(3Z,6Z)-3-(2-甲基丙亚基)-6-(苯基亚甲基)哌嗪-2,5-二酮 | 1222-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: (3Z,6Z)-3-(2-甲基丙亚基)-6-(苯基亚甲基)哌嗪-2,5-二酮
• 英文名称: (3Z,6Z)-3-benzylidene-6-(2-methylpropenyl)piperazine-2,5-dione
• 英文别名: (Z)-3-isobutylidene-(Z)-6-benzylidene-2,5-piperazinedione；albonoursin；albonursin；3-benzylidene-6-isobutylidene-piperazine-2,5-dione；Albonoursin, 3-Benzyliden-6-isobutyliden-piperazin-2,5-dion；(3Z,6Z)-3-benzylidene-6-(2-methylpropylidene)piperazine-2,5-dione
• CAS: 1222-90-8
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: LCIIOYPBHIZBOD-JMVBYTIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  (3Z,6Z)-3-(2-甲基丙亚基)-6-(苯基亚甲基)哌嗪-2,5-二酮 、 碘甲烷 在 sodium hydride 作用下， 反应 1.0h， 以72%的产率得到1,4-dimethyl-(Z)-3-isobutylidene-(Z)-6-benzylidene-2,5-piperazinedione
  参考文献：
  名称：

  Shin, Chung-gi, Heterocycles, 1983, vol. 20, # 7, p. 1407 - 1433

  摘要：

  DOI：
• 作为产物：
  描述：

  苯甲醛 在 potassium fluoride on basic alumina 作用下， 生成 (3Z,6Z)-3-(2-甲基丙亚基)-6-(苯基亚甲基)哌嗪-2,5-二酮
  参考文献：
  名称：

  Villemin, Didier; Alloum, Abdelkrim Ben, Synthetic Communications, 1990, vol. 20, # 21, p. 3325 - 3331

  摘要：

  DOI：

文献信息

• Biosynthetic Intermediates of the Tetradehydro Cyclic Dipeptide Albonoursin Produced by Streptomyces albulus KO-23.
  作者：HIROSHI KANZAKI、SATOHIRO YANAGISAWA、TERUHIKO NITODA

  DOI：10.7164/antibiotics.53.1257

  日期：——

  The cell-free extract of an albonoursin-producing strain Streptomyces albulus KO-23 catalyzes the conversion of cyclo(L-Leu-L-Phe) (1) to albonoursin (2). At the early stage of this conversion, two compounds were newly formed prior to albonoursin synthesis in the reaction mixture. These compounds were isolated and identified as (Z)-3-benzylidene-6-isobutyl-2, 5-piperazinedione (4) and (Z)-3-benzyl-6-isobutylidene-2, 5-piperazineclione (3). The cell-free extract also catalyzed the conversion of compound 3 or 4 to albonoursin. From these results, albonoursin was found to be biosynthesized via these compounds from cyclo(L-Leu-L-Phe). These didehydro diketopiperazines exhibited no inhibitory activity toward the first cleavage of sea urchin embryo in contrast to the higher cytotoxicity for albonoursin, indicating that dehydrogenation at α, β-positions of both amino acid residues in diketopiperazines is required for cytotoxicity.

  一株产阿尔博诺辛的链霉菌Streptomyces albulus KO-23的无细胞提取物催化了环状(L-Leu-L-Phe) (1) 转化为阿尔博诺辛 (2)。在该转化的早期阶段，反应体系中新形成了两个化合物，这两个化合物被分离并鉴定为(Z)-3-苄叉-6-异丁基-2, 5-哌嗪二酮 (4)和(Z)-3-苄-6-异丁烯基-2, 5-哌嗪二酮 (3)。无细胞提取物还催化了化合物3或4转化为阿尔博诺辛。从这些结果来看，阿尔博诺辛的生物合成是通过这些化合物由环状(L-Leu-L-Phe)转化而来的。这些二去氢二酮哌嗪对海胆胚胎的第一次裂变没有抑制活性，而阿尔博诺辛则具有更高的细胞毒性，表明在二酮哌嗪中α、β位的氨基酸残基去氢化是细胞毒性的必要条件。
• Effective Production of Dehydro Cyclic Dipeptide Albonoursin Exhibiting Pronuclear Fusion Inhibitory Activity. II. Biosynthetic and Bioconversion Studies.
  作者：HIROSHI KANZAKI、DAISUKE IMURA、TERUHIKO NITODA、KAZUYOSHI KAWAZU

  DOI：10.7164/antibiotics.53.58

  日期：——

  Albonoursin production was greatly enhanced when cyclo (L-Leu-L-Phe) (CFL), a tetrahydro derivative of albonoursin, was added to the 2-day culture of an albonoursinproducing actinomycete, Streptomyces albulus KO-23. The increase in albonoursin production paralleled the amount of CFL added. Furthermore, the resting cells of the strain catalyzed the bioconversion of CFL to albonoursin. The optimum pH and temperature for the conversion were found to be pH 10.0 and 50°C. The feeding experiments and the resting-cell reactions revealed that albonoursin is biosynthesized by dehydrogenation of CFL in the actinomycete. This is the first report for a dehydrogenation of amino acid residues at the α, β-positions in cyclic dipeptides.

