(3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione | 74124-69-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione
• 英文别名: 3-benzylidene-6-isobutyl-piperazine-2,5-dione；cyclo<ΔPhe-Leu>；cyclo(dehydrophenylalanyl-L-leucyl)；(3Z,6S)-3-benzylidene-6-(2-methylpropyl)piperazine-2,5-dione
• CAS: 74124-69-9
• 化学式: C₁₅H₁₈N₂O₂
• 分子量: 258.32
• InChiKey: JYJCBJDZVMKEFV-VWLVURMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione 在 cell-free extract of Streptomyces albulus KO-23 作用下， 以 phosphate buffer 为溶剂， 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：

  Biosynthetic Intermediates of the Tetradehydro Cyclic Dipeptide Albonoursin Produced by Streptomyces albulus KO-23.

  摘要：

  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。

  DOI：

  10.7164/antibiotics.53.1257
• 作为产物：
  描述：

  N-carboxy Boc-Leu-ΔPhe anhydride 在 N-甲基吗啉 、 盐酸 作用下， 生成 (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione
  参考文献：
  名称：

  A New Route to (Z)-3-Alkylidene-(S)-6-alkyl-2,5-piperazinediones via N-Carboxy-a-dehydroamino Acid Anhydrides

  摘要：

  DOI：

  10.3987/r-1987-08-2087

文献信息

• 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
• Rational design and synthesis of unsaturated 2,5-dioxopiperazine derivatives as potential protein tyrosine kinase inhibitors
  作者：Wen-Ren Li、Shao-Zheng Peng

  DOI：10.1016/s0040-4039(98)01599-8

  日期：1998.10

  The first general method for the synthesis of a library of trifunctionalized (Z)-3-alkylidene-2,5-piperazinediones as potential protein tyrosine kinase inhibitors from commercially available amino compounds, alpha-keto acids and aldehydes using a novel cyclization/cleavage strategy on solid support is described. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
• The Albonoursin Gene Cluster of S. noursei
  作者：Sylvie Lautru、Muriel Gondry、Roger Genet、Jean-Luc Pernodet

  DOI：10.1016/s1074-5521(02)00285-5

  日期：2002.12

  Albonoursin [cyclo(DeltaPhe-DeltaLeu)], an antibacterial peptide produced by Streptomyces noursei, is one of the simplest representatives of the large diketopiperazine (DKP) family. Formation of alpha,beta unsaturations was previously shown to occur on cyclo(L-Phe-L-Leu), catalyzed by the cyclic dipeptide oxidase (CDO). We used CDO peptide sequence information to isolate a 3.8 kb S. noursei DNA fragment that directs albonoursin biosynthesis in Streptomyces lividans. This fragment encompasses four complete genes: albA and albB, necessary for CDO activity; albC, sufficient for cyclic dipeptide precursor formation, although displaying no similarity to non ribosomal peptide synthetase (NRPS) genes; and albD, encoding a putative membrane protein. This first isolated DKP biosynthetic gene cluster should help to elucidate the mechanism of DKP formation, totally independent of NRPS, and to characterize novel DKP biosynthetic pathways that could be engineered to increase the molecular diversity of DKP derivatives.
• 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。
• A New Route to (Z)-3-Alkylidene-(S)-6-alkyl-2,5-piperazinediones via N-Carboxy-a-dehydroamino Acid Anhydrides
  作者：Chung-gi Shin、Yasuchika Yonezawa、Kazumichi Ogawa

  DOI：10.3987/r-1987-08-2087

  日期：——