豆甾醇 | 83-48-7

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 豆甾醇
• 中文别名: 植物甾醇；3-去氮腺嘌呤A；豆固醇；甾醇
• 英文名称: Stigmasterol
• 英文别名: stigmasterin；β-stigmasterol；stigmasta-5,22-dien-3β-ol；(3β,22E)-stigmasta-5,22-dien-3-ol；(3S,8S,9S,10R,13R,14S,17R)-17-[(E,2R,5S)-5-ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 83-48-7
• 化学式: C₂₉H₄₈O
• 分子量: 412.7
• InChiKey: HCXVJBMSMIARIN-PHZDYDNGSA-N

物化性质

• 熔点：
  165-167 °C (lit.)
• 比旋光度：
  -50 º (c=2, CHCl3)
• 沸点：
  472.07°C (rough estimate)
• 密度：
  0.9639 (rough estimate)
• 溶解度：
  在氯仿的溶解度为50mg/ml
• 最大波长(λmax)：
  226nm(MeOH)(lit.)
• LogP：
  10.072 (est)
• 物理描述：
  Solid
• 蒸汽压力：
  1.62X10-10 mm Hg at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

植物甾醇的代谢是通过使用大鼠粪便和肝脏微粒体来研究的。在给大鼠口服植物甾醇（一种特征明确的混合物，包含40%的β-谷固醇、30%的菜油固醇和20%的δ-谷固醇）后，收集了粪便（剂量为0.5克/千克）。使用气相色谱/质谱（GC/MS）鉴定植物甾醇的代谢物。三个峰在12.47、12.65、12.87分钟的保留时间被洗脱，并分别具有特征性的分子离子m/z 428、430、432。三种粪便代谢物被鉴定为雄烯二酮、雄烯二酮和雄烷二酮。在大鼠肝脏微粒体反应混合物中没有检测到代谢物。结果表明，在大鼠大肠中，植物甾醇的代谢物是通过3-位的氧化、5-和6-位的饱和以及17-侧链的断裂形成的。

Metabolism of phytosterols was investigated using rat feces and liver microsomes. Feces were collected after phytosterols (a well characterized mixture of beta-sitosterol 40%, campesterol 30% and dihydrobrasicasterol) were administered orally (0.5 g/kg) to rats. Metabolites of phytosterols were identified using GC/MS. Three peaks were eluted at 12.47, 12.65, 12.87 min and had characteristic molecular ions m/z 428, 430, 432, respectively. Three fecal metabolites were identified as androstadienedione, androstenedione, and androstanedione. No metabolites could be detected in the rat liver microsomal reaction mixture. The results suggest that the metabolites of phytosterols in rat feces are formed by oxidation at 3- position, saturation at 5- and 6- position, and 17- side chain cleavage in the rat large intestine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

植物甾醇是所有真核生物膜的重要组成成分。它们可以通过从头合成或从环境中吸收获得。它们的功能似乎是控制膜的流动性和通透性，尽管一些植物甾醇在信号转导中具有特定的功能。植物甾醇是异戊二烯途径的产物。光合植物中甾醇合成的专门途径发生在角鲨烯阶段，通过角鲨烯合酶的活性实现。尽管3-羟基-3-甲基戊二酸辅酶A（HGMR）的活性在胆固醇合成中是限速的，但这似乎并不适用于植物甾醇。HGMR的上调似乎增加了环阿屯醇的生物合成，但不是delta5-甾醇。甾醇合成的下降与角鲨烯合酶活性的抑制有关，这可能是控制碳流和终产品形成的临界点。主要的角鲨烯后生物合成途径受到关键的限速步骤的调控，如环阿屯醇甲基化成环异绿醇。关于控制终点甾醇酯或甾烷醇生物合成的因素知之甚少。

