(3R)-3-甲基-2,5-哌嗪二酮 | 88547-15-3

• 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
• 中文名称: (3R)-3-甲基-2,5-哌嗪二酮
• 中文别名: (R)-3-甲基哌嗪-2,5-二酮
• 英文名称: 3-methyl-piperazine-2,5-dione
• 英文别名: 2,5-Piperazinedione, 3-methyl-, (3R)-；(3R)-3-methylpiperazine-2,5-dione
• CAS: 88547-15-3
• 化学式: C₅H₈N₂O₂
• 分子量: 128.131
• InChiKey: ICCHEGCKVBMSTF-GSVOUGTGSA-N

物化性质

• 熔点：
  247.5-249.5 °C
• 沸点：
  495.7±38.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  (3R)-3-甲基-2,5-哌嗪二酮 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (R)-(-)-2-甲基哌嗪
  参考文献：
  名称：

  Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride

  摘要：

  Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.

  DOI：

  10.1021/jm00105a025
• 作为产物：
  描述：

  Z-Gly-D-Ala-OMe 在 氢气 、 溶剂黄146 作用下， 生成 (3R)-3-甲基-2,5-哌嗪二酮
  参考文献：
  名称：

  Facile Synthesis of (2R,3R)-Phenylalanine-2,3-d₂and NMR Study on Deuterated Gramicidin S

  摘要：

  (2R,3R)-苯丙氨酸-2,3-d2 (d-Phe*)通过环(-(Z)-2,3-脱氢苯丙氨酰-d-丙氨酰-)在2H2气氛下催化还原和连续反应合成在高手性诱导下酸水解产率达80%。由此获得的d-Phe*用于合成[d-Phe*4,4']短杆菌肽S(GS*)。 DMSO-d6 中 GS* 的 1H NMR 谱显示 d-Phe* 残基的 (3S)-质子在 2.98 ppm 处有尖锐的单线态。有人提出，GS d-Phe 芳香族侧链的旋转异构体中，κ1=180° 的旋转异构体占主导地位。目前的观察结果为基于该提议的 d-Phe β-质子分配提供了可靠的证据。

  DOI：

  10.1246/bcsj.57.2193

文献信息

• Comparative study of synthetic approaches to 1-arylmethylenepyrazino[2,1-b]quinazoline-3,6-diones
  作者：Pilar Cledera、Carmen Avendaño、J.Carlos Menéndez

  DOI：10.1016/s0040-4020(98)00744-3

  日期：1998.10

  4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones (2) was studied. Four synthetic methods were compared, namely direct condensation with the product of the reaction between anthranilic acid and thionyl chloride, transformation into monothioiminoethers or monoiminoethers followed by reaction with anthranilic acid derivatives, and monoacylation with o-azidobenzoyl chloride followed by intramolecular aza-Wittig reaction

  研究了3-芳基亚甲基哌嗪-2，5-二酮（1）向1-芳基亚甲基-2，4-二氢-1 H-吡嗪并[ 2，1 - b ]喹唑啉-3，6-二酮（2）的转化。比较了四种合成方法，即直接与邻氨基苯甲酸和亚硫酰氯之间的反应产物缩合，转化为单硫亚氨基醚或单亚氨基醚，然后与邻氨基苯甲酸衍生物反应，与邻叠氮基苯甲酰氯单酰化，然后进行分子内aza-Wittig反应。通过后一种方法可获得最佳结果。
• Facile Synthesis of (2<i>R</i>,3<i>R</i>)-Phenylalanine-2,3-<i>d</i>₂and NMR Study on Deuterated Gramicidin S
  作者：Kenjiro Tanimura、Tetsuo Kato、Michinori Waki、Sannamu Lee、Yasushi Kodera、Nobuo Izumiya

  DOI：10.1246/bcsj.57.2193

  日期：1984.8

  (2R,3R)-Phenylalanine-2,3-d2 (d-Phe*) was synthesized through catalytic reduction of cyclo(-(Z)-2,3-dehydrophenylalanyl-d-alanyl-) under an atmosphere of 2H2 and successive acid hydrolysis in the yield of 80% in high chiral induction. The d-Phe* thus obtained was used for synthesis of [d-Phe*4,4′] gramicidin S (GS*). The 1H NMR spectrum of GS* in DMSO-d6 showed a sharp singlet at 2.98 ppm for the (3S)-proton of d-Phe* residue. It has been proposed that among rotamers of d-Phe aromatic side chain in GS the one with κ1=180° is predominant. The present observation provides sound evidence for assignments of d-Phe β-protons based on the proposal.

