梭孢壳素B | 71950-67-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 中文名称: 梭孢壳素B
• 中文别名: 二锰(2+)[2-(磷羧酸根氧代)乙基]磷羧酸酯四水合物
• 英文名称: thielavin B
• 英文别名: 4-[4-(2,4-dihydroxy-3,6-dimethylbenzoyl)oxy-2-methoxy-3,5,6-trimethylbenzoyl]oxy-2-methoxy-3,5,6-trimethylbenzoic acid
• CAS: 71950-67-9
• 化学式: C₃₁H₃₄O₁₀
• 分子量: 566.605
• InChiKey: UULGWGARYDGVBM-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：可溶； DMSO：可溶；乙醇：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  149
• 氢给体数：
  3
• 氢受体数：
  10

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  梭孢壳素B 在 sodium acetate 、 三氟乙酸 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (4-Benzhydryloxycarbonyl-3-methoxy-2,5,6-trimethylphenyl) 4-[2,4-dihydroxy-3,6-dimethyl-5-[(2-oxo-2-phenylmethoxyethyl)iminomethyl]benzoyl]oxy-2-methoxy-3,5,6-trimethylbenzoate
  参考文献：
  名称：

  Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives

  摘要：

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.

  DOI：

  10.1021/jm960437a

文献信息

• Thielavins as Glucose-6-phosphatase (G6Pase) Inhibitors: Producing Strain, Fermentation, Isolation, Structural Elucidation and Biological Activities.
  作者：SHINICHI SAKEMI、HIDEO HIRAI、TOSHIO ICHIBA、TAISUKE INAGAKI、YOSHINAO KATO、NAKAO KOJIMA、HIROYUKI NISHIDA、JANICE C. PARKER、TOSHIYUKI SAITO、HIROKO TONAI-KACHI、MARIA A. VANVOLKENBURG、NOBUJI YOSHIKAWA、YASUHIRO KOJIMA

  DOI：10.7164/antibiotics.55.941

  日期：——

  High-throughput screening of microbial extracts using rat hepatic microsomal glucose-6-phosphatase (G6Pase) led us to find thielavin B as a G6Pase inhibitor with inhibition of glucose output from glucagon-stimulated hepatocytes. Further searching for more potent analogs identified 11 new thielavins F-P in addition to the known thielavins A and B from a fungus Chaetomium carinthiacum ATCC 46463. Thielavin G showed the strongest activity as a G6Pase inhibitor (IC50=0.33μM), while the IC50 of thielavin B was 5.5μM. According to the structureactivity relationship, including authentic thielavins C, D and 3 partial hydrolysates from thielavins A and B, 3 benzoic acid-units and carboxylic acid functions are essential for G6Pase inhibition.

  使用大鼠肝微粒体葡萄糖-6-磷酸酶（G6Pase）对微生物提取物进行高通量筛选，我们发现thielavin B是一种G6Pase抑制剂，可抑制胰高血糖素刺激肝细胞产生的葡萄糖。进一步寻找更有效的类似物，除了已知来自真菌Chaetomium carinthiacum ATCC 46463的thielavin A和B外，还发现了11种新的thielavin F-P。Thielavin G作为G6Pase抑制剂表现出最强的活性（IC50=0.33μM），而thielavin B的IC50为5.5μM。根据结构活性关系，包括真正的thielavin C、D和来自thielavin A和B的3个部分水解产物，3个苯甲酸单元和羧酸功能对于G6Pase抑制至关重要。