Plant sterols are an essential component of the membranes of all eukaryotic organisms. They are either synthesized de novo or taken up from the environment. Their function appears to be to control membrane fluidity and permeability, although some plant sterols have a specific function in signal transduction. The phytosterols are products of the isoprenoid pathway. The dedicated pathway to sterol synthesis in photosynthetic plants occurs at the squalene stage through the activity of squalene synthetase. Although the activity of 3-hydroxymethyl-3-glutaryl coenzyme A (HGMR) is rate-limiting in the synthesis of cholesterol, this does not appear to be the case with the plant sterols. Up-regulation of HGMR appears to increase the biosynthesis of cycloartenol but not the delta5-sterols. A decline in sterol synthesis is associated with a suppression of squalene synthetase activity, which is probably a critical point in controlling carbon flow and end-product formation. The major post-squalene biosynthetic pathway is regulated by critical rate-limiting steps such as the methylation of cycloartenol into cycloeucalenol. Little is known about the factors controlling the biosynthesis of the end-point sterol esters or stanols.

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：对于昏迷、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"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（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……。 /毒物A和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/在一项研究中，对12名健康男性和12名女性（平均年龄36岁）进行了评估，以研究富含植物甾醇酯的黄油对粪便中胆酸和甾醇浓度的影响。在磨合期，志愿者连续21天（如果是男性）或28天（如果是女性）每天消耗40克控制黄油。然后将一半的志愿者随机分配，继续消耗控制黄油21天或28天。剩余的受试者消耗了含有8.6克植物油植物甾醇（46%（w/w）β-谷甾醇，26%菜油甾醇，20%豆甾醇）的黄油。在整个研究过程中，受试者消耗相同的饮食，并根据个人的能量需求进行调整。富含植物甾醇酯的涂抹物显著增加了粪便中中性甾醇的浓度，从大约40毫克/克增加到190毫克/克干重粪便。粪便中性甾醇代谢物从大约30毫克/克增加到大约50毫克/克。主要排泄的亲甾醇是胆固醇、谷甾醇、菜油甾醇和豆甾醇。谷甾醇、菜油甾醇和豆甾醇分别占粪便中性甾醇总量的28%、15%和12%，反映了富含甾醇的黄油的组成。主要排泄的甾醇代谢物是由3位氧化形成的代谢物和在β-构型中5,6位饱和的代谢物。植物油甾醇将粪便中次级胆酸浓度从7.6毫克/克干粪便降低到6.0毫克/克。消耗植物油植物甾醇略微但显著增加了粪便中4-胆甾-3-酮的浓度。然而，4-胆甾-3-酮的浓度仍然非常低（小于2毫克/克），并且与文献中报告的食用高脂肪或低脂肪饮食的受试者的值相符。粪便中没有检测到甾醇氧化物...

