角鲨烯 | 111-02-4

• 物质功能分类: 天然产物 - 萜类
• 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: 角鲨烯
• 中文别名: 2,6,10,15,19,23－六甲基－2,6,10,14,18,22－二十四碳六烯；反式角鲨烯；三十六碳六烯；全反-2,6,10,15,19,23-六甲基-2,6,10,14,18,22-廿四碳六烯
• 英文名称: 2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
• 英文别名: Squalene；supraene；trans-squalene；(6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene；spinacene
• CAS: 111-02-4
• 化学式: C₃₀H₅₀
• 分子量: 410.727
• InChiKey: YYGNTYWPHWGJRM-AAJYLUCBSA-N

物化性质

• 熔点：
  −75 °C(lit.)
• 沸点：
  285 °C25 mm Hg(lit.)
• 密度：
  0.858 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 溶解度：
  DMSO：16.67 mg/mL（40.59 mM；需要超声波）H2O：< 0.1 mg/mL（不溶）
• LogP：
  14.12 at 24℃
• 物理描述：
  Trans-squalene is a clear, slightly yellow liquid with a faint odor. Density 0.858 g / cm3.
• 颜色/状态：
  Oil; crystals from ether/methanol (-5 °C)
• 气味：
  Faint agreeable odor
• 蒸汽压力：
  6.3X10-6 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Stable under recommended storage conditions.

• 分解：
  When heated to decomposition it emits acrid smoke and irritating vapors.
• 粘度：
  12 cP at 25 °C
• 表面张力：
  33.9 mN/m at 22 °C (100 g/L)
• 折光率：
  Index of Refraction: 1.4990 at 20 °C
• 碰撞截面：
  210.9 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]
• 保留指数：
  2808

计算性质

• 辛醇/水分配系数(LogP)：
  11.6
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

提出对角鲨烯的氧化进行综述，角鲨烯是一种由皮脂腺产生的人体特定化合物。这种化学转化在各个层面上引发重要的后果。角鲨烯的副产品，主要是过氧化形式，会导致粉刺的形成，促进炎性痤疮的发展，并可能改变皮肤的纹理（皱纹）。揭示了氧化和/或光氧化机制的实验条件，这表明它们可能是大气污染对皮肤影响的生物标志。臭氧、长波UVA辐射、香烟烟雾等被显示为角鲨烯的强氧化剂。提出了一些体外、离体和体内的测试示例，旨在研究能够促进或对抗这些化学变化的成分或产品，这些变化总体上对各种皮肤部位产生不利影响。

A review of the oxidization of squalene, a specific human compound produced by the sebaceous gland, is proposed. Such chemical transformation induces important consequences at various levels. Squalene by-products, mostly under peroxidized forms, lead to comedogenesis, contribute to the development of inflammatory acne and possibly modify the skin relief (wrinkling). Experimental conditions of oxidation and/or photo-oxidation mechanisms are exposed, suggesting that they could possibly be bio-markers of atmospheric pollution upon skin. Ozone, long UVA rays, cigarette smoke ... are shown powerful oxidizing agents of squalene. Some in vitro, ex vivo and in vivo testings are proposed as examples, aiming at studying ingredients or products capable of boosting or counteracting such chemical changes that, globally, bring adverse effects to various cutaneous compartments.

来源:Hazardous Substances Data Bank (HSDB)

