(+)-S-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine | 26400-24-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯嗪
• 英文名称: (+)-S-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine
• 英文别名: (+)-dehydroheliotridine；dehydroheliotridine；Dehydroheliotridin；(1S)-7-(hydroxymethyl)-2,3-dihydro-1H-pyrrolizin-1-ol
• CAS: 26400-24-8
• 化学式: C₈H₁₁NO₂
• 分子量: 153.181
• InChiKey: QFPRRXUPCPFWKD-ZETCQYMHSA-N

物化性质

• 沸点：
  276.1°C (rough estimate)
• 密度：
  1.1577 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.4
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

LASIOCARPINE 和 HELIOTRINE 在大鼠肝微粒体体外代谢中转化为一种主要的水溶性氯仿提取物吡咯衍生物，该衍生物通过色谱、核磁共振和质谱鉴定为去氢海里奥特里定 6,7-二氢-7A-羟基-1-羟甲基-5H-吡咯里嗪。

LASIOCARPINE AND HELIOTRINE WERE METABOLIZED IN VITRO BY RAT LIVER MICROSOMES TO ONE MAJOR CHLOROFORM-EXTRACTABLE AND WATER-SOLUBLE PYRROLE DERIVATIVE WHICH WAS ISOLATED AND IDENTIFIED BY CHROMATOGRAPHY, NUCLEAR MAGNETIC RESONANCE, AND MASS SPECTROSCOPY AS DEHYDROHELIOTRIDINE 6,7-DIHYDRO-7A-HYDROXY-1-HYDROXYMETHYL-5H-PYRROLIZINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

去氢海罂粟碱是毛茛碱和海罂粟碱（均来自海罂粟，海罂粟是导致澳大利亚羊因摄入吡咯里西啶生物碱而死亡的最常见植物）的主要未结合、相对稳定的代谢物。

DEHYDROHELIOTRIDINE IS THE MAJOR UNBOUND, RELATIVELY STABLE METABOLITE OF LASIOCARPINE AND HELIOTRINE (BOTH FROM HELIOTROPIUM EUROPAEUM, THE MOST COMMON PLANT INVOLVED IN DEATH OF AUSTRALIAN SHEEP DUE TO INGESTION OF PYRROLIZIDINE ALKALOIDS).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当通过腹腔注射将去氢海洛托品给予一种带有帽状突起的鼠类品种时，去氢海洛托品显著缩短了鼠类的寿命，而去氢海洛托品和硫乙酰胺联合治疗则缩短得更多，但单独使用硫乙酰胺并未缩短寿命。

WHEN DEHYDROHELIOTRIDINE WAS ADMINISTERED TO A HOODED STRAIN OF RATS BY IP INJECTION, THE LIFE-SPAN OF THE RATS WAS SIGNIFICANTLY SHORTENED BY DEHYDROHELIOTRIDINE AND MORE SO BY COMBINED DEHYDROHELIOTRIDINE AND THIOACETAMIDE TREATMENT, BUT NOT BY THIOACETAMIDE ALONE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

脱氢heliotrine在培养的山羊肾细胞中，选择性地抑制了卫星DNA的半保留复制。对卫星DNA合成的抑制可能与代谢物对着丝粒区域的攻击有关，大多数卫星序列都位于这个区域。

DEHYDROHELIOTRIDINE SELECTIVELY INHIBITED THE SEMICONSERVATIVE REPLICATION OF THE SATELLITE DNA IN CULTURES OF OVINE KIDNEY CELLS. THE INHIBITION OF THE SYNTHESIS OF SATELLITE DNA MAY BE RELATED TO AN ATTACK BY THE METABOLITE ON THE PERICENTROMERIC REGION WHERE THE MAJORITY OF THE SATELLITE SEQUENCES ARE LOCATED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在怀孕的第14天，给雌性带帽大鼠腹腔注射去氢海罂粟碱（DHH），剂量为30-90毫克/千克，并在第20天评估胚胎效应。DHH既具有生长抑制作用也具有致畸作用。主要异常包括骨骼方面的，如骨骼形成迟缓、肋骨和长骨扭曲、腭裂和足部缺陷。在更高剂量下，许多组织的生长几乎停止，尽管超过60%的胚胎仍然存活，但它们无法在出生时存活。所有胚胎都非常不成熟，并且具有多种骨骼和内脏缺陷。在肝脏观察到的影响异常，因为胚胎实质对DHH的抗有丝分裂活性几乎没有反应。