/HUMAN EXPOSURE STUDIES/ A study was conducted in 12 healthy males and 12 females (mean age 36 years) to assess the impact of a margarine enriched with phytosterol esters on fecal concentrations of bile acids and sterols. During the run-in period, volunteers consumed 40 g of a control margarine for 21 consecutive days if male, and for 28 days if female. Half of the volunteers were then randomly allocated to consume the control margarine for another 21 or 28 days, respectively. The remaining subjects consumed 40 g of a margarine containing 8.6 g vegetable oil phytosterol (46% (w/w) beta-sitosterol, 26% campesterol, 20% stigmasterol). Throughout the total study subjects consumed the same diet adjusted for individual energy requirements. The phytosterol ester-enriched spread significantly enhanced fecal neutral sterol concentrations from about 40 mg/g to 190 mg/g dry weight faeces. Fecal neutral sterol metabolites increased from about 30 mg/g to about 50 mg/g. The major parent sterols excreted were cholesterol, sitosterol, campesterol and stigmasterol. Sitosterol, campesterol and stigmasterol comprised 28%, 15% and 12% of the total fecal neutral sterols, reflecting the composition of the sterol enriched margarine. The major sterol metabolites excreted were metabolites formed by, predominantly, oxidation at the 3-position and metabolites saturated at the 5,6 position in a beta-configuration. Fecal secondary bile acid concentration was reduced by vegetable oil sterols from 7.6 mg/g dry faeces to 6.0 mg/g. Consumption of vegetable oil phytosterols slightly but significantly increased the fecal concentration of 4-cholesten-3-one. However, 4-cholesten-3-one concentration remained very low (less than 2 mg/g) and in line with values reported in the literature for subjects fed high or low fat diets. No sterol oxides could be detected in the feces...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人体暴露研究...比较添加不同植物油甾醇或谷甾醇酯的人造黄油对血浆总胆固醇、LDL胆固醇和HDL胆固醇浓度的影响。...进行了一项随机双盲安慰剂对照的平衡不完全拉丁方设计研究，包括五种处理和四个周期，每个周期为3.5周。比较了添加大豆油、非洲乳木果油或米糠油甾醇或谷甾醇酯的黄油与未添加的对照组黄油。甾醇摄入量为每天1.5-3.3克。大豆油甾醇中有三分之二被酯化为脂肪酸。...招募了100名健康、非肥胖、正常胆固醇和轻度高胆固醇的志愿者，年龄为45±12.8岁，进入研究时血浆总胆固醇水平低于8 mmol/L。测量了血浆脂质、类胡萝卜素和甾醇浓度、血液临床化学和血液学、血浆胆固醇酯的脂肪酸组成和食物摄入量。95名志愿者完成了研究。所有黄油都没有引起血液临床化学、血清总胆汁酸或血液学的有害变化。与对照黄油相比，添加大豆油甾醇酯或谷甾醇酯的黄油显著降低了血浆总胆固醇和LDL胆固醇浓度8-13%（0.37-0.44 mmol/L）。对HDL胆固醇浓度没有影响。这两种黄油的LDL至HDL胆固醇比率分别降低了0.37和0.33单位。对血脂的影响在正常胆固醇和轻度高胆固醇受试者之间没有差异。与对照相比，大豆油甾醇黄油的血浆豆甾醇和菜油甾醇水平显著升高，而谷甾醇酯黄油的这些水平显著降低。饮食摄入在各处理间非常相似。血浆胆固醇酯的脂肪酸组成证实了对治疗的良好依从性。所有甾醇强化黄油都降低了以脂质为标准的血浆α和β-胡萝卜素水平。血浆番茄红素水平也有所降低，但这种效果对所有产品来说并不显著。...

/HUMAN EXPOSURE STUDIES/ ... To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester.... A randomized double-blind placebo-controlled balanced incomplete Latin square design /study/ with five treatments and four periods of 3.5 weeks /was conducted/. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol intake was between 1.5-3.3 g/d. Two thirds of the soybean oil sterols were esterified to fatty acids. ... One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolemic volunteers aged 45+/-12.8 y, with plasma total cholesterol levels below 8 mmol/L at entry /were recruited/. Plasma lipid, carotenoid and sterol concentrations, blood clinical chemistry and hematology, fatty acid composition of plasma cholesterylesters and food intake /were measured/. Ninety-five volunteers completed the study. None of the margarines induced adverse changes in blood clinical chemistry, serum total bile acids or haematology. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8-13% (0.37-0.44 mmol/L) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines, respectively. Effects on blood lipids did not differ between normocholesterolemic and mildly hypercholesterolemic subjects. Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control. Dietary intake was very similar across treatments. The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment. All sterol enriched margarines reduced lipid-standardized plasma alpha- plus beta-carotene levels. Plasma lycopene levels were also reduced but this effect was not significant for all products. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