代谢

这项研究使用了质子转移反应-质谱法（PTR-MS）来直接分析臭氧与人类皮肤脂质反应产生的挥发性产物。最初的一系列小规模体外和体内实验之后，进行了模拟办公室环境下的真人实验。后者使用的是现实的臭氧混合比（大约15 ppb，有人在场）。检测到的产物包括含有羰基、羧基或α-羟基酮基的单功能和双功能化合物。在这些产物中，已经鉴定出三种以前未报告过的二羰基化合物，并且暂时鉴定出两种以前未报告过的α-羟基酮。在本研究中检测到的化合物（除丙酮外）在室内污染物调查中被忽略了，这反映了通常用于监测室内空气的分析方法的局限性。结果与臭氧与角鲨烯反应的克里格机制完全一致，角鲨烯是皮肤脂质中最丰富的单一不饱和成分，以及几种不饱和脂肪酸基团在自由或酯化形式。定量产物分析证实，角鲨烯是室内空气与人类表皮界面处臭氧的主要清除剂。臭氧与人类皮肤脂质的反应减少了室内空气中臭氧的混合比，但同时也增加了挥发性产物的混合比，以及假定皮肤表面较少挥发性产物的浓度。一些挥发性产物，尤其是二羰基化合物，可能是呼吸刺激物。一些较少挥发性产物可能是皮肤刺激物。

This study has used proton transfer reaction-mass spectrometry (PTR-MS) for direct air analyses of volatile products resulting from the reactions of ozone with human skin lipids. An initial series of small-scale in vitro and in vivo experiments were followed by experiments conducted with human subjects in a simulated office. The latter were conducted using realistic ozone mixing ratios (approximately 15 ppb with occupants present). Detected products included mono- and bifunctional compounds that contain carbonyl, carboxyl, or alpha-hydroxy ketone groups. Among these, three previously unreported dicarbonyls have been identified, and two previously unreported alpha-hydroxy ketones have been tentatively identified. The compounds detected in this study (excepting acetone) have been overlooked in surveys of indoor pollutants, reflecting the limitations of the analytical methods routinely used to monitor indoor air. The results are fully consistent with the Criegee mechanism for ozone reacting with squalene, the single most abundant unsaturated constituent of skin lipids, and several unsaturated fatty acid moieties in their free or esterified forms. Quantitative product analysis confirms that squalene is the major scavenger of ozone at the interface between room air and the human envelope. Reactions between ozone and human skin lipids reduce the mixing ratio of ozone in indoor air, but concomitantly increase the mixing ratios of volatile products and, presumably, skin surface concentrations of less volatile products. Some of the volatile products, especially the dicarbonyls, may be respiratory irritants. Some of the less volatile products may be skin irritants.

来源:Hazardous Substances Data Bank (HSDB)

代谢

角鲨烯被代谢成胆固醇。

Squalene is metabolized to cholesterol.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴定和使用：鲨烯是一种液体。鲨烯通常来源于鲨鱼肝，有时也来自橄榄油。它被用作传统药物、实验性药物和膳食补充剂。鲨烯是一些佐剂的一个组成部分，这些佐剂被添加到疫苗中，以增强免疫反应。MF59是添加到FLUAD流感疫苗中的一种佐剂，就是一个这样的例子。鲨烯本身不是佐剂，但是鲨烯与表面活性剂的乳液能增强免疫反应。鲨烯也存在于各种食品和化妆品中。人类暴露和毒性：鲨烯不是显著的人类皮肤刺激物或致敏物。有限的接触致敏测试表明鲨烯不是一个显著的接触过敏原或刺激物。自1997年以来，已有2200万剂含有鲨烯的FLUAD流感疫苗被安全接种。这种疫苗每剂含有大约10毫克的鲨烯。没有与疫苗相关的严重不良事件。观察到一些轻微的局部反应。对含有鲨烯的疫苗在婴儿和新生儿身上进行的临床研究没有发现安全问题。在海湾战争老兵慢性多症状疾病的原因中，鲨烯是众多可能暴露之一，被认为存在于炭疽疫苗中。然而，进一步的研究没有发现鲨烯抗体状态与慢性多症状疾病之间的关联。大多数成年人，无论是否接种过含有鲨烯的疫苗，都对鲨烯有抗体。疫苗佐剂鲨烯的遗传毒性潜力通过人类淋巴细胞的染色体畸变（CAs）、姐妹染色单体交换（SCEs）和微核（MNs）测试以及人类淋巴细胞的彗星试验进行了评估。鲨烯在所有体外处理中都没有影响CAs和MN频率。在几乎所有浓度的24小时处理中观察到SCEs的显著增加。鲨烯在所有体外处理中都没有显著影响彗星尾部长度（CTL）（除了2500微克/毫升）和彗星尾强度（CTI）。因此，鲨烯不能被视为人类淋巴细胞的遗传毒性物质。动物研究：鲨烯的所有途径的急性动物毒性都较低。鲨烯在100%浓度下对兔皮肤和眼睛无刺激性。饮食中的鲨烯促进了小鼠HDL-胆固醇和过氧化物酶1的变化，减少了脂蛋白和血浆丙二醛水平的活性氧种类。鲨烯乳液在20%和10%乳液时增加了炎症，在5%油乳液腹腔接种牙鲆后，炎症反应温和。在大鼠淋巴细胞遗传毒性分析中，鲨烯在某些剂量中显著增加了CTL和CTI。

