(+)-N-([(3S)-5-chloro-8-hydroxy-3-methyl-1-oxoisochroman-7-yl]carbonyl)-L phenylalanine

• 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: (+)-N-([(3S)-5-chloro-8-hydroxy-3-methyl-1-oxoisochroman-7-yl]carbonyl)-L phenylalanine
• 英文别名: ochratoxin A；13S-ochratoxin A；(3S,14S)-ochratoxin A；N-(((3S)-5-chloro-3,4-dihydro-8-hydroxy-3-methyl-1-oxo-1H-2-benzopyran-7-yl)carbonyl)-L-phenylalanine；3-epi-Ochratoxin A；(2S)-2-[[(3S)-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-BONVTDFDSA-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

ADMET

代谢

3s14s-赭曲霉毒素A已知的人类代谢物包括2-[(5-氯-4,8-二羟基-3-甲基-1-氧代-3,4-二氢异色烯-7-甲酸基)氨基]-3-苯基丙酸。

3s14s-ochratoxin a has known human metabolites that include 2-[(5-Chloro-4,8-dihydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl)amino]-3-phenylpropanoic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  tert-butyl N-((5-chloro-8-hydroxy-3-methyl-1-oxoisochroman-7-yl)carbonyl)-L-phenylalaninate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以46%的产率得到赭曲霉毒素A
  参考文献：
  名称：

  ch曲霉毒素A和d5- ch曲霉毒素A的一种新型简便的全合成方法

  摘要：

  提出了一种新的真菌毒素曲霉毒素A（OTA）的全合成方法，该方法以市售底物的总收率为9％制备。关键步骤包括受保护的1-苯丙氨酸与5-氯-8-羟基-3-甲基-1-甲基-1-氧代异色烷-7-羧酸（och曲霉毒素α，OTα）之间的缩合反应。相同的策略可以成功地应用于l - d 5-苯丙氨酸，导致首次完全合成d 5 -OTA，这是一种分子示踪剂，用于通过稳定同位素稀释测定法检测和分析定量食品中的天然霉菌毒素（SIDA）。 杂环-天然产物-曲霉毒素A-稳定同位素稀释法-全合成

  DOI：

  10.1055/s-0028-1088076

文献信息

• Synthesis of analogues of ochratoxin A
  作者：Pierluigi Plastina、Alessia Fazio、Mohamed Attya、Giovanni Sindona、Bartolo Gabriele

  DOI：10.1080/14786419.2011.613385

  日期：2012.10

  Four analogues of ochratoxin A (OTA) differing for the aminoacidic moiety were synthesised using ochratoxin α (OTα) as the starting material. The condensation reaction between protected amino acids and OTα, carried out in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC • HCl) and N-hydroxybenzotriazole (HOBt) as coupling agents, followed by deprotection and PTLC purification

  赭曲霉毒素A（OTA）的四个不同的类似物为aminoacidic部分使用赭曲霉毒素合成α（OT α）作为起始材料。保护的氨基酸和OT之间的缩合反应α，在1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐（EDC•HCl）中和的存在下进行Ñ羟基苯并三唑（HOBt）作为偶联剂，接着脱保护和PTLC纯化得到OTA丙氨酸，亮氨酸，丝氨酸和在令人满意的产率色氨酸类似物（33-47％，基于OT α）。
• First Synthesis of a Stable Isotope of Ochratoxin A Metabolite for a Reliable Detoxification Monitoring
  作者：Anaïs Bouisseau、Aurélie Roland、Florence Reillon、Rémi Schneider、Florine Cavelier

  DOI：10.1021/ol401630t

  日期：2013.8.2

  Due to its toxicity and presence in numerous food products, Ochratoxin A (OTA) has drawn attention for decades. This article summarizes the first synthesis of a labeled analogue of Ochratoxin alpha (OT alpha), one of the main products generated by the metabolization of OTA by microorganisms. This synthesis also led to a new labeled analogue of OTA with the deuteration located on the dihydroisocoumarin moiety allowing thus both the accurate quantification of OTA and OT alpha and the establishing of a reliable detoxification rate.
• 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.