以模仿乳糜微粒（CM）形式的脂质乳剂通过静脉注射植物固醇和角鲨烯的代谢进行了研究。这种类似CM的脂质乳剂是通过将角鲨烯溶解在市售的Intralipid中制备的。将含有6.3毫克胆固醇、1.9毫克菜油甾醇、5.7毫克谷固醇、1.6毫克豆甾醇、18.1毫克角鲨烯和6克甘油三酯的30毫升脂质乳剂作为一次性静脉注射给予六名健康志愿者。在注射前从对侧手臂抽取血液样本，并在注射后连续2.5至180分钟抽取血液样本。CM角鲨烯、植物固醇和甘油三酯的衰减是单指数的。CM角鲨烯的半衰期是74 +/- 8分钟，菜油甾醇的半衰期是37 +/- 5分钟（与角鲨烯相比P < 0.01），谷固醇、豆甾醇和甘油三酯的半衰期分别是17 +/- 2、15 +/- 1和17 +/- 2分钟（与角鲨烯和菜油甾醇相比P < 0.01）。注射180分钟后，CM角鲨烯的浓度仍然超过基线水平（P = 0.02），而植物固醇和甘油三酯在注射后45至120分钟之间返回到基线水平。角鲨烯和菜油甾醇的半衰期与它们空腹时的CM浓度正相关。此外，极低密度脂蛋白（VLDL）角鲨烯、菜油甾醇和甘油三酯浓度，VLDL、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）谷固醇浓度，以及VLDL和LDL豆甾醇浓度均有显著增加...

... Metabolism of plant sterols and squalene administered intravenously in the form of lipid emulsion mimicking chylomicrons (CM) /was studied/. The CM-like lipid emulsion was prepared by dissolving squalene in commercially available Intralipid. The emulsion was given as an intravenous bolus injection of 30 mL containing 6.3 mg of cholesterol, 1.9 mg of campesterol, 5.7 mg of sitosterol, 1.6 mg of stigmasterol, 18.1 mg of squalene, and 6 g of triglycerides in six healthy volunteers. Blood samples were drawn from the opposite arm before and serially 2.5 -180 min after the injections. The decay of CM squalene, plant sterols, and triglycerides was monoexponential. The half-life of CM squalene was 74 +/- 8 min, that of campesterol was 37 +/- 5 min (P < 0.01 from squalene), and those of sitosterol, stigmasterol, and triglycerides were 17 +/- 2, 15 +/- 1, and 17 +/- 2 min, respectively (P < 0.01 from squalene and campesterol). The CM squalene concentration still exceeded the baseline level 180 min after injection (P = 0.02), whereas plant sterols and triglycerides returned to the baseline level between 45 and 120 min after injection. The half-lives of squalene and campesterol were positively correlated with their fasting CM concentrations. In addition, VLDL squalene, campesterol, and triglyceride concentrations, VLDL, LDL, and HDL sitosterol concentrations, as well as VLDL and LDL stigmasterol concentrations were increased significantly...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大鼠通过口服灌胃给予14C标记的胆固醇、β-谷固醇或β-谷甾醇，或给予（3）H标记的β-谷甾醇、菜油甾醇、菜油甾烷醇或豆甾醇，这些样品均溶解在葵花籽油中。在给药后收集尿液和粪便，持续最多96小时。... 动物被处死，要么准备进行全身放射性自显影，要么对组织和尸体残骸进行14C或（3）H的检测。根据组织和尸体中的放射性水平判断，植物甾醇的整体吸收率较低。从体内排出主要是在粪便中，最初非常迅速，但在给药后4天内仍有物质被排出。尽管没有胆汁排泄数据无法完全量化植物甾醇的总吸收量，但很明显胆固醇的吸收程度最高（女性在24小时后为剂量的27%）。菜油甾醇（13%）的吸收高于β-谷固醇和豆甾醇（均为4%），这两者的吸收又高于β-谷甾醇和菜油甾烷醇（1-2%）。植物甾醇的吸收在雌性中略高于雄性。对于每种测试物质，放射性在组织中的分布模式相似，肾上腺、卵巢和肠上皮细胞显示出最高的放射性水平和最长的放射性保留时间。

