DL-甲状腺肿素 | 500-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: DL-甲状腺肿素
• 中文别名: 致甲状腺肿素
• 英文名称: goitrin
• 英文别名: (S)-5-Vinyloxazolidine-2-thione；(5S)-5-ethenyl-1,3-oxazolidine-2-thione
• CAS: 500-12-9
• 化学式: C₅H₇NOS
• 分子量: 129.183
• InChiKey: UZQVYLOFLQICCT-BYPYZUCNSA-N

物化性质

• 熔点：
  50°
• 比旋光度：
  D31 -70.5° (c = 2 in methanol)
• 颜色/状态：
  Large prisms from ether
• 稳定性/保质期：

  Stable in alkali, but not in acid.

• 旋光度：
  Specific optical rotation at 31 °C for D (sodium) line = -70.5 deg (c=2 in methanol).
• 解离常数：
  pKa = 10.5

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

毒理性

• 相互作用

Goitrin是一种强效致甲状腺肿物，已被证明能够诱导谷胱甘肽S-转移酶（GST）活性并增加黄曲霉毒素解毒。

Goitrin is a potent goitrogen that has been shown to induce glutathione S-transferase (GST) activity and to increase aflatoxin detoxification.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

亚硝基化甘蓝素是一种天然存在于十字花科蔬菜和油菜中的化合物，可以通过在胃部条件下用亚硝酸盐处理轻易地发生亚硝化反应，生成失去硫的N-亚硝基恶唑烷酮4。这个产物在Ames沙门氏菌/哺乳动物微粒体测试中的致突变模式和能力与N-亚硝基-N-甲基-N'-硝基胍（MNNG）相似。

goitrin --a naturally occurring compound in cruciferous vegetables and rape--could be easily nitrosated by treatment with nitrite under stomach conditions, yielding with loss of sulfur the N-nitroso- oxazolidone 4. This product has a mutagenicity pattern and potency similar to that of N-nitroso-N-methyl-N'- nitroguanidine (MNNG) in the Ames Salmonella/mammalian microsome test.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，并在需要时辅助通气。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，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预见并治疗癫痫发作……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干性无菌敷料覆盖皮肤烧伤……。/毒药A和B/

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽插管以控制气道。使用带有气囊面罩的装置进行正压通气技术可能有益。监测心率和必要时治疗心律失常。开始静脉输液，使用5%葡萄糖盐水/生理盐水维持静脉通路开放，最小流量保持。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量症状的低血压，谨慎给予液体。注意液体过载的迹象。使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/通过平行线分析评估了口服给予甘露素对雏鸡的拮抗甲状腺活性，使用了四个指标。甘露素在鸡体内的相对效力估计大约为PTU导致甲状腺肿大的0.31倍，对血浆甲状腺激素抑制效应的0.06倍，以及对腺体中甲状腺激素生物合成抑制效应的0.08倍。可以得出结论，当口服给予甘露素时，鸡的甲状腺激素合成并没有像甲状腺肿大所预期的那样受到明显抑制。

/LABORATORY ANIMALS: Acute Exposure/ Antithyroid activity of orally administered goitrin was assessed by parallel-line assay in chicks using four indices. The relative potency of goitrin in chicks was estimated to be approximately 0.31 times the potency of PTU in causing enlargement of thyroid gland, 0.06 times in effect on depression in plasma thyroid hormone, and 0.08 times in inhibitory effects on biosynthesis of thyroid hormone in the gland. It might be concluded that thyroid hormone synthesis is not so much suppressed to the degree expected from the enlargement of thyroid gland when goitrin is administered orally to the chick.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一共有六头牛，分成3组，在7天内喂食了含有6克/千克硫代葡萄糖苷的菜籽饼，不同数量。这些牛每天挤奶两次...当菜籽饼以总饲料的0.39%，1.9%和3.9%的比例喂食时，分别导致牛奶中硫代葡萄糖苷的平均值为37，163和707微克/升。这些值相当于饲料中原始前硫代葡萄糖苷含量的约0.1%的转移。最后一次喂食菜籽饼后12小时，牛奶中的硫代葡萄糖苷含量低于7ppb的检测限。

