负面影响。在这种情况下，受试者倾向于将注意力集中在注意力中心区域的信号上，并忽视外围信号；在注意力外围区域，正确反应的数量显著减少，反应时间和“假警报”反应的数量显著增加。这些效果在第一次测量时最为明显。当受试者受到酒精影响或同时摄入酒精和低浓度侧柏酮时，这些效果并未观察到。情绪状态维度的评估表明，酒精的镇静作用被高浓度的侧柏酮暂时抵消。由于它们显然与酒精的效果相反，这里观察到的反应可以由侧柏酮对γ-氨基丁酸受体的拮抗作用来解释。在检查的其他情绪状态维度中也观察到了类似的改变。

/HUMAN EXPOSURE STUDIES/ The aim of this study was to determine whether the impacts of absinthe on attention performance and mood were different from those experienced with beverages that contain only alcohol. The ingredient causing absinthe's toxicity is believed to be thujone. A total of 25 healthy subjects participated in the study. An attention performance test and two questionnaires testing different mood dimensions were used. Three drinks with an identical amount of alcohol but with different amounts of thujone were offered. The results of the present study showed that the simultaneous administration of alcohol containing a high concentration of thujone had a negative effect on attention performance. Under this condition, the subjects tended to direct their attention to signals in the central field of attention and to neglect peripheral signals; the number of correct reactions decreased significantly in the peripheral field of attention, and reaction time and the number of "false alarm" reactions increased significantly. The effects were most prominent at the time of the first measurement. When the subjects were under the influence of alcohol or were administered both alcohol and a low thujone concentration, these effects were not observed. The assessment of mood state dimensions showed that the anxiolytic effect of alcohol was temporarily counteracted by a high thujone concentration. As they are apparently opposed to the effect of alcohol, the reactions observed here can be explained by the antagonistic effect of thujone on the gamma-aminobutyric acid receptor. Similar alterations were observed for the other mood state dimensions examined.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S23,S26,S36/37/39,S45
• 危险类别码：
  R23/24/25,R36/37/38,R42/43
• 危险品运输编号：
  UN 2810 6.1/PG 3

制备方法与用途

用途

侧柏酮能够作用于大脑中的GABA受体和5-HT3受体。许多国家都对食物或饮料中侧柏酮的含量进行了限制。除了天然存在的(−)-α-侧柏酮和(+)β-侧柏酮外，理论上还存在另外两个对映体形式：(+)-α-侧柏酮和(−)β-侧柏酮。

用途

α-侧柏酮是一种GABA调节剂和遗传毒性化合物，曾在发展中国家的传统药物植物中被发现。

生物活性

α-侧柏酮（α-Thujone）是从西方金钟柏精油中分离出来的单萜类物质，并具有显著的抗肿瘤活性。它作为GABAA受体的可逆调节剂，在抑制GABA诱导的电流时，IC50值为21 μM。α-侧柏酮能诱导依赖于ROS的细胞毒性作用，还能引发细胞凋亡和自噬过程。此外，α-侧柏酮还表现出抗伤害、杀虫及驱虫的效果，并且能够轻松穿透血脑屏障。

反应信息

• 作为反应物：
  描述：

  α,β-侧柏酮 在 氢氧化钾 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 5.5h， 生成 (一)-宁酮
  参考文献：
  名称：

  Epimerisierung von（-）-thujon zu（+）-thujon

  摘要：

  （-）-丁香酮在4-羟甲基丁香酮和丁香酮-4-羧酸上定量异构化为（+）-丁香酮。

  DOI：

  10.1016/s0040-4039(00)71182-8
• 作为产物：
  描述：

  (+)-1-isopropylbicyclo[3.1.0]hexan-3-one 、 碘甲烷 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 12.33h， 生成 α,β-侧柏酮
  参考文献：
  名称：

  NaNO2/HCl 选择性裂解环烷酮的 C-C 键

  摘要：

  建立了一种新型的 NaNO 2 /HCl选择性裂解环烷酮的方法。C-C 键裂解反应在温和条件下顺利进行，选择性地提供通用的酮酸或肟酸。该方法可以简化从现成的原料中合成有价值的手性分子和异香豆素的过程。

  DOI：

  10.1021/acs.orglett.1c02327

文献信息

• Catalytic Asymmetric Synthesis of Cyclohexanes by Hydrogen Borrowing Annulations
  作者：Roly J. Armstrong、Wasim M. Akhtar、Tom A. Young、Fernanda Duarte、Timothy J. Donohoe

