硫赭曲菌素 | 519-57-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 硫赭曲菌素
• 英文名称: sulochrin
• 英文别名: methyl 2-(2,6-dihydroxy-4-methylbenzoyl)-5-hydroxy-3-methoxybenzoate；sulochrine；2-(2,6-dihydroxy-4-methyl-benzoyl)-5-hydroxy-3-methoxy-benzoic acid methyl ester；2-(2,6-Dihydroxy-4-methyl-benzoyl)-5-hydroxy-3-methoxy-benzoesaeure-methylester
• CAS: 519-57-3
• 化学式: C₁₇H₁₆O₇
• 分子量: 332.31
• InChiKey: YJRLSCDUYLRBIZ-UHFFFAOYSA-N

物化性质

• 熔点：
  242-248 °C (decomp)
• 沸点：
  576.3±50.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)
• 溶解度：
  在DMF中可溶

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2918990090
• 储存条件：
  存储条件：2-8℃，密封保存，置于干燥处。

制备方法与用途

舒乐菌素是由金黄色土曲霉产生的代谢产物。它具有抗菌活性。

反应信息

• 作为反应物：
  描述：

  硫赭曲菌素 在 氢氧化钾 作用下， 生成 1,6-Dihydroxy-3-methylxanthon-8-carbonsaeure
  参考文献：
  名称：

  Nishikawa, Acta Phytochimica, 1939, vol. 11, p. 167,179

  摘要：

  DOI：
• 作为产物：
  描述：

  3-(苄氧基)-5-羟基苯甲酸甲酯 在 吡啶 、 palladium dihydroxide 、 potassium permanganate 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 重铬酸吡啶 、 正丁基锂 、 Bu₄(NH₄) 、 potassium carbonate 、 三苯基膦 、 环己烯 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 硫赭曲菌素
  参考文献：
  名称：

  Effects of ortho-substituent groups of sulochrin on inhibitory activity to eosinophil degranulation

  摘要：

  Sulochrin, a metabolite of fungi, has been shown to have an inhibitory activity to eosinophil degranulation. A series of sulochrin derivatives substituted at ortho-positions to the 10-carbonyl group was examined the activity. The importance of alkylester at C-6 position and several chemical properties of substituted groups at ortho-positions to exhibit activity are described. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00305-4

文献信息

• Studies on metabolites produced by Aspergillus terreus var. aureus. I. Chemical structures and antimicrobial activities of metabolites isolated from culture broth.
  作者：YOSHIHIKO INAMORI、YOSHIAKI KATO、MAYURI KUBO、TERUO KAMIKI、TSUNEMATSU TAKEMOTO、KYOSUKE NOMOTO

  DOI：10.1248/cpb.31.4543

  日期：——

  A fungus which was identified as Aspergillus terreus var. aureus showed antifungal and antibacterial activities. Through the investigation of its metabolites, six compounds (1-6) were isolated ; emodin (1), dihydrogeodin (2), questin (3), sulochrin (5), the new metabolite 2-(3-chloro-4-methyl-γ-resorcyloyl)-5-hydroxy-m-anisic acid methyl ester (4), which is a monochloro derivative of sulochrin (5), and compound (6), the chemical structure of which has not yet been clarified. Dihydrogeodin (2), sulochrin (5), 4 and 6 showed antifungal and antibacterial activities, and 6 had especially strong antifungal activity towards Trichophyton mentagrophytes.

  经鉴定，该真菌为土曲霉变种，具有抗真菌和抗细菌活性。通过对其代谢物的研究，分离出了六种化合物（1-6）：大黄素（1）、二氢大黄素（2）、喹啉（3）、舒洛钦（5）、新代谢物 2-(3-氯-4-甲基-γ-去甲环基)-5-羟基-间甲氧基苯甲酸甲酯（4）（是舒洛钦（5）的单氯衍生物）以及化合物（6），后者的化学结构尚未明确。二氢鬼臼毒素（2）、舒洛钦（5）、4 和 6 具有抗真菌和抗细菌活性，其中 6 对脑毛癣菌具有特别强的抗真菌活性。
• Purification and Characterization of Sulochrin Oxidase from Penicillium frequentans.
  作者：Kexue HUANG、Yasunori YOSHIDA、Kazunobu MIKAWA、Isao FUJII、Yutaka EBIZUKA、Ushio SANKAWA

  DOI：10.1248/bpb.19.42

  日期：——

  Sulochrin oxidase, an enzyme catalyzing regio- and stereospecific phenol oxidative coupling reaction to form (+)-bisdechlorogeodin from sulochrin, was isolated from Penicillium frequentans CMI 96659. By chromatographies on DEAE-cellulose, hydroxyapatite, Phenyl-Sepharose, Mono P, Mono Q, and HPLC gel filtration columns, sulochrin oxidase was purified to apparent homogeneity. The purified enzyme had a molecular weight of 230 K as estimated by gel filtration and 110 K as estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis under denaturing conditions, suggesting that the active enzyme was a homodimer. The enzyme showed pI 4.0 and an optimum pH of 6. The enzyme activity was strongly inhibited by the copper-chelating reagent, diethyldithiocarbamate, and did not recover its full activity even after removing the inhibitor by dialysis. However, enzyme activity was fully restored by the addition of Cu2+. Thus, sulochrin oxidase is considered to be a copper protein. The enzyme showed high substrate specificity for benzophenone compounds such as sulochrin and dihydrogeodin.

