1,4-dimethylpiperazine-2,3,5-trione

• 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: 1,4-dimethylpiperazine-2,3,5-trione
• 化学式: C₆H₈N₂O₃
• 分子量: 156.141
• InChiKey: BVDZPASSANKIIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-dimethylpiperazine-2,3,5-trione 在 N,N-二甲基丙烯基脲 、 四氧化锇 、 三氟化硼乙醚 、 四丁基氟化铵 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 47.83h， 生成 (±)-hyalodendrin
  参考文献：
  名称：

  表二硫代二酮哌嗪的模块化构造。

  摘要：

  表二硫代二酮哌嗪类（ETP）具有非常多样的生物学活性，并引起了合成方面的极大关注。积极进行类似物的制备；然而，它们在结构上具有挑战性，并且需要更直接和模块化的方法来合成它们。为此，报道了双功能三酮哌嗪结构单元用于ETP的直接合成的效用。由烯醇化烷基化然后进行位点选择性亲核试剂加成组成的模块化策略使得能够精确合成（±）-透明质酸和一系列类似物。

  DOI：

  10.1021/acs.orglett.9b01770
• 作为产物：
  描述：

  N~1~,N~2~-二甲基甘氨酸酰胺 、 草酰氯 在 咪唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.83h， 以40%的产率得到1,4-dimethylpiperazine-2,3,5-trione
  参考文献：
  名称：

  表二硫代二酮哌嗪的模块化构造。

  摘要：

  表二硫代二酮哌嗪类（ETP）具有非常多样的生物学活性，并引起了合成方面的极大关注。积极进行类似物的制备；然而，它们在结构上具有挑战性，并且需要更直接和模块化的方法来合成它们。为此，报道了双功能三酮哌嗪结构单元用于ETP的直接合成的效用。由烯醇化烷基化然后进行位点选择性亲核试剂加成组成的模块化策略使得能够精确合成（±）-透明质酸和一系列类似物。

  DOI：

  10.1021/acs.orglett.9b01770

文献信息

• Chiral 1,2,3‐Triazolium Salt Catalyzed Asymmetric Mono‐ and Dialkylation of 2,5‐Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers
  作者：Ju‐Song Yang、Ka Lu、Chen‐Xiao Li、Zu‐Hang Zhao、Xiao‐Ming Zhang、Fu‐Min Zhang、Yong‐Qiang Tu

  DOI：10.1002/anie.202114129

  日期：2022.2.21

  Chiral spirocyclic-amide-derived triazolium salts were used as new phase-transfer organocatalysts for asymmetric alkylation to construct 2,5-diketopiperazine motifs containing one or two tetrasubstituted carbon centers in high yields with excellent cis-diastereoselectivity and enantioselectivity. Control experiments and DFT calculations revealed the possible reaction mechanism and the origins of the

  手性螺环酰胺衍生的三唑鎓盐被用作不对称烷基化的新型相转移有机催化剂，以高产率构建含有一个或两个四取代碳中心的 2,5-二酮哌嗪基序，具有优异的顺式-非对映选择性和对映选择性。对照实验和 DFT 计算揭示了可能的反应机理和异常非对映选择性和对映选择性的起源。
• Total Synthesis of (−)-Glionitrin A and B Enabled by an Asymmetric Oxidative Sulfenylation of Triketopiperazines
  作者：Nicolas R. Koning、Anders P. Sundin、Daniel Strand

  DOI：10.1021/jacs.1c10364

  日期：2021.12.22

  natural products. Herein, we report the first total syntheses of (−)-glionitrin A/B and revise the absolute configurations. Emerging from the study is a novel oxidative sulfenylation of triketopiperazines that enables asymmetric formation of dithiodiketopiperazines on sensitive substrates. The concise route paves the way for further studies on the potent antimicrobial and antitumor activities of glionitrin

  在其他非手性支架上不对称构建二硫代二酮哌嗪仍然是许多具有生物学意义的天然产物中遇到的关键合成挑战。在此，我们报告了 (-)-glionitrin A/B 的首次全合成并修改了绝对构型。该研究产生了一种新的三酮哌嗪氧化亚磺酰化，可以在敏感底物上不对称地形成二硫代二酮哌嗪。简洁的路线为进一步研究 glionitrin A 的强效抗菌和抗肿瘤活性以及 glionitrin B 抑制癌细胞侵袭能力的有趣能力铺平了道路。
• Peptide peroxyl radicals: base-induced superoxide radical ion elimination versus bimolecular decay. A pulse radiolysis and product study
  作者：Oliver J. Mieden、Man Nien Schuchmann、Clemens von Sonntag