IDENTIFICATION AND USE: Squalene is a liquid. The source of squalene is usually from shark liver and sometimes from olive oil. It is used as traditional medicine, experimental medication, and dietary supplement. Squalene is a component of some adjuvants that are added to vaccines to enhance the immune response. MF59, an adjuvant added to the FLUAD flu vaccine, is such an example. Squalene by itself is not an adjuvant, but emulsions of squalene with surfactants do enhance the immune response. Squalene is also found in a variety of foods, cosmetics. HUMAN EXPOSURE AND TOXICITY: Squalene is not a significant human skin irritant or sensitizer. Limited contact sensitization tests indicate squalene is not a significant contact allergen or irritant. Twenty two million doses of the influenza vaccine FLUAD have been administered safely since 1997. This vaccine contains about 10 mg of squalene per dose. No severe adverse events have been associated with the vaccine. Some mild local reactions have been observed. Clinical studies on squalene-containing vaccines have been done in infants and neonates without evidence of safety concerns. One of the many possible exposures suspected of causing chronic multisymptom illnesses of Gulf War veterans is squalene, thought to be present in anthrax vaccine. However further studies found no association between squalene antibody status and chronic multisymptom illness. Most adults, whether or not they have received vaccines containing squalene, have antibodies against squalene. The genotoxic potential of the vaccine adjuvant squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in human lymphocytes. Squalene did not affect the CAs and MN frequency, in all treatments in vitro. A significant increase in SCEs was observed in almost all concentrations at 24 hr treatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500 ug/mL) and comet tail intensity (CTI) at all treatments in vitro. Therefore, squalene cannot be regarded as genotoxic in human lymphocytes. ANIMAL STUDIES: The acute animal toxicity of squalene by all routes is low. Squalene was nonirritant to rabbit skin and eye at 100% concentration. Dietary squalene promotes changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen species in lipoproteins and plasma malondialdehyde levels in mice. Squalene emulsion showed increased inflammation at 20% and 10% emulsions and the inflammatory response was mild at a concentration of 5% oil emulsion after intra-peritoneal vaccination of olive flounder. In rat lymphocytes genotoxicity assays squalene significantly increased and decreased CTL and CTI in some doses.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

该研究旨在确定人角质形成细胞对太阳紫外辐射的代谢和炎症反应的内源性脂质介质。将生理相关剂量的模拟太阳UVA+UVB应用于人类皮肤表面脂质（SSL）或原代正常人类表皮角质形成细胞（NHEK）培养中。分析了SSL中光敏感脂溶性成分、α-生育酚、角鲨烯（Sq）和胆固醇的衰减，并从照射的SSL中定量分离出角鲨烯光氧化产物（SqPx）。当直接施用于NHEK时，低剂量太阳UVA+UVB引起了时间依赖性的炎症和代谢反应。为了模拟UVA+UVB的作用，将NHEK暴露于完整的或光氧化的SSL、Sq或SqPx、4-羟基-2-壬烯醛（4-HNE）以及色氨酸光氧化产物6-甲酰吲哚[3,2-b]咔唑（FICZ）。FICZ仅激活了特有于紫外线的代谢反应，即芳基烃受体（AhR）机制及其下游的CYP1A1/CYP1B1基因表达，而4-HNE略微刺激了紫外线标志物IL-6、COX-2和iNOS基因的炎症。相比之下，SqPx诱导了大多数特有于UVA+UVB的代谢和炎症反应，作用于AhR、EGFR和G蛋白偶联的花生四烯酸受体（G2A）。这些发现表明，Sq可能是人类SSL中太阳紫外辐射的主要感应器，其光氧化产物介导/诱导角质形成细胞对UVA+UVB的代谢和炎症反应，这可能与阳光暴露的油性皮肤炎症相关。