A total of six cows, divided into 3 groups, were fed various amounts of rape cake containing 6 g of goitrin/kg over a period of 7 days. The cows were milked twice a day ... . When rape cake was fed at 0.39, 1.9 and 3.9% resp. of the total feed this resulted in medium goitrin values of 37, 163 and 707 ug/l milk. These values correspond to a transfer of about 0.1% of the original progoitrin content in the feed. 12 h after the last rape feeding the amount of goitrin in the milk was below the detection limit of 7 ppb.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  DL-甲状腺肿素 在 sodium hydride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 18.0h， 生成 (2S)-2-vinyl-2,3-dihydro-5H-[1,3]oxazolo[2,3-b]quinazolin-5-one
  参考文献：
  名称：

  A new and rapid access to homochiral 2,3-dihydro-oxazolo[2,3-b]quinazolin-5-ones

  摘要：

  Starting from homochiral 1,3-oxazolidine-2-thiones 1, a two-step sequence led to homotopic 2,3-dihydro-oxazolo[2,3-b]quinazolin-5-one derivatives 3. The sequence was developed and studied regarding its scope and limitations. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00032-5
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 生成 DL-甲状腺肿素
  参考文献：
  名称：

  Senfölglukoside als genuine Muttersubstanzen von natürlich vorkommenden antithyreoiden Stoffen. XIII. Mitteilung über Senfölglukoside

  摘要：

  DOI：

  10.1002/ardp.19562890912

文献信息

• Preparation of (5R)-5-vinyloxazolidme-2-thione from natural epiprogoitrin using immobilized myrosinase
  作者：Onofrio Leoni、Christophe Marot、Patrick Rollin、Sandro Palmieri

  DOI：10.1016/0957-4166(94)80145-2

  日期：1994.7

  Starting from (2S)-2-hydroxybut-3-enyl glucosinolate, i.e. epi-progoitrin 3, isolated from Crambe abyssinica ripe seeds, (5R)-5-vinyloxazolidine-2-thione (VOT) 8 was produced in enantiomerically pure form and high yield using a small bioreactor containing myrosinase-purified from Sinapis alba - immobilized on 18–36 mesh granular Nylon 6.6.

  从（2S）-2-羟基丁-3-烯基芥子油苷，即Epi-progoitrin 3（从Crambe abyssinica成熟种子中分离）开始，以对映体纯净形式生产（5R）-5-乙烯基恶唑烷-2-硫酮（VOT）8，使用小型生物反应器可实现高产量，该生物反应器含有从芥末（Sinapis alba）纯化的黑芥子酶-固定在18-36目粒状尼龙6.6上。
• The Arabidopsis Epithiospecifier Protein Promotes the Hydrolysis of Glucosinolates to Nitriles and Influences <i>Trichoplusia ni</i> Herbivory
  作者：Virginia Lambrix、Michael Reichelt、Thomas Mitchell-Olds、Daniel J. Kliebenstein、Jonathan Gershenzon

  DOI：10.1105/tpc.010261

  日期：2001.12

  Glucosinolates are anionic thioglucosides that have become one of the most frequently studied groups of defensive metabolites in plants. When tissue damage occurs, the thioglucoside linkage is hydrolyzed by enzymes known as myrosinases, resulting in the formation of a variety of products that are active against herbivores and pathogens. In an effort to learn more about the molecular genetic and biochemical regulation of glucosinolate hydrolysis product formation, we analyzed leaf samples of 122 Arabidopsis ecotypes. A distinct polymorphism was observed with all ecotypes producing primarily isothiocyanates or primarily nitriles. The ecotypes Columbia (Col) and Landsberg erecta (Ler) differed in their hydrolysis products; therefore, the Col × Ler recombinant inbred lines were used for mapping the genes controlling this polymorphism. The major quantitative trait locus (QTL) affecting nitrile versus isothiocyanate formation was found very close to a gene encoding a homolog of a Brassica napus epithiospecifier protein (ESP), which causes the formation of epithionitriles instead of isothiocyanates during glucosinolate hydrolysis in the seeds of certain Brassicaceae. The heterologously expressed Arabidopsis ESP was able to convert glucosinolates both to epithionitriles and to simple nitriles in the presence of myrosinase, and thus it was more versatile than previously described ESPs. The role of ESP in plant defense is uncertain, because the generalist herbivore Trichoplusia ni (the cabbage looper) was found to feed more readily on nitrile-producing than on isothiocyanate-producing Arabidopsis. However, isothiocyanates are frequently used as recognition cues by specialist herbivores, and so the formation of nitriles instead of isothiocyanates may allow Arabidopsis to be less apparent to specialists.

