3-(S-allyl-S-dioxomercapto)-1,2-epoxypropane | 7566-04-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 磺酰类
• 英文名称: 3-(S-allyl-S-dioxomercapto)-1,2-epoxypropane
• 英文别名: 2-(Prop-2-enylsulfonylmethyl)oxirane
• CAS: 7566-04-3
• 化学式: C₆H₁₀O₃S
• 分子量: 162.21
• InChiKey: NCFHQPRGNQUELC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 3-(S-allyl-S-dioxomercapto)-1,2-epoxypropane 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以30%的产率得到S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]glutathione
  参考文献：
  名称：

  Metabolism of the Chemoprotective Agent Diallyl Sulfide to Glutathione Conjugates in Rats

  摘要：

  The chemoprotective effects of diallyl sulfide (DAS), a flavor component of garlic, have been attributed to its inhibitory effects on CYP2E1-mediated bioactivation of certain carcinogenic chemicals. In addition to being a competitive inhibitor of CYP2E1 in vitro, DAS is known to cause irreversible inhibition of CYP2E1 in rats in vivo. The latter property is believed to be mediated by the DAS metabolite diallyl sulfone (DASO(2)), which is thought to be a mechanism-based inhibitor of CYP2E1, although the underlying mechanism remains unknown. In order to investigate the nature of the reactive intermediate(s) responsible for the inactivation of CY2BE1 by DAS and its immediate metabolites, the present studies were carried out to detect and identify potential glutathione (GSH) conjugates of DAS and its metabolites diallyl sulfoxide (DASO) and DASO(2). By means of ionspray LC-MS/MS, ten GSH conjugates were identified in bile collected from rats dosed with DAS, namely: S-[3-(S'-allyl-S'-oxomercapto)-2-hydroxypropyl]glutathione (M1, M2; diastereomers), S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]-glutathione (M5), S-[2-(S'-allyl-S'-dioxomercapto)-1-(hydroxymethyl)ethyl]glutathione (M3, M4; diastereomers), S-[3-(S'-allylmercapto)-2-hydroxypropyl]glutathione(M6), S-(3-hydroxypropyl)-glutathione (M7), S-(2-carboxyethyl)glutathione (M8), allyl glutathionyl disulfide (M9), and S-allylglutathione (M10). With the exception of M6, all of the above GSH conjugates were detected in the bile of rats treated with DASO, while only M3, M4, M5, M8, and M10 were found in the bile of rats treated with DASO(2). Experiments conducted in vitro showed that GSH reacted spontaneously with DASO to form conjugates M9 and M10, and with DASO(2) to form M10. In the presence of NADPH and GSH, incubation of DAS with cDNA-expressed rat CYP2E1 resulted in the formation of metabolites M6, M9, and M10, while incubation with DASO led to the formation of M3, M4, M5, M9, and M10. When DASO(2) acted as substrate, CY2BE1 generated only conjugates M3, M4, M5, and M10. These results indicate that while DAS and DASO undergo extensive oxidation in vice at the sulfur atom, the allylic carbon, and the terminal double bonds, CY2BE1 preferentially catalyzes oxidation of the sulfur atom to form the sulfoxide and the sulfone (DASO and DASO(2)). However, it appears that the end product of this sequence, namely, DASO(2), undergoes further CYP2E1-mediated activation of the olefinic pi-bond, a reaction which transforms many terminal olefins to potent mechanism-based P450 inhibitors. We hypothesize, therefore, that it is this final metabolic event with DASO(2) which leads to autocatalytic destruction of CYP2E1 and which is mainly responsible for the chemoprotective effects of DAS in vivo.

  DOI：

  10.1021/tx9601768
• 作为产物：
  描述：

  二烯丙基砜 在 p-nitroperoxybenzoic acid 作用下， 以 氯仿 为溶剂， 反应 10.0h， 以21%的产率得到3-(S-allyl-S-dioxomercapto)-1,2-epoxypropane
  参考文献：
  名称：

  Metabolism of the Chemoprotective Agent Diallyl Sulfide to Glutathione Conjugates in Rats

  摘要：

  The chemoprotective effects of diallyl sulfide (DAS), a flavor component of garlic, have been attributed to its inhibitory effects on CYP2E1-mediated bioactivation of certain carcinogenic chemicals. In addition to being a competitive inhibitor of CYP2E1 in vitro, DAS is known to cause irreversible inhibition of CYP2E1 in rats in vivo. The latter property is believed to be mediated by the DAS metabolite diallyl sulfone (DASO(2)), which is thought to be a mechanism-based inhibitor of CYP2E1, although the underlying mechanism remains unknown. In order to investigate the nature of the reactive intermediate(s) responsible for the inactivation of CY2BE1 by DAS and its immediate metabolites, the present studies were carried out to detect and identify potential glutathione (GSH) conjugates of DAS and its metabolites diallyl sulfoxide (DASO) and DASO(2). By means of ionspray LC-MS/MS, ten GSH conjugates were identified in bile collected from rats dosed with DAS, namely: S-[3-(S'-allyl-S'-oxomercapto)-2-hydroxypropyl]glutathione (M1, M2; diastereomers), S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]-glutathione (M5), S-[2-(S'-allyl-S'-dioxomercapto)-1-(hydroxymethyl)ethyl]glutathione (M3, M4; diastereomers), S-[3-(S'-allylmercapto)-2-hydroxypropyl]glutathione(M6), S-(3-hydroxypropyl)-glutathione (M7), S-(2-carboxyethyl)glutathione (M8), allyl glutathionyl disulfide (M9), and S-allylglutathione (M10). With the exception of M6, all of the above GSH conjugates were detected in the bile of rats treated with DASO, while only M3, M4, M5, M8, and M10 were found in the bile of rats treated with DASO(2). Experiments conducted in vitro showed that GSH reacted spontaneously with DASO to form conjugates M9 and M10, and with DASO(2) to form M10. In the presence of NADPH and GSH, incubation of DAS with cDNA-expressed rat CYP2E1 resulted in the formation of metabolites M6, M9, and M10, while incubation with DASO led to the formation of M3, M4, M5, M9, and M10. When DASO(2) acted as substrate, CY2BE1 generated only conjugates M3, M4, M5, and M10. These results indicate that while DAS and DASO undergo extensive oxidation in vice at the sulfur atom, the allylic carbon, and the terminal double bonds, CY2BE1 preferentially catalyzes oxidation of the sulfur atom to form the sulfoxide and the sulfone (DASO and DASO(2)). However, it appears that the end product of this sequence, namely, DASO(2), undergoes further CYP2E1-mediated activation of the olefinic pi-bond, a reaction which transforms many terminal olefins to potent mechanism-based P450 inhibitors. We hypothesize, therefore, that it is this final metabolic event with DASO(2) which leads to autocatalytic destruction of CYP2E1 and which is mainly responsible for the chemoprotective effects of DAS in vivo.

  DOI：

  10.1021/tx9601768

文献信息

• Premdas, Peter D.; Bowers, Raymond J.; Forkert, Poh-Gek, Journal of Pharmacology and Experimental Therapeutics, 2000, vol. 293, # 3, p. 1112 - 1120
  作者：Premdas, Peter D.、Bowers, Raymond J.、Forkert, Poh-Gek

  DOI：——

  日期：——
• US4246332A
  申请人：——

  公开号：US4246332A

  公开（公告）日：1981-01-20