The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components, alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time-dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4-HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2-b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR, EGFR, and G-protein-coupled arachidonic acid receptor (G2A). /These/ findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

活性氧被认为与帕金森病（PD）的发病机制有关；因此，抗氧化剂作为一种预防这种疾病的潜在方法受到了关注。鲨烯是一种天然的三萜类化合物，也是胆固醇生物合成的一个中间体，已知具有清除活性氧的作用。鲨烷是通过完全氢化鲨烯合成的，不具有清除活性氧的作用。我们研究了口服鲨烯或鲨烷对通过侧脑室注射6-羟基多巴胺（6-OHDA）建立的PD小鼠模型的影响。在6-OHDA一次性注射前后各7天给予鲨烯，可以防止纹状体多巴胺（DA）水平的降低，而同样给予鲨烷则增强了水平。无论是鲨烯还是鲨烷连续给药7天，都没有改变纹状体中过氧化氢酶、谷胱甘肽过氧化物酶或超氧化物歧化酶的活性。鲨烷增加了纹状体中的硫代巴比妥酸反应物质，这是脂质过氧化的一个标志。鲨烷和鲨烯都增加了纹状体中亚油酸与亚麻酸的比例。这些结果表明，鲨烯或鲨烷的给药在纹状体中引起了类似的脂肪酸组成变化，并对活性氧清除酶的活性没有影响。然而，鲨烷增加了纹状体的氧化损伤，加剧了6-OHDA的毒性，而鲨烯则预防了这一点。在这个模型中，鲨烯或鲨烷治疗的效果表明了它们在PD治疗中可能的用途和风险。

Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

一项小鼠研究表明，角鲨烯能够对致命的全身辐射提供辐射防护。

A mouse study showed squalene to confer radioprotection against lethal whole-body radiation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究旨在评估角鲨烯对化疗药物阿霉素（多柔比星，Dox）遗传毒性的保护作用，使用两种遗传毒性检测方法：微核试验和彗星试验。将不同组的小鼠以1和4毫摩尔/克体重的剂量喂食角鲨烯（作为角鲨烯油分别为100或400微升），在Dox（20毫克/千克）治疗前4小时或治疗后1小时进行。Dox治疗24小时后，评估骨髓红细胞微核的发生率，并通过碱性彗星试验检查心脏组织中诱导的DNA链断裂。如预期，Dox显著诱导了多色（未成熟）红细胞以及总红细胞中的微核。在Dox给药前后接受角鲨烯治疗的小鼠中，Dox诱导的微核红细胞频率显著降低。角鲨烯本身显然没有在骨髓红细胞中诱导任何微核。彗星试验也显示，与对照相比，Dox处理组小鼠的DNA损伤显著增加，尤其是DNA单链断裂。在Dox治疗前后给予角鲨烯也有效地减少了Dox诱导的DNA损伤。角鲨烯本身没有诱导任何显著的DNA损伤。与角鲨烯治疗前相比，治疗后更能有效地预防Dox诱导的DNA损伤。数据表明，将角鲨烯与Dox联合使用将有利于减少Dox在癌症化疗中的不利影响，例如减少不必要的诱变副作用的发生率。