Rats were dosed by oral gavage with 14C-labelled samples of cholesterol, beta-sitosterol or beta-sitostanol or (3)H-labelled samples of beta-sitostanol, campesterol, campestanol or stigmasterol dissolved in sunflower seed oil. Urine and feces were collected for up to 96 hours after dosing. ... Animals were sacrificed and either prepared for whole body autoradiography or tissues and carcass remains were assayed for 14C or (3)H. The overall absorption of phytosterols was low as judged by tissue and carcass levels of radioactivity. Elimination from the body was mainly in the feces and was initially very rapid, but traces of material were still being excreted at 4 days after dosing. While total absorption of the phytosterols could not be fully quantified without biliary excretion data, it was clear that cholesterol was absorbed to the greatest extent (27% of the dose in females at 24 hours). Campesterol (13%) was absorbed more than beta-sitosterol and stigmasterol (both 4%) which were absorbed more than beta-sitostanol and campestanol (1-2%). The absorption of phytosterols was slightly greater in females than males. For each test material, the overall pattern of tissue distribution of radioactivity was similar, with the adrenal glands, ovaries and intestinal epithelia showing the highest levels and the longest retention of radioactivity.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

胆固醇、菜油甾醇、菜油甾烷醇、豆甾醇和谷甾醇在小肠的吸收通过在小肠上段50厘米的肠内灌注技术进行了测量，使用谷甾烷作为不可吸收的标记物。在10名健康受试者中，胆固醇的吸收率最高，平均为33%，而谷甾醇的吸收率平均为4.2%，豆甾醇的吸收率为4.8%...

Intestinal absorption of cholesterol, campesterol, campestanol, stigmasterol and sitosterol were measured in 10 healthy subjects by an intestinal perfusion technique over a 50 cm segment of the upper jejunum using sitostanol as non-absorbable marker. Cholesterol absorption was highest and averaged 33%., whereas the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%....

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了研究饮食中豆甾醇对固醇和胆汁酸代谢的影响，将Wistar大鼠喂食含有不同量豆甾醇的饮食。高剂量豆甾醇的喂养（每日11、26或52毫克）导致了胆固醇、粪甾醇和胆汁酸排出量的增加。这些效果与剂量相关，并且可能与植物固醇对胆固醇吸收的抑制效果有关。此外，这也解释了豆甾醇降低胆固醇的有益效果。

To study the effects of dietary stigmasterol on sterol and bile acids metabolism, Wistar rats were fed diets containing various amounts of stigmasterol. Feeding high stigmasterol doses (11, 26 or 52 mg/day) led to increased cholesterol, coprostanol and bile acid output. These effects were dose-dependent, and likely to be related to the inhibitory effect of plant sterols on cholesterol absorption. Moreover, it accounts for the beneficial effect of the stigmasterol on cholesterol lowering.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

烟草甾醇（胆固醇、β-谷甾醇、菜油甾醇和豆甾醇）存在于烟草烟雾中，并且会出现在暴露于香烟烟雾的哺乳动物血浆中。因为烟草甾醇可能在吸烟引起的肺和血管疾病的发病机制中起重要作用，...研究了香烟甾醇在大鼠肺部的沉积模式以及香烟甾醇在大鼠血浆和身体器官中的出现情况。在暴露于标记有[4-14C]胆固醇或β-[4-14C]谷甾醇的烟草烟雾（每次5毫升，共二十次）后，大鼠在暴露后立即（第0天）以及在第2、5、8、11、15和30天被处死，并分析了肺和选定的身体器官的活性。...香烟甾醇与香烟烟雾中的颗粒物相关，主要沉积在肺远端空气空间和肺实质中，并且在大鼠单次暴露于香烟烟雾后30多天内仍会在血浆和几个身体器官中出现。支气管肺泡灌洗液在最初的几天内含有相对少量的放射性标记，这表明大部分甾醇被迅速吸收进入肺实质中...