  (2R,3R)-苯丙氨酸-2,3-d2 (d-Phe*)通过环(-(Z)-2,3-脱氢苯丙氨酰-d-丙氨酰-)在2H2气氛下催化还原和连续反应合成在高手性诱导下酸水解产率达80%。由此获得的d-Phe*用于合成[d-Phe*4,4']短杆菌肽S(GS*)。 DMSO-d6 中 GS* 的 1H NMR 谱显示 d-Phe* 残基的 (3S)-质子在 2.98 ppm 处有尖锐的单线态。有人提出，GS d-Phe 芳香族侧链的旋转异构体中，κ1=180° 的旋转异构体占主导地位。目前的观察结果为基于该提议的 d-Phe β-质子分配提供了可靠的证据。
• Microwave-Promoted Total Synthesis of Puniceloid D for Modulating the Liver X Receptor
  作者：Young Jin Jung、Narges Hosseininasab、Jungjin Park、Soonsil Hyun、Jae-Kyung Jung、Jae-Hwan Kwak

  DOI：10.3390/molecules29020416

  日期：——

  A growing global health concern is metabolic syndrome, which is defined by low HDL, diabetes, hypertension, and abdominal obesity. Nuclear receptors are attractive targets for treatment of diseases associated with metabolic syndrome. Liver X receptors (LXRs) have become one of the most significant pharmacological targets among nuclear receptors. Multiple research studies emphasize the essential function of the liver X receptor (LXR) in the pathophysiology of metabolic syndrome. Puniceloid D, among natural products, demonstrated promising effects on LXRα. However, attempts at the total synthesis of natural products were faced with challenges, including long synthetic steps and low yields, requiring a more efficient approach. In this study, for the first time, we successfully synthesized puniceloid D through a seven-step process and conducted docking studies to gain a comprehensive understanding of the interactions involved in the binding of puniceloid D to LXR within different heterodimeric contexts. Our understanding of the pathophysiology of metabolic syndrome could be improved by these findings, which might assist with the development of novel treatment strategies.

  代谢综合征是一个日益受到全球关注的健康问题，代谢综合征的定义是低高密度脂蛋白、糖尿病、高血压和腹部肥胖。核受体是治疗代谢综合征相关疾病的诱人靶点。肝 X 受体（LXRs）已成为核受体中最重要的药理靶点之一。多项研究强调了肝 X 受体（LXR）在代谢综合征病理生理学中的重要功能。天然产品中的石榴子素 D 对 LXRα 具有良好的作用。然而，天然产物全合成的尝试面临着合成步骤长、产量低等挑战，需要更高效的方法。在本研究中，我们首次通过七步工艺成功合成了蓬莱素 D，并进行了对接研究，以全面了解蓬莱素 D 在不同异源二聚体背景下与 LXR 结合所涉及的相互作用。这些发现将有助于我们更好地了解代谢综合征的病理生理学，并有助于开发新的治疗策略。
• Inhibition of Aflatoxin Production in Aspergillus flavus by a Klebsiella sp. and Its Metabolite Cyclo(l-Ala-Gly)
  作者：Shohei Sakuda、Masaki Sunaoka、Maho Terada、Ayaka Sakoda、Natsumi Ishijima、Noriko Hakoshima、Kenichi Uchida、Hirofumi Enomoto、Tomohiro Furukawa

  DOI：10.3390/toxins16030141

  日期：——

  inhibited aflatoxin (AF) production by A. flavus. The bacterium, isolated and identified as Klebsiella aerogenes, was found to produce an AF production inhibitor. Cyclo(l-Ala-Gly), isolated from the bacterial culture supernatant, was the main active component. The aflatoxin production-inhibitory activity of cyclo(l-Ala-Gly) has not been reported. Cyclo(l-Ala-Gly) inhibited AF production in A. flavus

  在我们在花生上培养产黄曲霉毒素的实验中，我们意外地发现粘附在花生上的一种细菌强烈抑制黄曲霉产生黄曲霉毒素（AF）。该细菌被分离并鉴定为产气克雷伯氏菌，被发现能产生 AF 生成抑制剂。从细菌培养上清液中分离得到的环(L-Ala-Gly)是主要活性成分。环(L-Ala-Gly)的黄曲霉毒素产生抑制活性尚未见报道。 Cyclo(l-Ala-Gly) 抑制黄曲霉中 AF 的产生，而不影响其在液体培养基中的真菌生长，其效力比环(l-Ala-l-Pro) 更强。在已知的抑制 AF 产生的二酮哌嗪类化合物中，Cyclo(l-Ala-Gly) 具有最强的 AF 产生抑制活性。环(1-Ala-Gly)中的甲基部分被乙基、丙基或异丙​​基取代的相关化合物显示出比环(1-Ala-Gly)强得多的活性。与 (l-Ala-l-Pro) 不同，Cyclo(l-Ala-Gly) 不会抑制黄曲霉中的重组谷胱甘肽-S-转移酶
• Armarego, Wilfred L. F.; Schou, Henning; Waring, Paul, Journal of Chemical Research, Miniprint, 1980, # 4, p. 1951 - 1966
  作者：Armarego, Wilfred L. F.、Schou, Henning、Waring, Paul

  DOI：——

  日期：——