(2S)-2-氨基-3-[(1S)-2-亚甲基环丙基]丙酸 | 156-56-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2S)-2-氨基-3-[(1S)-2-亚甲基环丙基]丙酸
• 中文别名: (1R,αS)-α-氨基-2-亚甲基环丙烷丙酸
• 英文名称: (2S,4R)-hypoglycin A
• 英文别名: (2S,4R) α-<(methylenecyclopropyl)methyl>glycine；hypoglycin；hypoglycin A；(2S)-2-azaniumyl-3-[(1R)-2-methylidenecyclopropyl]propanoate
• CAS: 156-56-9
• 化学式: C₇H₁₁NO₂
• 分子量: 141.17
• InChiKey: OOJZCXFXPZGUBJ-RITPCOANSA-N

物化性质

• 熔点：
  >200°C (dec.)
• 比旋光度：
  D32 +9.2°
• 沸点：
  258.21°C (rough estimate)
• 密度：
  1.1522 (rough estimate)
• 颜色/状态：
  Yellow plates from methanol + water
• 旋光度：
  Specific optical rotation at 32 °C for D (sodium) line = +9.2 deg.
• 分解：
  When heated to decomposition it emits toxic fumes of /nitric oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

转氨基作用导致亚甲基环丙烷丙酮酸的形成，后者通过脱羧反应转变为亚甲基环丙烷乙酸；磷酸吡哆醛加上镁(2+)离子和硫胺素焦磷酸，镁(2+)离子加上辅酶A是这两个反应步骤中涉及的辅因子。

TRANSAMINATION RESULTS IN FORMATION OF METHYLENECYCLOPROPANEPYRUVIC ACID, WHICH UNDERGOES DECARBOXYLATION TO METHYLENECYCLOPROPANE ACETIC ACID; PYRIDOXAL PHOSPHATE PLUS MG(2+) IONS AND THIAMINE PYROPHOSPHATE, MG(2+) IONS PLUS COENZYME-A ARE THE COFACTORS INVOLVED IN THE TWO REACTION STEPS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大量异常代谢物在服用低糖酸的大鼠尿液中被发现...分析。其中十种之前并未与低糖酸给药相关联：包括几种羟基化合物，来自缬氨酸和异亮氨酸途径的化合物，2-氧代己二酸、n-丁酰甘氨酸和异戊酰葡萄糖苷酸。这些结果表明，异亮氨酸和缬氨酸代谢途径在其各自的酰基辅酶A脱氢步骤受到抑制，正如之前所展示的脂肪酸、亮氨酸和赖氨酸代谢途径的情况。

Numerous abnormal metabolites were identified in large amounts in the urine of hypoglycin-treated rats... . analysis. ... Ten of them have not been previously associated with hypoglycin administration: these are several hydroxy compounds, including those from the valine and isoleucine pathways, 2-oxo-adipic acid, n-butyrylglycine and isovaleryl glucuronide. These results indicate that the pathways of isoleucine and valine metabolism are inhibited at their respective acyl-CoA dehydrogenation steps, as is the case for fatty acid, leucine and lysine metabolism, as previously shown.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 14C- 和 3H-标记的软脂酸与低糖素一起给予大鼠，并在尿中的二羧酸中测量放射性。两种同位素都结合到了己二酸和癸二酸中，表明了前体与产物之间的关系。戊二酸基本上未标记。相对于软脂酸的C-1，C-16的优先结合可以被推断出来。因此，似乎脂肪酸的ω-氧化主要发生在链缩短的中期阶段，此时低糖素对β-氧化的抑制作用变得更加明显。

... 14C- and 3H-labelled palmitic acid was administered with hypoglycin to rats, and radioactivity was measured in urinary dicarboxylic acids... . Both isotopes were incorporated into adipic and sebacic acids, indicating a precursor-product relationship. Glutaric acid was, essentially, unlabelled. Preferential incorporation of C-16, relative to C-1 of palmitate ... could be deduced ... . It thus appears that omega-oxidation of the fatty acid intervenes predominantly at an intermediate stage of chain-shortening, when inhibition of beta-oxidation by hypoglycin becomes more pronounced.