Tobacco sterols (cholesterol, beta-sitosterol, campesterol, and stigmasterol) are present in tobacco smoke and appear in plasma of mammals exposed to cigarette smoke. Because tobacco sterols may be important in the pathogenesis of smoking-induced lung and vascular diseases, ... the pattern of deposition of cigarette sterols in the lungs and appearance of cigarette sterols in plasma and body organs of rats /were studied/. After exposure to twenty 5 mL "puffs" of smoke from tobacco labeled with [4-14C]cholesterol or beta-[4-14C]sitosterol, rats were killed just after exposure (day 0) and on days 2, 5, 8, 11, 15, and 30, and the lungs and selected body organs analyzed for activity. ... Cigarette sterols /were/ associated with particulates in cigarette smoke, deposited mostly in distal airspaces and parenchyma of the lungs, and appear in plasma and several body organs for more than 30 days after this single exposure to cigarette smoke. Bronchoalveolar lavage fluid contained relatively small amounts of radiolabel for only the first few days, suggesting that most of the sterols were rapidly incorporated in lung parenchyma...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn,Xi
• 安全说明：
  S22,S24/25,S36/37
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2906199090
• 危险品运输编号：
  UN 1888 6.1/PG 3
• RTECS号：
  WJ2447500

制备方法与用途

豆甾醇简介

豆甾醇属于天然植物甾醇的一种，存在于各种植物油中，广泛应用于医药、食品和化妆品等行业。在一些植物如汉防己、黄柏、毒扁豆及马铃薯等中也含有豆甾醇，并且它还存在于海洋浮游植物、海水和海洋沉积物中。

理化性质

• 熔点：通常为165～167℃，纯度90%时熔点在164~167℃之间。
• 旋光度：小于等于-30゜；-51℃(c=2，氯仿)。
• 沸点：490.4°C at 760 mmHg。
• 溶解性：易溶于丙酮、氯仿、苯和醋酸乙酯，能溶于乙醇，不溶于水。

提取方法 溶剂法

通过多步萃取与重结晶分离，直接利用混合植物甾醇各组分的差异。超声波辅助提取大豆油中的豆甾醇最佳工艺条件为：超声温度50℃、超声时间40min 和液料比19mL/g。

化学反应法

Windaus和Hauth提出的溴化乙酰化物化学反应方法，通过在醋酸酐中回流生成豆甾醇醋酸酯，然后用过量的二氯丙烯进行溴化。经过脱溴、脱乙酰化处理后，在丙酮中结晶得到纯度较高的单体豆甾醇。

生产制备

• 超声波辅助提取：使用乙酸乙酯为提取剂，以大豆油为原料。
• 化学反应分离：从植物甾醇中分离除去β-谷甾醇、菜籽甾醇和菜油甾醇，得到纯度较高的单体豆甾醇。

用途

主要用作合成甾体激素的原料，也可用于维生素D3的生产。它还被广泛应用于生化研究中制备黄体酮及孕酮等药物，并具有抗癌、抗热、抗炎和免疫调节作用。

化学性质

来源于豆科植物大豆 Glycine max(L.)Merr.种子

用途

用于甾体激素合成和维生素D3生产，同时也是一种具有多种生物活性的植物甾醇。

反应信息

• 作为反应物：
  描述：

  豆甾醇 在 咪唑 、 1% Pd on activated carbon 、 ammonium acetate 、 氢气 、 臭氧 、 三苯基氧化膦 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， -70.0~50.0 ℃ 、303.99 kPa 条件下， 反应 26.0h， 生成 胆固醇
  参考文献：
  名称：

  一种合成胆固醇的新方法

  摘要：

  本发明公开了一种合成胆固醇的新方法，包括步骤：（1）豆甾醇02溶于有机溶剂I中，在催化剂的作用下与三甲基氯硅烷进行硅醚化反应，经水洗、浓缩得化合物03；（2）化合物03溶解在有机溶剂II中进行臭氧氧化反应，再加锌粉和冰醋酸进行还原，反应完成后，过滤，洗涤，浓缩，得化合物04；（3）三苯基膦与1‑卤代‑3‑甲基丁烷反应得3‑甲基丁基三苯基卤化膦；将所述3‑甲基丁基三苯基卤化膦加入非质子溶剂中，加入强碱，然后与化合物04进行wittig反应，经中和、浓缩、过滤，得化合物05；（4）化合物05在催化剂和钝化剂的作用下在溶剂III中进行选择性氢化反应，经过滤、浓缩、结晶，得胆固醇01。该方法工艺简单，原料成本低廉，经济环保，便于工业化生产。

