alpha-[(6-O-beta-D-吡喃葡萄糖基-beta-D-吡喃葡萄糖基)氧基]-苯乙腈 | 51371-34-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: alpha-[(6-O-beta-D-吡喃葡萄糖基-beta-D-吡喃葡萄糖基)氧基]-苯乙腈
• 英文名称: amygdalin
• 英文别名: D-amygdalin；amygdaline；[(6-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy](phenyl)acetonitrile；2-phenyl-2-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyacetonitrile
• CAS: 51371-34-7
• 化学式: C₂₀H₂₇NO₁₁
• 分子量: 457.434
• InChiKey: XUCIJNAGGSZNQT-SWRVSKMJSA-N

物化性质

• 沸点：
  743.3±60.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)
• 熔点：
  223-226 °C
• 溶解度：
  VERY SOL IN HOT WATER; SLIGHTLY SOL IN ALCOHOL; INSOL IN ETHER, CHLOROFORM; SOL IN HOT ALCOHOL
• 旋光度：
  SPECIFIC OPTICAL ROTATION (WATER, C= 1): -42 DEG @ 20 °C/D; SADTLER REF NUMBER: 16450 (IR, PRISM); 5152 (UV)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  202
• 氢给体数：
  7
• 氢受体数：
  12

ADMET

代谢

苦杏仁苷是一种由葡萄糖、苯甲醛和氰化物组成的化学复合物，后者可以通过β-葡萄糖苷酶或乳化酶的作用释放出来。尽管这些酶在哺乳动物组织中不存在，但人类的肠道微生物群似乎拥有这些或类似的酶，能够促使氰化物的释放，导致人类中毒。因此，与静脉注射相比，通过口服途径摄入的苦杏仁苷可能毒性高达40倍。

AMYGDALIN IS A CHEMICAL COMBINATION OF GLUCOSE, BENZALDEHYDE, & CYANIDE FROM WHICH THE LATTER CAN BE RELEASED BY THE ACTION OF BETA-GLUCOSIDASE OR EMULSIN. ALTHOUGH THESE ENZYMES ARE NOT FOUND IN MAMMALIAN TISSUES, THE HUMAN INTESTINAL MICROFLORA APPEARS TO POSSESS THESE OR SIMILAR ENZYMES CAPABLE OF EFFECTING CYANIDE RELEASE RESULTING IN HUMAN POISONING. FOR THIS REASON AMYGDALIN MAY BE AS MUCH AS 40 TIMES MORE TOXIC BY THE ORAL ROUTE AS COMPARED WITH IV INJECTION.

来源:Hazardous Substances Data Bank (HSDB)

代谢

植物苷类通过酶促或酸性水解产生氰化物，以及糖和芳香醛。常见的例子是苦杏仁中的苦杏仁苷（龙胆二糖+苯甲醛+氢氰酸）。在植物组织中，与苷类共存的一种酶复合物，乳糖酶，催化苷类的水解，首先转化为mandelonitrile或p-羟基mandelonitrile，然后转化为苯甲醛或p-羟基苯甲醛和氢氰酸。这些醛被氧化成相应的芳香酸，并以肽结合物的形式排出体外。

...PLANT GLYCOSIDES ARE CHARACTERIZED BY PRODN OF CYANIDE, TOGETHER WITH A SUGAR & AROMATIC ALDEHYDE, ON ENZYMIC OR ACID HYDROLYSIS. COMMON EXAMPLES ARE AMYGDALIN (GENTIOBIOSE + BENZALDEHYDE + HCN) WHICH IS PRESENT IN BITTER ALMONDS... AN ENZYME COMPLEX, EMULSIN, IS PRESENT TOGETHER WITH GLYCOSIDES IN PLANT TISSUES & CATALYZES THE HYDROLYSIS OF GLYCOSIDES, FIRST TO MANDELONITRILE OR P-HYDROXYMANDELONITRILE, & THEN TO BENZALDEHYDE OR P-HYDROXYBENZALDEHYDE, & HCN. ... THE ALDEHYDES ARE OXIDIZED TO CORRESPONDING AROMATIC ACIDS & EXCRETED AS PEPTIDE CONJUGATES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

各种李属植物含有...苦杏仁苷，它可以通过酶类乳化酶水解...在完整的植物中不会发生此类反应；只有在植物组织受损或开始腐烂时，才会开始释放氢氰酸。

...VARIOUS PRUNUS SPECIES CONTAIN...AMYGDALIN, WHICH IS HYDROLYZED BY ENZYME EMULSIN... IN INTACT PLANT NO SUCH ACTION TAKES PLACE; IT IS NOT UNTIL PLANT TISSUE IS DAMAGED OR STARTS TO DECAY THAT LIBERATION OF HCN BEGINS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