来源:Hazardous Substances Data Bank (HSDB)

代谢

低血糖素A，现在简称为低血糖素，通过转氨作用和氧化脱羧作用代谢成亚甲基环丙基醋酸（MCPA）。

Hypoglycin A, which is now simply called hypoglycin, is metabolized by means of transamination and oxidative decarboxylation to methylene cyclopropyl acetic acid (MCPA).[

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

对禁食的大鼠进行标准饮食并在其体内注射 Hypoglycin，会导致严重的虚弱、体温下降和大量的二羧酸尿。在含有克洛贝特（clofibrate）的饮食中喂养的大鼠，在注射 Hypoglycin 后看起来正常，但仍然出现了明显的二羧酸尿，不过程度比标准饮食喂养的大鼠轻。在大鼠体内注射 Hypoglycin、丁酰辅酶 A（butyryl-CoA）和癸酰辅酶 A（decanoyl-CoA），但不是棕榈酰辅酶 A（palmitoyl-CoA）后，标准饮食喂养的大鼠肝脏中的脱氢酶活性被强烈抑制（80-95%）。克洛贝特喂养减少了这些脱氢酶的抑制，抑制率降至大约 40-60%。因此得出结论，尽管克洛贝特可以防止 Hypoglycin 的毒性作用，但由二羧酸尿所表明的某些酶的抑制作用只是部分被预防。

... Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria. Rats maintained on a diet containing clofibrate appeared normal after injection of hypoglycin, but had a marked dicarboxylic aciduria which was less than that induced in rats on a normal diet. After administration of hypoglycin, butyryl-CoA and decanoyl-CoA, but not palmitoyl-CoA, dehydrogenase activities were strongly inhibited (80-95%) in the livers of animals on a standard diet. Clofibrate feeding decreased the inhibition of these dehydrogenases to about 40-60%. It was concluded that although clofibrate protects against the toxic effects of hypoglycin, some enzyme inhibitions as indicated by dicarboxylic aciduria are only partly prevented.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

...氯贝丁酯饲养显然保护了动物免受低血糖素的有毒、降糖和降体温的影响...并完全防止了低血糖素引起的超微结构损伤。在低血糖素给药后，肝脏线粒体丁酰辅酶A脱氢酶活性被抑制了超过90%，令人惊讶的是，研究的过氧化物酶体酶的活性在很大程度上得到了保留。当低血糖素给予食用含有氯贝丁酯饮食的大鼠时，单独低血糖素治疗后的癸酰肉碱氧化是不完全的，在解耦线粒体中仍然不完全，但在耦合线粒体中显然变得完全。在后一种情况下，在氧气摄取脉冲的最后四分之一期间，速率有所减慢。此外，氯贝丁酯饲养的动物中，丁酰辅酶A脱氢酶活性受到低血糖素的影响要小得多。...

...Clofibrate feeding apparently protected the animals against the toxic, hypoglycemic and hypothermic effects of hypoglycin...and completely prevented the ultrastructural damage caused by hypoglycin. After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved. When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria. In the latter condition, there was a slowing of the rate during the last quarter of the pulse of oxygen uptake. Further, butyryl-CoA dehydrogenase activity was much less affected by hypoglycin in clofibrate-fed animals. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

向注射了Hypoglycin（150毫克/千克，IP）的大鼠中给予甘氨酸（75毫克/千克，IP）可以预防死亡、低血糖和体温过低，并且大大减少血浆中异戊酸加2-甲基丁酸、丁酸和环丙烯乙酸的浓度上升，后者是Hypoglycin代谢的终产品。

ADMIN OF GLYCINE (75 MG/KG, IP) TO RATS INJECTED WITH HYPOGLYCIN (150 MG/KG, IP) PREVENTED DEATH, HYPOGLYCEMIA, AND HYPOTHERMIA AND GREATLY DECR THE RISE IN PLASMA CONCN OF ISOVALERATE PLUS 2-METHYLBUTYRATE, BUTYRATE, AND METHYLENECYCLOPROPYLACETATE, AN END PRODUCT OF HYPOGLYCIN METAB.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

治疗主要包括胃肠去污和支持性护理。在对症状患者或成人有意大量摄入的情况下，应给予活性炭。对于意识水平降低和呼吸抑制的患者，可能需要呼吸支持。应提供一般的支持性护理，以治疗低血糖、低血压和心律失常。/中枢神经系统抑制剂植物/

