11-去氧代介藜芦碱 beta-D-葡糖苷 | 23185-94-6

• 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: 11-去氧代介藜芦碱 beta-D-葡糖苷
• 中文别名: 11-去氧代介藜芦碱beta-D-葡糖苷
• 英文名称: cycloposine
• 英文别名: (2R,3R,4S,5S,6R)-2-[(3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3',6',10,11b-tetramethylspiro[2,3,4,6,6a,6b,7,8,11,11a-decahydro-1H-benzo[a]fluorene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 23185-94-6
• 化学式: C₃₃H₅₁NO₇
• 分子量: 573.77
• InChiKey: OSOOWXRUSUHLOX-PBFVMIKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  41
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  121
• 氢给体数：
  5
• 氢受体数：
  8

ADMET

代谢

孵化小鸡的畸形是通过将1-2毫克的环巴胺直接应用于开窗鸡胚的胚胎盾产生的。这表明环巴胺的母体代谢改变并非必要。/环巴胺/

Malformations in hatched chicks were produced by direct application of 1-2 mg of cyclopamine to the embryonic shield of windowed chicken eggs. This showed that maternal metabolic alteration of cyclopamine was not necessary. /Cyclopamine/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

几种藜芦属植物的物种与人类和动物的毒性有关。主要毒素是甾体生物碱；有些具有修改后的甾体模板，而其他则在于它们的酯化酸部分不同。这些生物碱通过增加神经细胞钠通道的通透性，使它们持续放电。与迷走神经相关联的刺激增加导致被称为贝佐尔德-雅里施反射的三联反应：低血压、心动过缓和呼吸暂停。临床上，各种藜芦提取物被作为抗高血压药物上市，但由于治疗指数狭窄而被撤出市场。摄入藜芦生物碱后，预期的体征和症状包括呕吐和腹痛，随后出现心血管效应，如心动过缓、低血压和心脏传导异常甚至死亡。其他哺乳动物摄入这些生物碱后也会出现类似的症状；食用藜芦加州种的动物胎儿可能会出现致畸效应。治疗包括支持性护理，重点是使用液体置换、阿托品和血管加压药来维持血流动力学稳定。症状出现时间在30分钟到4小时之间，病程可能从1天到10天不等；然而，在及时的支持性护理下，患者通常在24小时内完全恢复。

Several species of the Veratrum genus are associated with toxicity in humans and animals. The principal toxins are steroid alkaloids; some have a modified steroid template, whereas others differ in their esterified acid moieties. These alkaloids act by increasing the permeability of the sodium channels of nerve cells, causing them to fire continuously. Increased stimulation, associated with the vagal nerve results in a reflex that causes the triad of responses known as the Bezold-Jarisch reflex: hypotension, bradycardia and apnea. Clinically, various Veratrum extracts were marketed for use as antihypertensive drugs, but because of their narrow therapeutic index were withdrawn from the market. Following the ingestion of Veratrum alkaloids, expected signs and symptoms include vomiting and abdominal pain, followed by cardiovascular effects such as bradycardia, hypotension and cardiac conduction abnormalities and death. Similar symptoms arise in other mammalian species ingesting these alkaloids; teratogenic effects may occur to the fetuses of animals that have grazed on Veratrum californicum. Treatment consists of supportive care, with an emphasis on hemodynamic stability with fluid replacement, atropine and vasopressors. The onset of symptoms occurs between 30 minutes and 4 hours, and the duration of the illness can range from 1 to 10 days; however, with prompt supportive care, patients typically make a full recovery within 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

独眼畸形和与之相关的先天性畸形在爱达荷州的羊中很常见。正常的偏离包括单一或双重的眼球独眼畸形，上颚短小以及下颚突出和弯曲，偶尔在上眼皮上方有一个被皮肤覆盖的长鼻。加州藜芦植物在母羊怀孕第14天摄入时会引起这种状况。对怀孕的羊进行了多种藜芦生物碱的致畸性测试。独眼素（Cycloposine）产生的畸形与自然病例相似。

...CYCLOPIA AND RELATED CONGENITAL DEFORMITIES IN SHEEP WERE COMMON IN IDAHO. ... DEVIATIONS FROM NORMAL INCLUDED A SINGLE OR DOUBLE GLOBE CYCLOPIA AND SHORTENED UPPER JAW AND PROTRUDING AND CURVED LOWER JAW, OCCASIONALLY WITH ...SKIN-COVERED PROBOSCIS ABOVE THE SINGLE EYE. ... VERATRUM CALIFORNICUM CAUSED THE CONDITION WHEN PREGNANT EWES INGESTED IT ON GESTATION DAY 14. ... A NUMBER OF VERATRUM ALKALOIDS WERE TESTED IN PREGNANT SHEEP FOR TERATOGENICITY. ...CYCLOPOSINE PRODUCED DEFORMITIES SIMILAR TO NATURAL CASES.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