糖苷的分解在瘤胃中通常比单胃动物的消化道更容易或更快发生。此外，小分子可以在瘤胃被吸收，从而迅速进入循环。来自蔷薇科成员的氰苷糖苷，如苦杏仁苷的分解就是一个例子。

BREAKDOWN /OF GLYCOSIDES/ OFTEN OCCURS MORE READILY OR MORE RAPIDLY IN RUMEN THAN IN DIGESTIVE TRACT OF MONOGASTRIC ANIMALS. ALSO, SMALL MOLECULES CAN BE ABSORBED AT THE RUMEN & THUS ENTER CIRCULATION RAPIDLY. BREAKDOWN OF CYANOGENIC GLYCOSIDES, SUCH AS AMYGDALIN, FROM MEMBERS OF ROSE FAMILY...IS AN EXAMPLE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

两例苦杏仁苷（杏仁苷）毒性报告，一例为48岁患有淋巴瘤的女性，另一例为46岁患有大细胞未分化肺癌的男性。女性患者在接受每周6毫克静脉注射和每日三次500毫克口服给药后，出现了发热、不适、头痛、严重腹部绞痛、弥漫性斑疹样红斑皮疹、淋巴结病和肝脾肿大。男性患者在每日口服500毫克苦杏仁苷后，出现了双下肢和上肢的进行性神经肌肉无力。两例由于口服给药引起的毒性在停药后均得到解决。

TWO CASES OF LAETRILE (AMYGDALIN) TOXICITY WERE REPORTED IN A 48-YR-OLD WOMAN WITH LYMPHOMA & A 46-YR-OLD MAN WITH A LARGE CELL ANAPLASTIC CARCINOMA OF THE LUNG. THE WOMAN EXHIBITED FEVER, MALAISE, HEADACHE, SEVERE ABDOMINAL CRAMPS, A DIFFUSE MACULAR ERYTHEMATOUS RASH, LYMPHADENOPATHY & HEPATOSPLENOMEGALY FOLLOWING A WEEKLY 6 MG IV INJECTION & 5OO MG 3 TIMES DAILY ORALLY. THE MAN PRESENTED WITH PROGRESSIVE NEUROMUSCULAR WEAKNESS OF BOTH LOWER & UPPER EXTREMITIES FOLLOWING ORAL ADMIN OF 500 MG OF AMYGDALIN DAILY. BOTH CASES OF TOXICITY RESULTING FROM ORAL ADMIN WAS RESOLVED FOLLOWING DISCONTINUATION OF THE DRUG.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

一位57岁患有乳腺癌的女性因摄入致死剂量的苦杏仁苷（杏仁苷）被送医。入院时，她的氰化物水平为29.0微克/分升。患者在接受对症治疗后有所好转，并被转移到另一家医院，三天后出院。十二天后，患者无生命迹象返回急诊科。尸检显示氰化物水平为218微克/分升，并记录死亡原因为氰化物中毒。

A FATAL LAETRILE (AMYGDALIN) INGESTION BY A 57-YR-OLD FEMALE WITH BREAST CARCINOMA WAS PRESENTED. CYANIDE LEVEL ON ADMISSION TO HOSPITAL WAS 29.0 MCG/DL. THE PT IMPROVED WITH SYMPTOMATIC THERAPY & WAS TRANSFERRED TO ANOTHER HOSPITAL FROM WHICH SHE WAS DISCHARGED 3 DAYS LATER. TWELVE DAYS LATER, THE PT WAS RETURNED TO THE EMERGENCY DEPARTMENT WITH NO SIGN OF LIFE. AN AUTOPSY REVEALED A CYANIDE LEVEL OF 218 MCG/DL & DOCUMENTED THE CAUSE OF DEATH AS CYANIDE POISONING.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

一起氰化物中毒的近致命案例被报告，发生在一名48岁的女性身上，此前她接受了为期9天的苦杏仁苷（杏仁苷）治疗。苦杏仁苷通过静脉、肌肉注射、口服和灌肠的方式给药，并伴随“解毒饮食”。入院时血液中氰化物水平为116微克/分升。

A NEAR FATAL CASE OF CYANIDE POISONING IS REPORTED IN A 48-YR-OLD WOMAN AFTER A 9 DAY COURSE OF LAETRILE (AMYGDALIN). LAETRILE WAS ADMIN IV, IM, ORALLY, & RECTALLY ALONG WITH A "DETOXIFICATION DIET". BLOOD LEVELS OF CYANIDE ON ADMISSION WERE 116 MUG/DL.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