  公开号：

  CN106632565A
• 作为产物：
  描述：

  醋酸豆甾醇 在 二正丁基氧化锡 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 6.0h， 以10%的产率得到豆甾醇
  参考文献：
  名称：

  Mild and selective deprotection method of acetylated steroids and diterpenes by dibutyltin oxide

  摘要：

  Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and diterpene esters. The results showed the deprotection of acetylated steroids and diterpenes separately with moderate catalysis dibutyltin oxide in methanol selectively removed part acetyl groups of these substrates, whereas several functional groups of the steroids and diterpenes were retained and neither isomerization nor degradation of these substrates was observed. It seems that the acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl groups can be cleaved by the reaction, whereas the acetyl groups with higher steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were retained under the same conditions. One of the interesting results obtained was the selective hydrolysis of the 3 beta-O-acetyl group in the presence of the 6 beta group in 3 beta,6 beta-Di-O-acetyl-5 alpha-hydroxypregn-16-en-20-one. This allows for subsequent introduction of one unit at C-3 and the other unit at C-6. This procedure is useful for the synthesis of a series of closely related isomers of 3 beta, 5 alpha, 6 beta-trihydroxypregn-16-en-20-one and other widespread polyhydroxysteroids in marine organisms and some terrestrial species. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2006.10.004

文献信息

• [EN] PLANT STEROIDS AND USES THEREOF<br/>[FR] STÉROÏDES VÉGÉTAUX ET LEURS UTILISATIONS
  申请人：DAVIDSON LOPEZ LLC

  公开号：WO2013040441A1

  公开（公告）日：2013-03-21

  The invention relates to a drug conjugate including a drug and a plant steroid. The drug conjugate may target the drug for intestinal cell delivery, and thus may be used to treat diseases, including intestinal diseases, or to affect intestinal metabolism. The invention therefore also relates to treating intestinal diseases and affecting intestinal metabolism with the drug conjugate.

  这项发明涉及一种药物结合物，包括药物和植物类固醇。该药物结合物可以将药物定位到肠细胞传递，因此可用于治疗疾病，包括肠道疾病，或影响肠道代谢。因此，该发明还涉及使用药物结合物治疗肠道疾病和影响肠道代谢。
• Novel sterol/stanol phosphorylnitroderivatives and use thereof in treating or preventing cardiovascular disease, its underlying conditions and other disorders
  申请人：Orchansky Liliana Patricia

  公开号：US20070232688A1

  公开（公告）日：2007-10-04

  Sterol and stanol phosphorylnitro derivatives and their use in treating or preventing cardiovascular disease, its underlying conditions and other disorders are disclosed. The disclosed compounds include a phosphate linker, at least one moiety that releases nitric oxide (NO), and a sterol or stanol moiety. Some compounds additionally include an ascorbyl moiety to make the compound more readily soluble in aqueous and non-aqueous media.

  甾醇和甾酚磷酸硝基衍生物及其在治疗或预防心血管疾病、其潜在病症和其他疾病中的用途被披露。所披露的化合物包括一个磷酸酯连接物、至少一个释放一氧化氮（NO）的基团，以及一个甾醇或甾酚基团。一些化合物还包括抗坏血酸基团，以使化合物在水性和非水性介质中更容易溶解。
• Aromatic amine derivative and use thereof
  申请人：Taniguchi Takahiko

  公开号：US20090325956A1

  公开（公告）日：2009-12-31

  The present invention provides a novel SCD inhibitor. An SCD inhibitor containing a compound represented by the formula [I] wherein ring A is an optionally substituted aromatic ring, ring B is an optionally substituted ring, ring C is an optionally substituted aromatic ring, R is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, and X is a spacer having 1 to 5 atoms in the main chain, or a salt thereof, or a prodrug thereof.