Treatment consists primarily of gastrointestinal decontamination and supportive care. ... In symptomatic patients or in adults with large intentional ingestions, activated charcoal should be administered. Respiratory support may be required in patients with depressed levels of consciousness and respiratory depression. General supportive care should be provided for treatment of hypoglycemia, hypotension and dysrhythmias. /CNS Depressant Plants/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2922499990

反应信息

• 作为产物：
  描述：

  (2S,4RS)-2-hydroxy-4-phenylsulfonyl-5-trimethylsilyl-1-pentyl p-toluenesulfonate 在 吡啶 、 盐酸 、 lithium hydroxide 、 正丁基锂 、 四丁基氟化铵 、 potassium carbonate 、 对甲苯磺酰氯 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醚 、 正己烷 、 水 为溶剂， 反应 121.92h， 生成 (2S)-2-氨基-3-[(1S)-2-亚甲基环丙基]丙酸
  参考文献：
  名称：

  低血糖素A的各个非对映异构体的不对称全合成。

  摘要：

  利用Sharpless环氧化法合成了构成非寻常的含有α-氨基酸次糖苷A的不寻常的亚甲基环丙烷的各个非对映异构体，以允许不对称的亚甲基环丙烷的合成。

  DOI：

  10.1016/s0040-4020(01)89313-3

文献信息

• Asymmetric total synthesis of the individual diastereoisomers of hypoglycin A
  作者：Jack E. Baldwin、Robert M. Adlington、David Bebbington、Andrew T. Russell

  DOI：10.1039/c39920001249

  日期：——

  The individual diastereoisomers that constitute the unusual methylenecyclopropane containing α-amino acid hypoglycin A have been synthesised utilising the Sharpless epoxidation to permit an asymmetric methylene cyclopropane synthesis.

  利用Sharpless环氧化法合成了构成非寻常的含有α-氨基酸次糖苷A的不寻常的亚甲基环丙烷的各个非对映异构体，以允许不对称的亚甲基环丙烷的合成。
• GLYCERO-COMPOUND HAVING TRIPLE BOND AND MEMBRANE MATERIAL CONTAINING THE SAME
  申请人：BABA Teruhiko

  公开号：US20070105823A1

  公开（公告）日：2007-05-10

  The present invention provides a chemically stable and novel glycero-compound having one or two triple bonds, one molecule of a glycerol and one or two molecules of a fatty alcohol having a triple bond being linked through an ether bond, an organic group being linked to residual hydroxyl groups of the glycerol, which can be used as a membrane material for forming a vesicle membrane due to its high intermolecular cohesive force, and also provides a membrane forming material containing the same. The glycero-compound has a triple bond represented by the following general formula (1): wherein n and m each represents a number of 1 to 17 and the total (n+m) is a number of 4 to 18, n and m may be the same or different, and R represents a hydrogen atom, a metal atom, a phosphoric acid group, or an organic group which may be linked through a phosphoric acid group.

  本发明提供了一种化学稳定且新颖的甘油化合物，其中含有一个或两个三键，一个甘油分子和一个或两个含有三键的脂肪醇分子通过醚键连接，有机基与甘油的残余羟基连接，由于其高分子间内聚力可用作形成囊泡膜的膜材料，还提供了含有相同物质的膜形成材料。该甘油化合物具有以下一般式（1）所代表的三键：其中n和m分别表示1到17之间的数字，总数（n+m）为4到18之间的数字，n和m可以相同也可以不同，R表示氢原子、金属原子、磷酸基或可以通过磷酸基连接的有机基。
• DELIVERY OF NUCLEIC ACID COMPLEXES FROM MATERIALS INCLUDING NEGATIVELY CHARGED GROUPS
  申请人：McGonigle Joseph Schmidt

  公开号：US20090263449A1

  公开（公告）日：2009-10-22

  Embodiments of the invention include devices and methods for the controlled elution of nucleic acid delivery complexes. In an embodiment, the invention includes a medical device including a substrate surface, a polymeric coating disposed on the surface, the polymeric coating coupled to the substrate surface through the reaction product of a photoreactive group; the polymeric coating comprising negatively charged species on the surface; and a plurality of nucleic acid delivery complexes disposed on the polymeric coating, the nucleic acid delivery complexes comprising a nucleic acid and a cationic carrier agent complexed to the nucleic acid. Other embodiments are included herein.