FEMALE HOODED RATS WERE INJECTED IP ON THE 14TH DAY OF PREGNANCY WITH DEHYDROHELIOTRIDINE (DHH) AT 30-90 MG/KG AND THE EMBRYONAL EFFECTS EVALUATED ON THE 20TH DAY. DHH WAS BOTH GROWTH-RETARDING AND TERATOGENIC. PRINCIPAL ABNORMALITIES WERE SKELETAL, INCLUDING RETARDED OSSIFICATION, DISTORTED RIBS AND LONG BONES, CLEFT PALATE, AND FEET DEFECTS. AT HIGHER DOSE RATES, GROWTH ALMOST CEASED IN MANY TISSUES AND ALTHOUGH GREATER THAN 60% OF THE EMBRYOS WERE STILL ALIVE, THEY WOULD NOT HAVE SURVIVED BIRTH. ALL WERE VERY IMMATURE AND HAD MULTIPLE SKELETAL AND VISCERAL DEFECTS. THE EFFECTS OBSERVED IN THE LIVER WERE ANOMALOUS IN THAT THE EMBRYONIC PARENCHYMA SHOWED LITTLE RESPONSE TO THE ANTIMITOTIC ACTIVITY OF DHH.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

当通过腹腔注射的方式向一种带有帽兜的鼠类品种给予脱氢黑麦碱时，除间质细胞瘤外，肿瘤的发生率显著高于注射生理盐水的对照组。脱氢黑麦碱显著缩短了这些大鼠的寿命。

WHEN DEHYDROHELIOTRIDINE WAS ADMINISTERED TO A HOODED STRAIN OF RATS BY IP INJECTION, THE INCIDENCE OF TUMORS, EXCLUDING INTERSTITIAL CELL TUMORS, WAS SIGNIFICANTLY GREATER THAN THAT IN SALINE-INJECTED CONTROLS. THE LIFE-SPAN OF THE RATS WAS SIGNIFICANTLY SHORTENED BY DEHYDROHELIOTRIDINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

脱氢海罂粟碱降低了小鼠对绵羊红细胞和流感病毒疫苗的初次免疫反应。只有当脱氢海罂粟碱在二次刺激时给予时，对绵羊红细胞的二次免疫反应才会被抑制。

DEHYDROHELIOTRIDINE DECREASED THE PRIMARY RESPONSE TO SHEEP RED BLOOD CELLS AND TO INFLUENZA VIRUS VACCINE IN MICE. THE SECONDARY RESPONSE TO SHEEP RED BLOOD CELLS WAS SUPPRESSED ONLY IF DEHYDROHELIOTRIDINE WAS GIVEN AT THE TIME OF THE SECONDARY STIMULUS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  1-aza-4-(1,3-dithian-2-ylidene)-6(S)-(acetyloxy)bicyclo<3.3.0>octan-8-one 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 calcium carbonate 、 mercury dichloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 2.33h， 生成 (+)-S-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine
  参考文献：
  名称：

  Enantioselective synthesis of seven pyrrolizidine diols from a single precursor

  摘要：

  DOI：

  10.1021/jo00223a002

文献信息

• Enantioselective synthesis of seven pyrrolizidine diols from a single precursor
  作者：A. Richard Chamberlin、John Y. L. Chung

  DOI：10.1021/jo00223a002

  日期：1985.11