  Sulochrin 氧化酶是一种催化区域特异性和立体特异性苯酚氧化偶联反应的酶，可从 Sulochrin 中形成 (+)-双脱氯乔丁 (Penicillium permanentans CMI 96659)。通过 DEAE-纤维素、羟基磷灰石、Phenyl-Sepharose、Mono P、Mono Q 色谱分析，并用HPLC凝胶过滤柱，将sulochrin氧化酶纯化至表观同质性。纯化酶的分子量通过凝胶过滤估计为230 K，通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳在变性条件下估计分子量为110 K，这表明活性酶是同型二聚体。该酶的pI为4.0，最适pH为6。该酶活性受到铜螯合剂二乙基二硫代氨基甲酸盐的强烈抑制，即使通过透析除去抑制剂后也没有恢复其全部活性。然而，添加 Cu2+ 后酶活性完全恢复。因此，硫氯蛋白氧化酶被认为是一种铜蛋白。该酶对二苯甲酮化合物（如 Sulochrin 和二氢地黄素）表现出高底物特异性。
• [EN] PHOTO INDUCED CONTROL OF PROTEIN DESTRUCTION<br/>[FR] CONTRÔLE PHOTO-INDUIT DE DESTRUCTION DE PROTÉINES
  申请人：BETH ISRAEL DEACONESS MEDICAL CT INC

  公开号：WO2021016521A1

  公开（公告）日：2021-01-28

  By hijacking endogenous E3 ligase to degrade protein targets via the ubiquitin-proteasome system, PROTACs (PRoteolysis TArgeting Chimeras) provide a new strategy to inhibit protein targets that were previously regarded as undruggable. The compounds described herein comprise a photolabile group on PROTACs, enabling the degradation of protein targets in a spatiotemporally controlled manner. By adding a photolabile caging group on ubiquitin recruiting moieties, light-inducible protein degradation was acheived. These opto-PROTACs display no activity in the dark, while restricted degradation can be induced at a specific time and rate by UVA-irradiation. Accordingly, these compounds provide light-controlled PROTACs and methods of using such compounds.

  通过劫持内源性E3连接酶，通过泛素-蛋白酶体系统降解蛋白靶标，PROTACs（蛋白质降解靶向嵌合物）提供了一种新的策略，以抑制先前被认为无法治疗的蛋白靶标。本文所述的化合物包括在PROTACs上的光敏基团，以使蛋白靶标以时空控制的方式降解。通过在泛素招募基团上添加光敏囚禁基团，实现了光诱导的蛋白质降解。这些光控PROTACs在暗处没有活性，而可以通过紫外线照射在特定时间和速率下诱导限制性降解。因此，这些化合物提供了光控制的PROTACs和使用这些化合物的方法。
• [EN] PROTEOLYSIS TARGETING CHIMERA COMPOUNDS AND METHODS OF PREPARING AND USING SAME<br/>[FR] COMPOSÉS CHIMÈRES DE CIBLAGE DE PROTÉOLYSE ET PROCÉDÉS DE PRÉPARATION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV YALE

  公开号：WO2017079267A1

  公开（公告）日：2017-05-11

  The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

  本发明涉及新型化合物和方法，用于预防或治疗与主题需要的酪氨酸激酶过度表达和/或无控制激活相关和/或引起的疾病。在某些实施例中，本发明的化合物包括酪氨酸激酶抑制剂、连接剂和泛素连接酶结合剂。本发明的方法包括向主题给予本发明中至少一种化合物的药物有效量。
• Crystal Structures of Sulochrin Derivatives.
  作者：Akihiro UENO、Hiroshi OHASHI、Toyoo NAKANO、Kaname KIMURA、Toshiyuki SHIMIZU、Toshio HAKOJIMA、Hiroshi IIJIMA

  DOI：10.1248/cpb.46.1929

  日期：——

  The crystal structures of sulochrin derivatives, sulochrin triacetate (2) and sulochrin 4-(4'-bromobenzoate) (3), were determined. Triacetyl derivative 2 was in a conformation where the planes of two aromatic rings and the central carbonyl plane were all oblique to each other. Compound 3 was in a conformation where ring B and the central carbonyl planes were co-planar and crossed at a right angle to ring A plane, suggesting the effect of substituents at ortho positions on conformation of tetra ortho substituted benzophenones.

  研究人员测定了舒洛清衍生物三乙酸舒洛清酯（2）和舒洛清 4-(4'-溴苯甲酸酯)（3）的晶体结构。三乙酸酯衍生物 2 的构象是两个芳香环的平面和中心羰基平面相互倾斜。化合物 3 的构象是环 B 和中心羰基平面共面，并与环 A 平面成直角交叉，这表明正交位置的取代基对四正交取代二苯甲酮的构象有影响。