ochratoxin A

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 赭曲霉毒素及相关物质
• 英文名称: ochratoxin A
• 英文别名: N-[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-2-benzopyran-7-carbonyl]-D-phenylalanine；(2R)-2-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoic acid
• 化学式: C₂₀H₁₈ClNO₆
• 分子量: 403.819
• InChiKey: RWQKHEORZBHNRI-MEBBXXQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ochratoxin A 在 盐酸 、 水 作用下， 反应 24.0h， 生成 D-苯丙氨酸 、 5-氯-8-羟基-3-甲基-1-氧代异色满-7-羧酸
  参考文献：
  名称：

  Identification and in Vitro Cytotoxicity of Ochratoxin A Degradation Products Formed during Coffee Roasting

  摘要：

  The mycotoxin ochratoxin A is degraded by up to 90% during coffee roasting. In order to investigate this degradation, model heating experiments with ochratoxin A were carried out, and the reaction products were analyzed by HPI-C-DAID and HPLC-MS/MS. Two ochratoxin A degradation products were identified, and their structure and absolute configuration were determined. As degradation reactions, the isomerization to 14-(R)-ochratoxin A and the decarboxylation to 14-decarboxy-ochratoxin A were identified. Subsequently, an analytical method for the determination of these compounds in roasted coffee was developed. Quantification was carried out by HPLC-MS/MS and the use of stable isotope dilution analysis. By using this method for the analysis of 15 coffee samples from the German market, it could be shown that, during coffee roasting, the ochratoxin A diastereomer 14-(R)-ochratoxin A was formed in amounts of up to 25.6% relative to ochratoxin A. The decarboxylation product was formed only in traces. For toxicity evaluations, first preliminary cell culture assays were performed with the two new substances. Both degradation products exhibited higher IC50 values and caused apoptotic effects with higher concentrations than ochratoxin A in cultured human kidney epithelial cells. Thus, these cell culture data suggest that the degradation products are less cytotoxic than ochratoxin A.

  DOI：

  10.1021/jf801296z
• 作为产物：
  描述：

  赭曲霉毒素A 反应 0.17h， 以42%的产率得到ochratoxin A
  参考文献：
  名称：

  Identification and in Vitro Cytotoxicity of Ochratoxin A Degradation Products Formed during Coffee Roasting

  摘要：

  The mycotoxin ochratoxin A is degraded by up to 90% during coffee roasting. In order to investigate this degradation, model heating experiments with ochratoxin A were carried out, and the reaction products were analyzed by HPI-C-DAID and HPLC-MS/MS. Two ochratoxin A degradation products were identified, and their structure and absolute configuration were determined. As degradation reactions, the isomerization to 14-(R)-ochratoxin A and the decarboxylation to 14-decarboxy-ochratoxin A were identified. Subsequently, an analytical method for the determination of these compounds in roasted coffee was developed. Quantification was carried out by HPLC-MS/MS and the use of stable isotope dilution analysis. By using this method for the analysis of 15 coffee samples from the German market, it could be shown that, during coffee roasting, the ochratoxin A diastereomer 14-(R)-ochratoxin A was formed in amounts of up to 25.6% relative to ochratoxin A. The decarboxylation product was formed only in traces. For toxicity evaluations, first preliminary cell culture assays were performed with the two new substances. Both degradation products exhibited higher IC50 values and caused apoptotic effects with higher concentrations than ochratoxin A in cultured human kidney epithelial cells. Thus, these cell culture data suggest that the degradation products are less cytotoxic than ochratoxin A.

  DOI：

  10.1021/jf801296z

文献信息

• Total synthesis and cytotoxicity evaluation of all ochratoxin A stereoisomers
  作者：Benedikt Cramer、Henning Harrer、Kazuhiko Nakamura、Daisuke Uemura、Hans-Ulrich Humpf

  DOI：10.1016/j.bmc.2009.10.050

  日期：2010.1

  The mycotoxin ochratoxin A is a potent inhibitor of the protein biosynthesis and known to be cytotoxic in nanomolar concentrations. In order to investigate the relationship between stereochemistry and cytotoxicity of this compound, all four ochratoxin A stereoisomers have been synthesized. Using the liver cell line Hep G2, the compounds were tested for cytotoxic and apoptotic potential. It could be shown, that the L-configuration of the phenylalanine moiety of the molecule is mostly responsible for the high cytotoxicity of ochratoxin A while the stereocenter at the dihydroisocoumarine structure is of less importance. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and structural elucidation of analogs of ochratoxin A
  作者：Hao Xiao、Ronald R. Marquardt、Andrew A. Frohlich、Yang Z. Ling

  DOI：10.1021/jf00050a050

  日期：1995.2

  Five analogs of ochratoxin A (OA) including the ethylamide of OA (OE-OA), the D-phenylalanine form of OA (d-OA), the decarboxylated OA (DC-OA), the O-methyl ether of OA (OM-OA), and the methyl ester of ochratoxin alpha (M-O alpha) were synthesized using OA or ochratoxin alpha (O alpha) as the starting material. The reactions involved activation of OA to the N-hydroxysuccinimide ester (OA-NHS) and of O alpha to acyl chloride (O alpha-Cl) followed by nucleophilic substitution with primary amines, amino acids, and alcohols to form corresponding amides and esters. All analogs were obtained in pure forms, and all but OM-OA were crystallized. A simplified procedure for the isolation and crystallization of O alpha was also developed. The chemical structures of all analogs were elucidated using EI-MS and H-1 NMR. Other physicochemical parameters such as melting point, UV-vis absorption, fluorescence, and HPLC elution pattern for each analog are presented. The procedures that have been developed for the synthesis of the analogs of OA from OA or O alpha are simple and efficient. The reactions generally result in high yields of the desired compounds. The overall yields of final products range approximately from 85 to 90% of the starting materials. The analogs synthesized together with the natural analogs of OA can be used to establish the structure-activity relationship of OA and for metabolic and immunological studies.
• Identification and in Vitro Cytotoxicity of Ochratoxin A Degradation Products Formed during Coffee Roasting
  作者：Benedikt Cramer、Maika Königs、Hans-Ulrich Humpf

  DOI：10.1021/jf801296z

  日期：2008.7.1

  The mycotoxin ochratoxin A is degraded by up to 90% during coffee roasting. In order to investigate this degradation, model heating experiments with ochratoxin A were carried out, and the reaction products were analyzed by HPI-C-DAID and HPLC-MS/MS. Two ochratoxin A degradation products were identified, and their structure and absolute configuration were determined. As degradation reactions, the isomerization to 14-(R)-ochratoxin A and the decarboxylation to 14-decarboxy-ochratoxin A were identified. Subsequently, an analytical method for the determination of these compounds in roasted coffee was developed. Quantification was carried out by HPLC-MS/MS and the use of stable isotope dilution analysis. By using this method for the analysis of 15 coffee samples from the German market, it could be shown that, during coffee roasting, the ochratoxin A diastereomer 14-(R)-ochratoxin A was formed in amounts of up to 25.6% relative to ochratoxin A. The decarboxylation product was formed only in traces. For toxicity evaluations, first preliminary cell culture assays were performed with the two new substances. Both degradation products exhibited higher IC50 values and caused apoptotic effects with higher concentrations than ochratoxin A in cultured human kidney epithelial cells. Thus, these cell culture data suggest that the degradation products are less cytotoxic than ochratoxin A.