The present study aims to evaluate the protective effect of squalene against the genotoxicity of the chemotherapeutic agent doxorubicin (Dox) using two genotoxicity assays, the micronucleus assay and the comet assay. Different groups of mice were fed squalene at the doses of 1 and 4 mmol/g body weight (100 or 400 uL as squalene oil) either at 4 hr before or 1 hr after Dox (20 mg/kg) treatment. 24 hr after the Dox treatment, bone marrow erythrocytes were evaluated for the incidence of micronuclei, and the induced DNA strand breaks were examined in heart tissue by the alkaline comet assay. As expected, Dox significantly induced micronuclei in polychromatic (immature) erythrocytes, as well as in total erythrocytes. The frequency of Dox-induced micronucleated erythrocytes was significantly reduced in the mice treated with squalene both before and after Dox administration. Squalene itself obviously did not induce any micronuclei in bone marrow erythrocytes. The comet assay also demonstrated a significant increase in DNA damage, especially DNA single strand breaks in the Dox-treated group of mice as compared to the control. The Dox-induced DNA damage was also effectively reduced by squalene when it was administered either before or after the Dox treatment. Squalene did not induce any significant DNA damage by itself. Compared to the pre-treatment of squalene, post treatment gave rise to more effective prevention against Dox-induced DNA damage. The data suggest that the complimentary use ofsqualene with Dox will be beneficial to reduce the adverse effect of Dox in cancer chemotherapy, such as the increased incidence of undesirable mutagenic side effects.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

鲨烯被用于某些乳化疫苗佐剂的油相中，但其在人体肌肉内注射后的命运作为疫苗成分尚不清楚。在本研究中，我们构建了一个基于生理的药代动力学（PBPK）模型，用于肌肉内注射的鲨烯-水（SQ/W）乳剂，以便对单次肌肉内注射后鲨烯在人体组织分布进行定量估计。该PBPK模型结合了鲨烯的相关理化性质；估计了SQ/W乳剂破裂的时间过程；注射部位及远处的解剖和生理参数；以及局部的、优先的淋巴运输。模型预测，单剂量的SQ/W乳剂将在肌肉内注射后六天内从人体三角肌中移除。大部分注射的鲨烯将分布到引流淋巴结和脂肪组织中。模型表明，从后者部位缓慢衰减，最可能是因为在中性脂质中的分配以及在该处鲨烯生物转化的低速率。对小鼠肌肉的平行药代动力学建模表明，SQ/W乳剂的动力学与在该物种中报告的含鲨烯的商业佐剂的免疫动力学时间过程相对应。总之，本研究对含鲨烯乳剂在人体中的命运做出了重要的药代动力学预测。本研究的结果可能对于理解这类新型疫苗佐剂的免疫动力学有相关性，并可能在未来的定量风险分析中，包含作用机制数据时有所帮助。

Squalene is used in the oil phase of certain emulsion vaccine adjuvants, but its fate as a vaccine component following intramuscular (IM) injection in humans is unknown. In this study, we constructed a physiologically-based pharmacokinetic (PBPK) model for intramuscularly injected squalene-in-water (SQ/W) emulsion, in order to make a quantitative estimation of the tissue distribution of squalene following a single IM injection in humans. The PBPK model incorporates relevant physicochemical properties of squalene; estimates of the time course of cracking of a SQ/W emulsion; anatomical and physiological parameters at the injection site and beyond; and local, preferential lymphatic transport. The model predicts that a single dose of SQ/W emulsion will be removed from human deltoid muscle within six days following IM injection. The major proportion of the injected squalene will be distributed to draining lymph nodes and adipose tissues. The model indicates slow decay from the latter compartment most likely due to partitioning into neutral lipids and a low rate of squalene biotransformation there. Parallel pharmacokinetic modeling for mouse muscle suggests that the kinetics of SQ/W emulsion correspond to the immunodynamic time course of a commercial squalene-containing adjuvant reported in that species. In conclusion, this study makes important pharmacokinetic predictions of the fate of asqualene-containing emulsion in humans. The results of this study may be relevant for understanding the immunodynamics of this new class of vaccine adjuvants and may be useful in future quantitative risk analyses that incorporate mode-of-action data.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