两起儿童苦杏仁苷中毒事件在食用杏核后发生。第一起事件涉及8名儿童，在大量摄入后2小时表现出典型的苦杏仁苷中毒迹象和症状；其中7名儿童康复，1名儿童死亡。第二起事件涉及16名儿童，他们食用了用杏核制成的糖果。症状和体征与第一组相同，但在摄入后半小时出现，并且非常严重。其中三名儿童死亡。

TWO EPISODES OF CYANIDE POISONING OCCURRED IN CHILDREN AFTER INGESTION OF APRICOT KERNELS. THE 1ST EPISODE INVOLVED 8 CHILDREN WHO EXHIBITED TYPICAL SIGNS & SYMPTOMS OF CYANIDE POISONING 2 HR AFTER INGESTION OF LARGE AMOUNTS; 7 CHILDREN RECOVERED & 1 DIED. THE 2ND EPISODE INVOLVED 16 CHILDREN WHO HAD EATEN SWEETS PREPARED FROM KERNELS. SYMPTOMS & SIGNS WERE THE SAME AS THOSE IN THE 1ST GROUP BUT APPEARED 1/2 HR AFTER INGESTION & WERE VERY SEVERE. THREE OF THE CHILDREN DIED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

苦杏仁苷是由葡萄糖、苯甲醛和氰化物组成的化学复合物，后者可以释放出来...苦杏仁苷是苦杏仁素的主要成分，这种据称具有抗癌作用的药物也曾导致人类氰化物中毒。

AMYGDALIN IS A CHEMICAL COMBINATION OF GLUCOSE, BENZALDEHYDE, & CYANIDE FROM WHICH THE LATTER CAN BE RELEASED... AMYGDALIN IS THE MAJOR INGREDIENT OF LAETRILE, & THIS ALLEGED ANTICANCER DRUG HAS ALSO BEEN RESPONSIBLE FOR HUMAN CYANIDE POISONING.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

苦杏仁苷口服给药后小鼠体内最高氰化物水平在大约1.5-2小时达到，并且与氰化钾给药后的值范围相似。评估了消化道各个区域内容物以及肿瘤组织从苦杏仁苷中释放氰化物的能力。胃和上肠的活动很少，而下半肠和粪便释放了大量的氰化物。小鼠之间的差异很大。

THE MAX CYANIDE LEVEL AFTER ORAL ADMIN OF AMYGDALIN TO MICE WAS REACHED AT ABOUT 1 1/2-2 HR & WAS WITHIN THE RANGE OF VALUES SEEN AFTER KCN ADMIN. THE ABILITY OF THE CONTENTS OF VARIOUS REGIONS OF THE GI TRACT & OF TUMOR TISSUE TO RELEASE CYANIDE FROM AMYGDALIN WAS ASSESSED. THE STOMACH & UPPER INTESTINE HAD LITTLE ACTIVITY WHILE THE LOWER INTESTINE & FECES RELEASED LARGE AMOUNTS. THERE WAS A LARGE VARIATION BETWEEN MICE.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  alpha-[(6-O-beta-D-吡喃葡萄糖基-beta-D-吡喃葡萄糖基)氧基]-苯乙腈 在 [PtH(PMe₂OH)((PMe₂O_...H_...OPMe₂)] 水 作用下， 反应 4.0h， 以98%的产率得到2-phenyl-2-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}methyl)tetrahydro-2H-pyran-2-yl]oxy}acetamide
  参考文献：
  名称：

  Platinum-Catalyzed Selective Hydration of Hindered Nitriles and Nitriles with Acid- or Base-Sensitive Groups

  摘要：

  Hindered tertiary nitriles can be hydrolyzed under neutral and mild conditions to the corresponding amides using platinum(II) catalysts with dimethylphosphine oxide or other secondary phosphine oxides (SPOs, phosphinous acids) as ligands. We have found that this procedure also works well for nitriles with acid- or base-sensitive groups, which is unprecedented in terms of yield and selectivity. The catalyst loading can be as low as 0.5 mol %. Amides are isolated as the only product in high yield, and no further hydrolysis to the corresponding acids takes place. Reactions are carried out at 80 degreesC but take place even at room temperature. When enantiopure secondary phosphine oxide ligands are used in the hydrolysis of racemic nitriles, no kinetic resolution is observed, presumably due to racemization of the ligand during the reaction.