  DOI：10.1021/j100117a026

  日期：1993.4

  Radiolytically generated OH radicals react with the cyclic dipeptides glycine anhydride (1) and alanine anhydride (2), forming a single type of peptide radical in each case by abstracting a carbon-bound H atom at the ring. In the case of sarcosine anhydride (3), besides the C(3) or C(6) H atoms (78%), the H atoms at the N-methyl groups are also targets of the OH radical attack (22%). In N2O/O2 (4:1 v/v) saturated solutions these peptide radicals add oxygen (k almost-equal-to 2 x 10(9) dm3 mol-1 s-1) to form the corresponding peroxyl radicals 6 (from 1), 7 (from 2), and 12 and 13 (from 3). The kinetics of O2.- elimination from the radicals 6 and 7 has been monitored by pulse radiolysis techniques. The pK(a) values of the peroxyl radicals 6 and 7 have been determined to be 10.8 and 11.2, respectively. The anions of these peroxyl radicals (6a and 7a) rapidly eliminate O2.- with the rate constants 1.6 x 10(5) and 3.7 x 10(6) s-1, respectively. In contrast, the spontaneous HO2. elimination reactions of the peroxyl radicals 6 and 7 are very slow, with rate constants of < 1 and approximately 0.5 s-1 as estimated from product analysis. The overall bimolecular decay rate constants of the cyclic dipeptide peroxyl radicals have been determined by pulse radiolysis measurements (2k(6) = 8.6 x 10(8) dm3 mol-1 s-1; 2k(7) = 1.6 x 10(8) dm3 mol-1 s-1; 2k(12/13) = 4.0 X 10(8) dm3 mol-1 s-1). The main products (G values) in the gamma radiolysis of glycine anhydride in N2O/O2-saturated solution at pH 6 are 3-hydroxy-2,5-dioxopiperazine (14) (3.5 x 10(-7) mol J-1), 2,3,5-trioxopiperazine (17) (1.6 X 10(-7) mol J-1), and 2,5-dioxo-2,3,4,5-tetrahydropyrazine (8) (0.4 x 10(-7) mol J-1). The product 8 is in equilibrium with its hydrate 14, which is again in equilibrium with its ring-opened form N-glyoxylyl glycinamide (16). In acidic solutions radical 6 decays essentially bimolecularly, giving equal amounts of 14 (present in an equilibrium mixture of 8, 14, and 16) and 17. In basic solutions 14 becomes the single main product as the OH--induced O2.- elimination reaction becomes much faster than the bimolecular decay. This is in good agreement with the yield of O2.- formation as monitored by its reaction with tetranitromethane under various pH conditions. With alanine anhydride (2), the main reaction under gamma radiolysis conditions even at pH 6 is still the OH--induced O2.- elimination reaction with 3-hydroxy-2,5-dioxo-3,6-dimethylpiperazine (15) as the single main product (G(15) = 4.7 x 10(-7) mol J-1). The major peroxyl radical in the sarcosine anhydride system (12) only decays bimolecularly either by self-termination or by cross-termination with the minor peroxy radical 13 (products at pH 6 in gamma radiolysis: 2,3,5-trioxo-1,4-dimethylpiperazine (20), G = 4.0 x 10(-7) mol J-1; 3-hydroxy-2,5-dioxo-1,4-dimethylpiperazine(21), G = 0.4 x 10(-7) mol J-1; 1-formyl-2,5-dioxo-4-methylpiperazine (22), G = 0.6 x 10(-7) mol J-1; and 2,5-dioxo-1-methylpiperazine (24), G = 0.6 x 10(-7) mol J-1). The O2.-elimination reaction of radical 13 is estimated to have a rate constant of < 5 s-1.
• A Modular Construction of Epidithiodiketopiperazines
  作者：Thomas N. Snaddon、Toya D. Scaggs、Colin M. Pearson、James W. B. Fyfe

  DOI：10.1021/acs.orglett.9b01770

  日期：2019.6.21

  activities and have attracted significant synthetic attention. The preparation of analogues is actively pursued; however, they are structurally challenging, and more direct and modular methods for their synthesis are desirable. To this end, the utility of a bifunctional triketopiperazine building block for the straightforward synthesis of ETPs is reported. A modular strategy consisting of enolate alkylation

  表二硫代二酮哌嗪类（ETP）具有非常多样的生物学活性，并引起了合成方面的极大关注。积极进行类似物的制备；然而，它们在结构上具有挑战性，并且需要更直接和模块化的方法来合成它们。为此，报道了双功能三酮哌嗪结构单元用于ETP的直接合成的效用。由烯醇化烷基化然后进行位点选择性亲核试剂加成组成的模块化策略使得能够精确合成（±）-透明质酸和一系列类似物。