超过60%的摄入的角鲨烯从小肠吸收；从这里它以乳糜微粒的形式通过淋巴进入系统循环。在血液中，角鲨烯主要携带在极低密度脂蛋白中，并分布到身体的各种组织中。很大比例的角鲨烯被分布到皮肤。

Over 60% of ingested squalene is absorbed from the small intestine; from there it is carried in the lymph in the form of chylomicrons into the systemic circulation. In the blood, squalene is carried mainly in very-low-density lipoproteins and distributed to the various tissues of the body. A large percentage of squalene gets distributed to the skin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

动物研究表明，角鲨烯会通过皮肤缓慢吸收，而角鲨烷和角鲨烯这两种化合物都很难通过胃肠道吸收。

Animal studies indicate Squalene is slowly absorbed through the skin, while both compounds /Squalane and Squalene/ are poorly absorbed from the gastrointestinal tract.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 安全说明：
  S24/25
• WGK Germany：
  2
• 海关编码：
  29012980
• RTECS号：
  XB6010000
• 包装等级：
  II; III
• 危险类别：
  4.1
• 危险标志：
  GHS08
• 危险性描述：
  H304
• 危险性防范说明：
  P301 + P310,P331

制备方法与用途

简介

反式角鲨烯是一种具有异戊二烯结构的全反式三萜烯化合物，含有6个双键，因此性质极不稳定，容易氧化。它在抑制氧化应激和清除体内的炎症因子方面表现出较好的功能特性，被广泛应用于食品、医药和化妆品等领域。

功能特性

反式角鲨烯是一种强大的抗氧化物质，在体内能阻断氧化应激过程引起的生理学病变，并通过影响酶和细胞的活性，调节细胞因子、多种物质的水平及信号传递。它能够降低胆固醇合成、提高免疫系统能力、抑制肿瘤细胞生成，以及减轻外界毒性物质对机体的不良影响。

生物活性

反式角鲨烯（Spinacene, Supraene）自然存在于植物、动物和人体中，是一种添加在疫苗佐剂中的成分，用于增强免疫反应。

靶点

Human Endogenous Metabolite

化学性质

本品是从深海鲨鱼肝或肝油中制得。它是由6个异戊二烯构成的不饱和脂肪烯烃，属于非环式的三萜结构。为无色或微黄色油状澄明液体；有特异鱼肝油萜臭。熔点-75℃，沸点240-242℃/266.644Pa，密度0.854-0.862g/cm³，折射率为1.494-1.499。能与乙醚、四氯化碳和丙酮任意混合，不溶于水。易氧化。

用途 营养药

内服治疗高、低血压、贫血、糖尿病、肝硬化、癌症、便秘、虫牙；外敷治疗扁桃腺炎、喘息、支气管炎、感冒、结核、鼻炎、胃溃疡、十二指肠溃疡、胆、膀胱结石、风湿病、神经痛等。

溶剂

气相色谱固定液（最高使用温度140℃，溶剂为甲苯），分离分析烃类化合物。

生产方法 方法一：以鲨鱼肝油为原料

将鲨鱼肝油减压蒸馏，得3.5%的含姥鲨烷初制品。再通过硅油浴加热进行减压蒸馏，收集第I和第II馏分，最终得到精制的反式角鲨烯。

方法二：以鲸鲨肝脏为原料

取新鲜冰冻的鲸鲨肝，去血水后剪碎并匀浆，经过皂化、分离等步骤获得粗制品。再通过减压蒸馏进行多次蒸馏，收集无色透明的油状物，即精制的反式角鲨烯。

方法三：以鲨肝为原料

取新鲜冰冻鲸鲨肝脏，去血水后剪碎并匀浆，经过皂化、分离等步骤获得粗制品。再通过减压蒸馏进行多次蒸馏，收集无色透明的油状物，即精制的反式角鲨烯。

反应信息

• 作为反应物：
  描述：

  角鲨烯 在 氢气 作用下， 100.0 ℃ 、4.0 MPa 条件下， 反应 24.0h， 以98%的产率得到角鲨烷
  参考文献：
  名称：

  固定在原始埃洛石上的镍纳米颗粒：一种出色的氢化过程催化剂

  摘要：

  一种可持续的纳米材料：纳米粘土（埃洛石）和第一排过渡金属（镍）之间的合作产生了一种多功能催化剂，允许通过加氢过程合成目标产品，同时具有显着的选择性和高效的催化剂回收。