  DOI：10.1002/anie.201907514

  日期：2019.9.2

  Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5‐diols via hydrogen

  氢借位催化是烯醇化烷基化的有力替代方法，可将酮与未活化的醇直接偶联。然而，迄今为止，仍无法控制这种方法的绝对立体化学结果的方法。在这里，我们报告了一种通过氢借位催化从1,5-二醇合成对映体富集的环己烷的催化不对称方法。该反应是通过添加手性铱（I）络合物来介导的，该络合物能够在该过程中赋予高水平的对映选择性。已经制备了一系列对映体富集的环己烷，并且通过结合实验和DFT研究探索了对映体诱导的模式。
• Stereoselective Synthesis of Cyclohexanes via an Iridium Catalyzed (5 + 1) Annulation Strategy
  作者：Wasim M. Akhtar、Roly J. Armstrong、James R. Frost、Neil G. Stevenson、Timothy J. Donohoe

  DOI：10.1021/jacs.8b07776

  日期：2018.9.26

  An iridium catalyzed method for the synthesis of functionalized cyclohexanes from methyl ketones and 1,5-diols is described. This process operates by two sequential hydrogen borrowing reactions, providing direct access to multisubstituted cyclic products with high levels of stereocontrol. This methodology represents a novel (5 + 1) strategy for the stereoselective construction of the cyclohexane core

  描述了一种由甲基酮和 1,5-二醇合成官能化环己烷的铱催化方法。该过程通过两个连续的借氢反应进行，可直接获得具有高度立体控制的多取代环状产物。这种方法代表了一种新颖的 (5 + 1) 策略，用于环己烷核心的立体选择性构建。
• Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach
  作者：Roly J. Armstrong、Wasim M. Akhtar、James R. Frost、Kirsten E. Christensen、Neil G. Stevenson、Timothy J. Donohoe

  DOI：10.1016/j.tet.2019.130680

  日期：2019.11

  A highly diastereoselective annulation strategy for the synthesis of alicyclic ketones from diols and pentamethylacetophenone is described. This process is mediated by a commercially available iridium(III) catalyst, and provides efficient access to a wide range of cyclopentane and cyclohexane products with high levels of stereoselectivity. The origins of diastereoselectivity in the annulation reaction

  描述了一种由二醇和五甲基苯乙酮合成脂环族酮的高度非对映选择性环化策略。该方法由可商购的铱（III）催化剂介导，可有效地获得各种具有高立体选择性的环戊烷和环己烷产品。通过一系列控制实验探索了环空反应中非对映选择性的起源，这为如何控制新锻造环周围的每个立体中心提供了解释。
• Synergistic Catalysis: Metal/Proton-Catalyzed Cyclization of Alkynones Toward Bicyclo[3.<i>n</i>.1]alkanones
  作者：Shifa Zhu、Qiaohui Zhang、Kai Chen、Huanfeng Jiang

  DOI：10.1002/anie.201504964

  日期：2015.8.3

  highly efficient and practical synergistically metal/proton‐catalyzed Conia–ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, α,β‐thujone, and 5α‐cholestan‐3‐one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles

  已开发出一种高效且实用的协同金属/质子催化的Conia-ene反应合成双环[3.n.1]烷酮。这种协同催化作用已成功用于修饰天然化合物，例如二氢茉莉酮酸甲酯，α，β-thujone和5α-cholestan-3-one。此外，亲核试剂很容易攻击双环[3.2.1]链烷酮的桥连羰基，从而以优异的收率得到开环的环庚烯酮产物或双环[4.2.1]酰胺。这些反应提供了从简单的起始原料或天然存在的化合物快速进入各种环状结构的途径。
• The absolute configuration of thujane
  作者：G. Ohloff、G. Uhde、A.F. Thomas、E.sz. Kováts

  DOI：10.1016/0040-4020(66)80132-1

  日期：1966.1

  (+)-cis- and (+)-trans-Thujane (XIV and XV) have been correlated with (+)-pulegone (IX) via (+)-pulegene (XIII). Using stereospecific reactions, the hydrocarbons of the thujane series have been linked with their oxygenated members. The absolute configurations found by Norin for these substances are in accord with our findings.

  （+）-顺式-和（+）-反-金钟柏（XIV和XV）已通过（+）-pulegene（XIII）与（+）-pulegone（IX）相关。使用立体定向反应，金钟柏系列的烃已与它们的氧化成员相连。Norin对这些物质发现的绝对构型与我们的发现相符。