  DOI：

  10.1021/jo035487j
• 作为产物：
  描述：

  [(2R,3S,4R,5R,6R)-6-[[(2R,3S,4R,5R,6R)-6-[[(R)-cyano(phenyl)methoxy]methyl]-3,4,5-trihydroxyoxan-2-yl]methoxy]-3,4,5-trihydroxyoxan-2-yl] (E)-3-(4-hydroxyphenyl)prop-2-enoate 生成 alpha-[(6-O-beta-D-吡喃葡萄糖基-beta-D-吡喃葡萄糖基)氧基]-苯乙腈
  参考文献：
  名称：

  NAHRSTEDT, ADOLF;SATTAR, ESSAM ABDEL;EL-ZALABANI, SOHEIR M. H., PHYTOCHEMISTRY, 29,(1990) N, C. 1179-1181

  摘要：

  DOI：

文献信息

• [EN] NOVEL EP4 AGONISTS AS THERAPEUTIC COMPOUNDS<br/>[FR] NOUVEAUX AGONISTES DES RÉCEPTEURS EP4 UTILISÉS COMME COMPOSÉS THÉRAPEUTIQUES
  申请人：ALLERGAN INC

  公开号：WO2015188152A1

  公开（公告）日：2015-12-10

  Described herein are compounds that are EP4 agonists and antagonists which are useful for treating a variety of pathological conditions associated with activity of EP4 receptors.

  描述了EP4激动剂和拮抗剂化合物，这些化合物用于治疗与EP4受体活性相关的多种病理状况。
• BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
  申请人：SENOMYX, INC.

  公开号：US20160376263A1

  公开（公告）日：2016-12-29

  The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.

  本发明涵盖已知用于改变苦味感知的化合物和组合物，以及所述组合物和化合物与额外的组合物、化合物和产品的组合。示例组合物包括以下一种或多种：冷却剂；无活性药物成分；活性药用成分；食品添加剂或食品；调味剂或调味增强剂；食品或饮料产品；苦味化合物；甜味剂；苦味剂；酸味调味剂；咸味调味剂；鲜味调味剂；植物或动物产品；已知用于宠物护理产品中的化合物；已知用于个人护理产品中的化合物；已知用于家用产品中的化合物；制药制剂；局部制剂；大麻衍生或与大麻相关的产品；已知用于口腔护理产品中的化合物；饮料；香味、香水或除臭剂；已知用于消费品中的化合物；硅化合物；磨料；表面活性剂；发热剂；吸烟物品；脂肪、油脂或乳化剂；和/或益生菌或补充剂。
• USE OF 3-(3-HYDROXY-4-METHOXY-PHENYL)-1-(2,4,6-TRIHYDROXY-PHENYL) PROPAN-1-ONE
  申请人：SYMRISE AG

  公开号：US20190343777A1

  公开（公告）日：2019-11-14

  The present invention concerns the use of 3-(3-Hydroxy-4-methoxy-phenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one for masking, reducing or suppressing an unpleasant taste impression, preferably bitter, sour and/or astringent taste impression of unpleasant-tasting substances or mixture of substances, preferably bitter-, sour-, and/or astringent-tasting substances or mixtures of substances, and in particular the bitter taste impression of bitter-tasting substances, and/or modulating the taste impressions selected from the group consisting of cooling, umami, fruity and spicy notes of cooling-, umami-, fruity- or spicy-tasting substances or mixture of substances, and simultaneously intensifying the sweet-taste impression of sweet-tasting substances or mixtures of substances or both sweet- and bitter-tasting tasting substances or mixture of substances.

  本发明涉及使用3-(3-羟基-4-甲氧基苯基)-1-(2,4,6-三羟基苯基)丙酮来掩盖、减少或抑制令人不愉快的味觉印象，优选是苦、酸和/或涩的不愉快味觉印象的不愉快味道物质或物质混合物，优选是苦味、酸味和/或涩味物质或物质混合物，特别是苦味物质的苦味印象，和/或调节选自冷却、鲜味、果味和辛辣味的味觉印象的味道物质或物质混合物，同时增强甜味物质或物质混合物或甜味和苦味物质或物质混合物的甜味印象。
• THERAPEUTIC AGENTS
  申请人：Allergan, Inc.

  公开号：US20140323558A1

  公开（公告）日：2014-10-30

  The invention provides well-defined compounds that are either EP 2 agonists, EP 4 agonists, or mixed EP 2 /EP 4 agonist. The compounds are useful for treating a variety of pathological conditions associated with activity of the EP 2 and/or EP 4 receptors.

  这项发明提供了明确定义的化合物，它们要么是EP2激动剂，EP4激动剂，或混合的EP2/EP4激动剂。这些化合物对治疗与EP2和/或EP4受体活性相关的各种病理条件是有用的。
• Immunomodulating beta-1,6-D-glucans
  申请人：Innate Biotherapeutics, LLC

  公开号：US10266609B2

  公开（公告）日：2019-04-23

  This invention relates to modifications of β-1,6-D-glucans, e.g., structures according to Formula (I), and the ability of these compositions to modulate an immune response.

  这项发明涉及对β-1,6-D-葡聚糖的修饰，例如，符合式（I）的结构，以及这些组合物调节免疫反应的能力。