  在产甲氧苄啶的放线菌--白链霉菌 KO-23 的 2 天培养物中加入环（L-Leu-L-Phe）（CFL）（一种甲氧苄啶的四氢衍生物），可大大提高甲氧苄啶的产量。随着 CFL 添加量的增加，白僵菌素产量也随之增加。此外，该菌株的静止细胞还能催化 CFL 向甲苯硫酚的生物转化。转化的最佳 pH 值和温度分别为 pH 值 10.0 和 50°C。喂养实验和静止细胞反应表明，白头翁素是通过放线菌中的 CFL 脱氢作用进行生物合成的。这是首次报道环状二肽中 α、β 位氨基酸残基的脱氢反应。
• 2,5-Diketopiperazine Derivatives as Potential Anti-Influenza (H5N2) Agents: Synthesis, Biological Evaluation, and Molecular Docking Study
  作者：Chanakan Winyakul、Weerachai Phutdhawong、Poomipat Tamdee、Jitnapa Sirirak、Thongchai Taechowisan、Waya S. Phutdhawong

  DOI：10.3390/molecules27134200

  日期：——

  2,5-Diketopiperazine derivatives, consisting of benzylidene and alkylidene substituents at 3 and 6 positions, have been considered as a core structure for their antiviral activities. Herein, the novel N-substituted 2,5-Diketopiperazine derivatives were successfully prepared and their antiviral activities against influenza virus were evaluated by monitoring viral propagation in embryonated chicken eggs. It was found that (3Z,6Z)-3-benzylidene-6-(2-methyl propylidene)-4-substituted-2,5-Diketopiperazines (13b–d), (3Z,6E)-3-benzylidene-6-(2-methylpropyli dene)-1-(1-ethyl pyrrolidine)-2,5-Diketopiperazine (14c), and Lansai-C exhibited negative results in influenza virus propagation at a concentration of 25 µg/mL. Additionally, molecular docking study revealed that 13b–d and 14c bound in 430-cavity of neuraminidase from H5N2 avian influenza virus and the synthesized derivatives also strongly interacted with the key amino acid residues, including Arg371, Pro326, Ile427, and Thr439.

  2,5-二酮哌嗪衍生物是由苯甲醛和烷基甲醛取代3和6位置而成的核心结构，具有抗病毒活性。本研究成功合成了新型N取代的2,5-二酮哌嗪衍生物，并通过监测在鸡胚中的病毒传播评估了它们对流感病毒的抗病毒活性。结果发现，在25 µg/mL浓度下，(3Z,6Z)-3-苯甲醛基-6-(2-甲基丙烯基)-4-取代-2,5-二酮哌嗪衍生物(13b–d)、(3Z,6E)-3-苯甲醛基-6-(2-甲基丙烯基)-1-(1-乙基吡咯烷)-2,5-二酮哌嗪衍生物(14c)和Lansai-C在流感病毒传播方面呈现负效果。此外，分子对接研究揭示出13b–d和14c在H5N2禽流感病毒神经氨酸酶的430腔中结合，并且合成的衍生物也与关键氨基酸残基（包括Arg371、Pro326、Ile427和Thr439）强烈相互作用。
• Cyclic dipeptide oxidase from Streptomyces nourseiIsolation, purification and partial characterization of a novel, amino acyl alpha,beta-dehydrogenase
  作者：Muriel Gondry、Sylvie Lautru、Guillaume Fusai、Gilles Meunier、Andre Menez、Roger Genet

  DOI：10.1046/j.1432-1033.2001.02038.x

  日期：2001.3

  Cyclic dipeptide oxidase is a novel enzyme that specifically catalyzes the formation of alpha,beta-dehydro-Phe (Delta Phe) and alpha,beta-dehydro-Leu (Delta Leu) residues during the biosynthesis of albonoursin, cyclo(Delta Phe-Delta Leu), an antibiotic produced by Streptomyces noursei. It was purified 600-fold with a 30% overall recovery, and consists of the association of a single type of subunit

  环二肽氧化酶是一种新型酶，可在生物素，环（Delta Phe-Delta Leu）的生物合成过程中特异性催化α，β-脱氢-Phe（Delta Phe）和α，β-脱氢-Leu（Delta Leu）残基的形成。 ），是由链霉菌产生的抗生素。它被纯化了600倍，总回收率为30％，由单一类型的亚基与相对分子质量21,066的缔合组成，导致相对分子质量超过2,000,000的大均聚物。该酶表现出典型的黄素蛋白光谱，其最大值在343.5和447.5 nm处，黄素修复基团与该蛋白共价结合。天然底物环（L-Phe-L-Leu）的催化反应发生在两步顺序反应中，该反应首先导致环（α，β-脱氢-Phe-L-Leu），最后导致白铁蛋白。确定第一步的动力学参数（K（m）= 53 microM; k = 0.69 s（-1））。该酶已显示出催化多种环（二肽）的转化的作用，并且可以通过产生H（2）O（2）来以分子氧为代
• VILLEMIN, DIDIER;ALLOUM, ABDELKRIM BEN, SYNTH. COMMUN., 20,(1990) N1, C. 3325-3331
  作者：VILLEMIN, DIDIER、ALLOUM, ABDELKRIM BEN

  DOI：——

  日期：——