S-(2-carboxyethyl)glutathione

• 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
• 英文名称: S-(2-carboxyethyl)glutathione
• 英文别名: L-Gamma-Glutamyl-S-(2-Carboxyethyl)-L-Cysteinylglycine；(2S)-2-amino-5-[[(2R)-3-(2-carboxyethylsulfanyl)-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₁₃H₂₁N₃O₈S
• 分子量: 379.391
• InChiKey: ILLXYSCGSHMUFK-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  221
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-溴丙酸 、 谷胱甘肽 在 氢氧化钾 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以65%的产率得到S-(2-carboxyethyl)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

文献信息

• Formation of a Vitamin C Conjugate of Acrolein and Its Paraoxonase-Mediated Conversion into 5,6,7,8-Tetrahydroxy-4-oxooctanal
  作者：Nicholas G. Kesinger、Brandi L. Langsdorf、Alexandre F. Yokochi、Cristobal L. Miranda、Jan F. Stevens

  DOI：10.1021/tx900452j

  日期：2010.4.19

  intermediate carboxylic acid. Subsequent decarboxylation of the carboxylic acid yielded 5,6,7,8-tetrahydroxy-4-oxooctanal (THO). When THP-1 cells were pretreated with ascorbic acid (1 mM, 18 h) and then exposed to acrolein diacetate, THO was detected as its pentafluorobenzyl oxime derivative in the cell lysates and medium. Treatment of THP-1 cells with both ascorbic acid and acrolein diacetate was required

  据报道，维生素 C（抗坏血酸）参与体外迈克尔加成反应，与 α,β-不饱和醛（如丙烯醛）形成维生素 C 缀合物。该研究显示了丙烯醛维生素 C 结合物 (AscACR) 在暴露于丙烯醛二乙酸酯的培养的人类单核细胞 THP-1 细胞中形成和代谢的证据。通过使用18 O 和13C 标记与液相色谱-串联质谱法相结合，显示 AscACR 将抗坏血酸内酯水解转化为中间体羧酸。随后羧酸的脱羧产生 5,6,7,8-四羟基-4-氧代辛醛 (THO)。当 THP-1 细胞用抗坏血酸 (1 mM, 18 h) 预处理，然后暴露于二乙酸丙烯醛时，在细胞裂解物和培养基中检测到 THO 作为其五氟苄基肟衍生物。THO形成需要用抗坏血酸和丙烯醛二乙酸酯处理THP-1细胞。内酯酶、人重组对氧磷酶 1 和 2 促进了 AscACR 形成 THO。THP-1 细胞表现出 PON 活性，这解释了 AscACR 在这些细胞中催化转化为
• HEPATIC DISORDER INHIBITOR
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP0480061A1

  公开（公告）日：1992-04-15

  A hepatic disorder inhibitor containing as the active ingredient an S-(lower aliphatic acid)-substituted glutathione derivative of general formula (I) or its salt, wherein R₁ and R₃ may be the same or different from each other and each represents hydrogen or optimally substituted lower alkyl; R₄ represents hydroxy, optimally substituted lower alkoxy or optimally substituted amino; n is 0 or 1; and when n is 1, R₂ represents hydrogen, optimally substituted lower alkyl or optimally substituted phenyl.

  一种肝功能紊乱抑制剂，含有通式(I)的 S-(低级脂肪族酸)-取代的谷胱甘肽衍生物或其盐作为活性成分，其中 R₁ 和 R₃ 可以相同或不同，各自代表氢或最佳取代的低级烷基；R₄ 代表羟基、最佳取代的低级烷氧基或最佳取代的氨基；n 为 0 或 1；当 n 为 1 时，R₂ 代表氢、最佳取代的低级烷基或最佳取代的苯基。
• US3984569A
  申请人：——

  公开号：US3984569A

  公开（公告）日：1976-10-05
• US5232913A
  申请人：——

  公开号：US5232913A

  公开（公告）日：1993-08-03
• [EN] METHODS FOR PREPARING ANTHRACYCLINONE DERIVATIVES AND ANTHRACYCLINONE DERIVATIVES PER SE<br/>[FR] METHODES PERMETTANT DE PREPARER DES DERIVES D'ANTHRACYCLINONE ET LESDITS DERIVES D'ANTHRACYCLINONE
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2003057896A1

  公开（公告）日：2003-07-17

  The present invention relates to a process for preparation of a product compound of the Formula (I), where R1 is an acyl group, R2 is H, an N-alkylated amino sugar, or a non-basic sugar moiety, and R3 is H, OH, or OCH3. The process involves reacting a starting compound of the Formula (II) with an acyl donor compound in the presence of a non-chemically modified lipase, under conditions effective to produce the product compound. Another aspect of the present invention relates to a compound of the following Formula (III), where: R1 is an acyl radical of a carboxylic acid selected from the group consisting of: polyethylene glycol acetic acid and polyunsaturated fatty acid; and R2 = 2,6-dideoxy-2-fluoro-α-talopyranosyl; 3-trifluoroacetylamino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl; or 3-deamino-3-(2'-pyrroline-1'-yl)-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl; or a pharmaceutically acceptable salt thereof. The present invention also relates to a compound of the Formula (IV) where n is 4 or 5, or a pharmaceutically acceptable salt thereof. Another aspect of the present invention relates to a compound of the Formula (V) where: R1 is an acyl group, R2 is 3-substituted allyloxycarbonylamino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl, R3 is H, OH, or OCH3.