  DOI：

  10.1002/cctc.202200775
• 作为产物：
  描述：

  2,3环氧角鲨烯 在 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 作用下， 以70%的产率得到角鲨烯
  参考文献：
  名称：

  有机合成中的三氟甲磺酸三甲硅烷基酯1

  摘要：

  三氟甲磺酸三甲基甲硅烷基酯是有机化合物的强大甲硅烷基化剂，并充当催化剂，可加速非质子介质中的各种亲核反应。反应通过甲硅烷基与杂官能团的单中心亲电配位进行，并表现出独特的选择性。

  DOI：

  10.1016/s0040-4020(01)93263-6
• 作为试剂：
  描述：

  二硫化二苯并噻唑 在 角鲨烯 作用下， 生成 2-巯基苯并噻唑
  参考文献：
  名称：

  Nakasaki, Nippon Kagaku Zasshi, 1953, vol. 74, p. 518

  摘要：

  DOI：

文献信息

• Ti/Pd Bimetallic Systems for the Efficient Allylation of Carbonyl Compounds and Homocoupling Reactions
  作者：Alba Millán、Araceli G. Campaña、Btissam Bazdi、Delia Miguel、Luis Álvarez de Cienfuegos、Antonio M. Echavarren、Juan M. Cuerva

  DOI：10.1002/chem.201003315

  日期：2011.3.28

  The allylation, crotylation and prenylation of aldehydes and ketones with stable and easily handled allylic carbonates is promoted by a Ti/Pd catalytic system. This Ti/Pd bimetallic system is especially convenient for the allylation of ketones, which are infrequent substrates in other related protocols, and can be carried out intramolecularly to yield five‐ and six‐membered cyclic products with good

  Ti / Pd催化体系可促进醛和酮与稳定且易于处理的烯丙基碳酸酯的烯丙基化，丁酰化和烯丙基化。这种Ti / Pd双金属体系特别适合于酮的烯丙基化，酮是其他相关规程中不常见的底物，并且可以在分子内进行生产，从而产生具有良好立体选择性的五元和六元环状产物。此外，Ti / Pd介导的还原反应和Würtz型二聚反应可以很容易地从碳酸烯丙酯和羧酸酯中进行。
• Synthese von Squalen aus natürlichem und synthetischem Nerolidol
  作者：O. Isler、R. Rüegg、L. Chopard-dit-Jean、H. Wagner、Karl Bernhard

  DOI：10.1002/hlca.19560390334

  日期：——

  Squalene was synthesized in a modified procedure according to P. Karrer & A. Helfensteiqa starting from naturel and from synthetic nerolidol. After purification through the thio-urea adduct the synthetic products were found to be identical with pure natural squalene in their chemical and physical properties as well as in their biological behaviour.

  根据P.Karrer和A.Helfensteiqa，以天然和合成的橙花醇为原料，按照改进的方法合成鲨烯。通过硫脲加合物纯化后，发现合成产物在化学和物理性质以及生物学行为方面与纯天然角鲨烯相同。
• Ring Opening of Oxiranes by Trimethylsilyl Trifluoromethanesulfonate
  作者：Sizuaki Murata、Masaaki Suzuki、Ryoji Noyori

  DOI：10.1246/bcsj.55.247

  日期：1982.1

  Trimethylsilyl trifluoromethanesulfonate promotes ring opening reactions of oxirane derivatives. The reaction course is highly affected by the structures and substitution pattern of the substrates. Tetra-, tri-, and 2,2-disubstituted oxiranes and simple cycloalkene oxides are converted to the corresponding allylic alcohol trimethylsilyl ethers. The overall transformation is interpreted in terms of