  本发明的实施例包括用于控制核酸递送复合物释放的装置和方法。在一种实施例中，本发明包括一种医疗器械，其中包括基底表面、沉积在表面上的聚合物涂层，聚合物涂层通过光反应性基团的反应产物与基底表面耦合；聚合物涂层在表面上包含负电荷物种；以及多个核酸递送复合物沉积在聚合物涂层上，核酸递送复合物包括与核酸形成复合物的阳离子载体剂。本发明还包括其他实施例。
• Coatings with crystallized active agent(s) and methods
  申请人：Chappa A. Ralph

  公开号：US20060134168A1

  公开（公告）日：2006-06-22

  The present invention relates to coatings with crystallized active agent(s) and related methods. In an embodiment, the invention includes a method for coating a medical device including selecting a solvent and a polymer, selecting a concentration of an active agent of at least a certain amount of saturation, forming a coating composition having the selected concentration of the active agent, and applying the coating composition to the medical device. In an embodiment, the invention includes an elution control coating disposed on a medical device, the elution control coating including a polymer, and an active agent, wherein the active agent is at least about 80% crystallized within one week of being disposed on the medical device. In an embodiment, the invention includes a method for enhancing the formation of active agent crystals within a coating layer including forming a coating solution and adjusting the concentration of the active agent in the coating solution to reach some percentage of the active agent saturation point. In an embodiment, the invention includes a method of enhancing crystallization of an active agent, the method including forming a coating solution comprising a polymer, an active agent, and a solvent; applying the coating solution to a substrate; and increasing the rate of active agent nucleation within the coating.

  本发明涉及具有结晶活性剂的涂层及相关方法。在一种实施例中，本发明包括一种涂覆医疗器械的方法，包括选择溶剂和聚合物，选择至少一定饱和度的活性剂浓度，形成具有所选活性剂浓度的涂层组合物，并将涂层组合物涂覆在医疗器械上。在一种实施例中，本发明包括在医疗器械上设置的控制释放涂层，该控制释放涂层包括聚合物和活性剂，其中活性剂在被设置在医疗器械上的一周内至少约80%结晶。在一种实施例中，本发明包括一种增强涂层层内活性剂晶体形成的方法，包括形成涂层溶液并调整涂层溶液中活性剂的浓度以达到活性剂饱和点的一定百分比。在一种实施例中，本发明包括一种增强活性剂结晶的方法，该方法包括形成包括聚合物、活性剂和溶剂的涂层溶液；将涂层溶液涂覆在基底上；并增加涂层内活性剂成核的速率。
• COATINGS WITH CRYSTALLIZED ACTIVE AGENT(S) AND METHODS
  申请人：Chappa Ralph A.

  公开号：US20100093686A1

  公开（公告）日：2010-04-15

  Coatings with crystallized active agent(s) and related methods are disclosed. One method includes selecting a solvent and a polymer, selecting a concentration of an active agent of at least a certain amount of saturation, forming a coating composition having the selected concentration of the active agent, and applying the coating composition to the medical device. Also disclosed is an elution control coating which includes active agent that is at least about 80% crystallized within one week of being disposed on a medical device. One method enhances the formation of active agent crystals within a coating layer by adjusting the concentration of the active agent in the coating solution to reach some percentage of the active agent saturation point. Another method includes increasing the rate of active agent nucleation within the coating.

  本发明涉及含晶化活性剂的涂层及其相关方法。其中一种方法包括选择溶剂和聚合物，选择至少达到一定饱和度的活性剂浓度，形成具有所选活性剂浓度的涂层组合物，并将涂层组合物应用于医疗器械上。本发明还涉及一种控制溶出的涂层，其中包括至少在被放置在医疗器械上的一周内晶化约80％的活性剂。一种方法通过调整涂层溶液中活性剂的浓度以达到一定比例的活性剂饱和点来增强涂层层内活性剂晶体的形成。另一种方法包括增加涂层内活性剂成核的速率。