假鹅膏，包括白藜芦（Veratrum album）、绿藜芦（V. viride）和加州藜芦（V. californicum），含有多种生物碱，具有与商业产品藜芦碱类似的性质...白藜芦（白鹅膏）的根茎据说含有原藜芦碱，以及...加尔维碱、卢比加尔维碱、伪加尔维碱、藜芦洛定碱和藜芦白定碱。藜芦碱及相关生物碱的中毒症状包括流涎、腹泻、呕吐（甚至在牛中），多尿，兴奋后继以虚脱，脉搏微弱而不规则，呼吸深而慢，最终在抽搐或麻痹后死亡。/藜芦碱及相关生物碱/

THE FALSE HELLEBORES, INCL VERATRUM ALBUM, V VIRIDE & V CALIFORNICUM, CONTAIN VARIETY OF ALKALOIDS HAVING SIMILAR PROPERTIES TO THE COMMERCIAL PRODUCT, VERATRINE... THE RHIZOME OF V ALBUM (WHITE HELLEBORE) IS SAID...TO CONTAIN...PROTOVERATRINE, TOGETHER WITH...JERVINE, RUBIJERVINE, PSEUDOJERVINE, VERATROIDINE & VERATRALBINE. SIGNS OF POISONING WITH VERATRINE & RELATED ALKALOIDS ARE SALIVATION, PURGATION, VOMITING (EVEN IN THE COW), DIURESIS, EXCITABILITY FOLLOWED BY PROSTRATION, WEAK & IRREGULAR PULSE, DEEP & SLOW RESPIRATIONS, & DEATH IN CONVULSIONS OR CONSEQUENT UPON PARALYSIS. /VERATRINE & RELATED ALKALOIDS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

金仓鼠胎儿对颠茄碱的致畸作用极为敏感。在妊娠第7天给药时，会产生象鼻、兔唇/腭裂、脑外露和颅部水疱。源自斯普拉格-道莱的白色大鼠对颠茄碱不敏感；瑞士韦伯斯特小鼠也具有抵抗力。/颠茄碱/

GOLDEN HAMSTER FETUSES WERE EXTREMELY SENSITIVE TO THE TERATOGENIC ACTION OF JERVINE. CEBOCEPHALY, HARELIP/CLEFT PALATE, EXENCEPHALY AND A CRANIAL BLEB WERE PRODUCED BY DOSING ON THE 7TH DAY OF GESTATION. SPRAGUE-DAWLEY DERIVED ALBINO RATS WERE NOT SUSCEPTIBLE TO JERVINE; SWISS WEBSTER MICE WERE RESISTANT TOO. /JERVINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

1-2毫克茉莉酸应用于孵化14-18小时的小鸡窗化鸡蛋，产生了30-60%的头部畸形：独眼畸形、无眼畸形、小眼畸形、脑积水、脑膜膨出和脑膨出。在30-40小时以相似剂量处理，产生了30-56%的躯干和四肢畸形：无肢畸形、半肢畸形、脊柱前凸和脊柱裂。在绵羊中，于12、16和20天经子宫内注射1-2毫克，产生了半肢畸形、躯干部分无发育和整个胚胎的严重畸形。/茉莉酸/

1-2 mg jervine applied to windowed chick eggs at 14-18 hr incubation produced 30-60% head abnormalities: cyclopia, cebocephaly, microphthalmia, hydrocephalus, meningocele, and encephalocele. Similar doses at 30-40 hr produced 30-56% trunk and limb abnormalities: amelia, hemimelia, lordosis, and rachischisis. In sheep, intrauterine injection of 1-2 mg at 12, 16, and 20 days produced hemimelia, agenesia of portions of the trunk and gross abnormalities of the entire embryo. /Jervine/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

环肽是一种存在于加州藜芦根及根茎中的甾体生物碱，也被认为是一种致畸化合物。

反应信息

• 作为反应物：
  描述：

  11-去氧代介藜芦碱 beta-D-葡糖苷 在 水 、 三羟甲基氨基甲烷 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 22.0h， 生成 环巴胺
  参考文献：
  名称：

  Isolation of Cyclopamine

  摘要：

  提供了去糖化方法，旨在优化从鸢尾科植物材料和/或从鸢尾科植物材料提取物中提取鸢尾科生物碱的产量。

  公开号：

  US20160168193A1

文献信息

• Isolation of Cyclopamine
  申请人：Infinity Pharmaceuticals, Inc.

  公开号：US20160168193A1

  公开（公告）日：2016-06-16

  Provided are deglycosylation methods designed to optimize the yield of a Veratrum alkaloid from Veratrum plant material and/or from an extract of Veratrum plant material.

  提供了去糖化方法，旨在优化从鸢尾科植物材料和/或从鸢尾科植物材料提取物中提取鸢尾科生物碱的产量。