  Trimethylsilyl trifluoromethanesulfonate 促进环氧乙烷衍生物的开环反应。反应过程受底物结构和取代模式的影响很大。四-、三-和2,2-二取代的环氧乙烷和简单的环烯氧化物被转化为相应的烯丙醇三甲基甲硅烷基醚。总体转化解释为三氟甲磺酸甲硅烷基酯反式加成到环氧乙烷环上，然后是碱促进的三氟甲磺酸元素的反消除。2,3-二烷基-或单烷基环氧乙烷分别异构化为相应的酮和醛。(Z)-氧化环辛烯经历跨环反应生成内-顺-2-三甲基甲硅烷氧基双环[3.3.0]辛烷。6-methyl-5-hepten-2-one 氧化物反应生成 2,2, 6-trimethyl-3-trimethylsiloxy-3,4-dihydro-2H-pyran。1,2-甲基迁移发生在 (E)-3α-t-丁基二甲基甲硅烷氧基-5α-孕烯 17α,20-氧化物反应中，得到 3α-t-丁基二甲基...
• Selective Deoxygenation of Allylic Alcohol: Stereocontrolled Synthesis of Lavandulol
  作者：Hee Jin Kim、Liang Su、Heejung Jung、Sangho Koo

  DOI：10.1021/ol200779y

  日期：2011.5.20

  Selective deoxygenation of allylic alcohol can be successfully carried out by the formation of alkoxyalkyl ether (EE or MOM), followed by Pd(dppe)Cl2-catalyzed reduction with LiBHEt3. (+)-S-Lavandulol has been efficiently synthesized by the application of this protocol to the diol derived from the Pb(OAc)4-promoted oxidative ring-opening of (−)-R-carvone. This deoxygenation method is general and selective

  通过形成烷氧基烷基醚（EE或MOM），然后用LiBHEt 3催化Pd（dppe）Cl 2催化还原，可以成功地进行烯丙醇的选择性脱氧。通过将该方案应用于衍生自Pb（OAc）4促进的（-）- R-香芹酮的氧化开环的二醇，已有效地合成了（+）- S - Lavandulol。该脱氧方法对烯丙基醇是通用的和选择性的。
• Inhibitory Activity of 8-Azadecalin Derivatives towards 2,3-Oxidosqualene: Lanosterol Cyclases from Baker’s Yeast and Pig’s Liver
  作者：Tsutomu Hoshino、Naoto Kobayashi、Eiichi Ishibashi、Shuji Hashimoto

  DOI：10.1271/bbb.59.602

  日期：1995.1

  8-azadecalin derivatives. Strong inhibitory activity was observed for those compounds having carbon chains around C12. Interestingly, the amide compounds (not the carbocationic intermediate) exhibited remarkably strong inhibition toward the liver cyclase, whereas they had an insignificant effect on the yeast cyclase (about 10(2)-fold less active). The yeast cyclase needed the amine functionality (carbocationic

  通过猪肝和贝克酵母的对比研究，研究了2,3-氧化角鲨烯：羊毛甾醇环化酶的抑制剂。抑制剂的基本骨架是8-azadecalin。通过与NaCNBH 3的还原胺化反应，将异戊二烯样链[神经节丙酮（Z-形式），香叶基丙酮（E-形式）或其氢化形式]连接到氮原子上。在这三种形式中，Z-异构体是对猪肝脏和酵母环化酶最有效的抑制剂。为了检查碳链长度（亲脂性）的影响，将各种脂肪酸（C6-C18）附加到8-azadecalin衍生物上。对于在C12附近具有碳链的那些化合物，观察到强的抑制活性。有趣的是 酰胺化合物（不是碳正离子中间体）对肝脏环化酶表现出显着的抑制作用，而对酵母环化酶的作用却微不足道（活性降低约10（2）倍）。酵母环化酶需要胺官能团（碳酸盐中间体），该胺官能团是通过使用LiAlH4从相应的酰胺中制备的，以表现出有效的抑制作用。我们发现，在任何已知物质中，N-十二烷基-8-氮杂-4,4,10β-三

表征谱图