  硫代葡萄糖苷是阴离子硫代葡萄糖苷，已成为植物防御代谢物中最常被研究的类别之一。当组织受损时，硫代葡萄糖苷键会被一种名为芥子酶的酶水解，从而形成多种对食草动物和病原体具有活性的产物。为了进一步了解硫代葡萄糖苷水解产物形成的分子遗传和生化调控，我们对122种拟南芥生态型的叶片样本进行了分析。我们发现，所有生态型都表现出明显的多态性，它们主要产生异硫氰酸酯或腈。哥伦比亚（Col）和兰茨贝格直立（Ler）生态型的水解产物不同，因此，我们使用Col×Ler重组自交系来绘制控制这种多态性的基因。我们发现，影响腈和异硫氰酸酯形成的主要数量性状位点（QTL）非常接近编码油菜素内酯类同源蛋白（ESP）的基因，在某些十字花科植物的种子中，该蛋白在硫代葡萄糖苷水解过程中会导致形成表硫腈而不是异硫氰酸酯。异源表达的拟南芥ESP能够在芥子酶的作用下将硫代葡萄糖苷转化为表硫腈和简单腈，因此它比之前描述的ESP更具通用性。
• Kjaer et al., Acta Chemica Scandinavica (1947), 1959, vol. 13, p. 144,148,149
  作者：Kjaer et al.

  DOI：——

  日期：——
• Chemo-enzymatic preparation from renewable resources of enantiopure 1,3-oxazolidine-2-thiones
  作者：Onofrio Leoni、Roberta Bernardi、David Gueyrard、Patrick Rollin、Sandro Palmieri

  DOI：10.1016/s0957-4166(99)00574-1

  日期：1999.12

  Chiral 1,3-oxazolidine-2-thiones were prepared in enantiopure form from renewable resources through an enzymatic process involving immobilized myrosinase (thioglucoside glucohydrolase E.C. 3.2.3.1). (C) 2000 Elsevier Science Ltd. AII rights reserved.
• Antiviral activity of Isatidis Radix derived glucosinolate isomers and their breakdown products against influenza A in vitro/ovo and mechanism of action
  作者：Li-xing Nie、Yan-lin Wu、Zhong Dai、Shuang-cheng Ma

  DOI：10.1016/j.jep.2020.112550

  日期：2020.4

  Ethnopharmacological relevance: Isatidis Radix, the sun-dried roots of Isatis indigotica Fortune ex Lindl., is one of the most usually used traditional Chinese medicines. For centuries, the herb has been employed in clinical practice for treatment of virus infection and inflammation. However, its active ingredients remain unclear.Aim of the study: In the present study, the anti-influenza virus activity of epiprogoitrin, progoitrin, epigoitrin and goitrin, the Isatidis Radix derived glucosinolate isomers and their breakdown products, was firstly evaluated in vitro and in ovo and their mechanism of action was investigated.Materials and methods: Epiprogoitrin, progoitrin, epigoitrin and goitrin were isolated from Isatidis Radix by chiral separation. In vitro and in ovo evaluations were performed on Madin-Darby canine kidney (MDCK) cells and embryonated eggs respectively, both using protocols including prevention, treatment and virus neutralization. Hemagglutination (HA) and neuraminidase (NA) inhibition assays were performed for further understanding of the antiviral mechanism.Results: Isatidis Radix derived glucosinolate isomers and their breakdown products all exhibited dose-dependent inhibition effect against influenza A virus (H1N1) without toxicity. The antiviral potency of the components was in the order of progoitrin > goitrin > epigoitrin > epiprogoitrin. The attachment of the constituents to the viral envelope conduced to the mechanism of their antiviral action without disturbing viral adsorption or budding.Conclusion: Taken together, these results are promising for further development of Isatidis Radix and may contribute an adjunct to pharmacotherapy for influenza virus infection.