  本发明提供了一种新型SCD抑制剂。一种包含由下式[I]表示的化合物的SCD抑制剂 其中环A是可选择取代的芳香环，环B是可选择取代的环，环C是可选择取代的芳香环，R是氢原子，可选择取代的碳氢基团或可选择取代的杂环基团，X是具有主链中1到5个原子的间隔物，或其盐，或其前药。
• Carbon-linked substituted piperidines and derivatives thereof useful as histamine H3 antagonists
  申请人：Aslanian G. Robert

  公开号：US20070010513A1

  公开（公告）日：2007-01-11

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M 1 and M 3 are CH or N; M 2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH 2 ) q —, —C(═NOR 7 )— or —SO 1-2 —; Z is a bond or optionally substituted alkylene or alkenylene; R 1 is H, alkyl, alkenyl, or optionally substituted cycloalkyl, aryl, heteroaryl, heterocycloalkyl or a group of the formula: where ring A is a monoheteroaryl ring; R 1 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome nonalcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma or cognition deficit disorders using said compounds, alone or in combination with other agents.

  揭示了以下化合物的结构式或其药学上可接受的盐，其中： M1和M3为CH或N； M2为CH、CF或N； Y为—C(═O)—、—C(═S)—、—(CH2)q—、—C(═NOR7)—或—SO1-2—；Z为键或可选择地取代的烷基或烯基； R1为H、烷基、烯基，或可选择地取代的环烷基、芳基、杂芳基、杂环烷基或下式的基团： 其中环A为单杂芳基环； R1为可选择地取代的烷基、烯基、芳基、杂芳基、环烷基或杂环烷基；其余变量如规范中所定义；使用这些化合物，单独或与其他药剂结合，治疗过敏引起的气道反应、充血、肥胖、代谢综合征、非酒精性脂肪肝病、肝脂肪变性、非酒精性脂肪性肝炎、肝硬化、肝细胞癌或认知缺陷症状的组合物和治疗方法。
• Phenoxypiperidines and analogs thereof useful as histamine H3 antagonists
  申请人：Mutahi W. Mwangi

  公开号：US20070167435A1

  公开（公告）日：2007-07-19

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N; X is a bond, alkylene, —C(O)—, —C(N—OR 5 )—, —C(N—OR 5 )—CH(R 6 )—, —CH(R 6 )—C(N—OR 5 )—, —O—, —OCH 2 —, —CH 2 O— or —S(O) 0-2 —; Y is —O—, —(CH 2 ) 2 —, —C(═O)—, —C(═NOR 7 )— or —SO 0-2 —; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group; R 1 is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof; R 2 is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.

  揭示了以下化合物的结构式或其药学上可接受的盐或溶剂，其中：M为CH或N；U和W分别为CH，或者U和W中的一个为CH，另一个为N；X为键，烷基，—C(O)—，—C(N—OR5)—，—C(N—OR5)—CH(R6)—，—CH(R6)—C(N—OR5)—，—O—，—OCH2—，—CH2O—或—S(O)0-2—；Y为—O—，—(CH2)2—，—C(═O)—，—C(═NOR7)—或—SO0-2—；Z为键，可选择地取代的烷基或被杂原子或杂环基中断的烷基；R1为可选择地取代的烷基，环烷基，芳基，芳基烷基，杂芳基，杂环烷基或苯并咪唑基或其衍生物；R2为可选择地取代的烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基或杂环烷基；其余变量如规范中所定义；使用这些化合物，单独或与其他药剂联合使用，治疗由过敏引起的气道反应、充血、糖尿病、肥胖症、与肥胖有关的疾病、代谢综合征和认知缺陷障碍的组合物和方法。

表征谱图