1-acetyl-3-(2,4,5-trimethoxy-3-methylphenyl)methyl-2,5-piperazinedione | 113296-72-3

• 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
• 英文名称: 1-acetyl-3-(2,4,5-trimethoxy-3-methylphenyl)methyl-2,5-piperazinedione
• 英文别名: 1-acetyl-3-(2,4,5-trimethoxy-3-methylphenylmethyl)-2,5-piperazinedione；1-Acetyl-3-[(2,4,5-trimethoxy-3-methylphenyl)methyl]piperazine-2,5-dione
• CAS: 113296-72-3
• 化学式: C₁₇H₂₂N₂O₆
• 分子量: 350.371
• InChiKey: PJVJBMMXJRREAX-UHFFFAOYSA-N

物化性质

• 熔点：
  116-118 °C
• 沸点：
  583.6±50.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-acetyl-3-(2,4,5-trimethoxy-3-methylphenyl)methyl-2,5-piperazinedione 在 potassium tert-butylate 、 sodium hydride 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 46.17h， 生成 (Z)-1-acetyl-5-benzyloxy-6-(2,4,5-trimethoxy-3-methylphenylmethyl)-3-(2,4,5-trimethoxy-3-methylphenylmethylene)-1,2,3,6-tetrahydropyrazin-2-one
  参考文献：
  名称：

  Preparations and reactions of (Z)-3-arylidene-6-arylmethyl-2,5-piperazinediones having highly oxygenated benzene rings.

  摘要：

  本研究描述了多种具有高含氧苯环的 (Z) -3-亚芳基-6-芳基甲基-2, 5-哌嗪二酮 10 的简单高效合成，以及位置 4 的区域选择性苄基化。

  DOI：

  10.1248/cpb.35.2525
• 作为产物：
  描述：

  2,4,5-三甲氧基苯甲醛 在 palladium on activated charcoal 正丁基锂 、 四甲基乙二胺 、 potassium tert-butylate 、 氢气 、 氯化铵 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 22.67h， 生成 1-acetyl-3-(2,4,5-trimethoxy-3-methylphenyl)methyl-2,5-piperazinedione
  参考文献：
  名称：

  Improvements in Aldol Reactions with Diketopiperazines

  摘要：

  Precipitation of products by using dichloromethane as solvent permits an efficient aldol-type reaction between 1,4-diacetyl-2,5-piperazinedione and aromatic aldehydes catalyzed by K'BuO/'BuOH independently of the electrophilic character of the aryl ring. A simple method to obtain 3-methyl-2,4,5-trimethoxybenzaldehyde is also reported.

  DOI：

  10.1081/scc-120030746

文献信息

• Pictet Spengler-type reactions in 3-arylmethylpiperazine-2,5-diones. Synthesis of pyrazinotetrahydroisoquinolines
  作者：Juan Francisco González、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/j.tet.2004.05.073

  日期：2004.7

  of aldehydes and acetals as N-alkylating agents of 1-acetyl-3-arylmethylpiperazine-2,5-diones and the subsequent cyclization of the N-alkylated products was studied. Use of paraformaldehyde in different reaction conditions gave 6-unsubstituted 3,6,11,11a-tetrahydro-2H-pyrazino[1,2-b]isoquinoline-1,4-diones and, in some cases, benzo[f]pyrazino[1,2-c]1,3-oxazepine-1,4-diones. Succesful reactions with

  研究了醛和缩醛作为1-乙酰基-3-芳基甲基哌嗪-2，5-二酮的N-烷基化剂的行为以及随后N-烷基化产物的环化。在不同的反应条件下使用低聚甲醛得到6-未取代的3,6,11,11a-四氢-2 H-吡嗪并[1,2 - b ]异喹啉-1,4-二酮，在某些情况下还会得到苯并[ f ]吡嗪并[1,2 - c ] 1,3-氧杂氮杂-1,4-二酮。与苯甲醛的成功反应需要首先活化内酰胺功能，并用醛二甲基乙缩醛催化N-烷基化。孤立的O，N将如此获得的酰胺基乙缩醛进行非对映选择性的Pictet Spengler型反应，该反应与在几个环活化度的芳烃和噻吩一起产生6-苯基吡嗪并异喹啉二酮和相应的噻吩类似物。
• Synthesis of phthalascidin analogs
  作者：J. Francisco González、Loreto Salazar、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/j.tet.2005.05.068

  日期：2005.8

  We report a new approach to obtain phthalascidin analogs. 6-Phthalimidomethylpyrazino[1,2-b]isoquinoline-1,4-dione (5a) was obtained in a one-pot N-alkylation/cyclization of the corresponding 1-acetyl-3-arylmethyl-2,5-piperazinedione with N-phthalylacetaldehyde dimethyl acetal. Chemoselective reduction of the C(1)-carbonyl group in the 3-arylmethyl-11,11a-dehydroderivative 9a was followed by cyclization

  我们报告了一种获得邻苯二酚类似物的新方法。6- Phthalimidomethylpyrazino [1,2 b ]异喹啉-1,4-二酮（5A）在一锅得到Ñ烷基化相应的1-乙酰基-3-芳甲基-2,5-哌嗪二酮与/环化Ñ -邻苯二甲酰乙醛二甲基乙缩醛。对3-芳基甲基-11,11a-脱氢衍生物9a中的C（1）-羰基进行化学选择性还原，然后将酰基中间体中间体环化，得到6,15-亚氨基-7-氧代-14,14a-脱氢异喹啉[3，2 - b ] 3-苯扎佐星11a。或者，八环化合物13a 通过对C（1）-羰基和一个邻苯二甲酰亚胺羰基进行了还原的前体进行新型双环化反应，得到了α-烯烃。
• Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H)
  作者：Masashi Yokoya、Keiichiro Kobayashi、Mitsuhiro Sato、Naoki Saito

  DOI：10.3390/md13084915

  日期：——

  The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño's

  描述了从印度明亮的蓝色海绵嗜盐菌中分离出的（±）-肾上腺素I的第一个全合成。关键步骤是对五环双-对醌衍生物（3）进行立体选择性和区域选择性氧化硒氧化。我们还报告了基于Avendaño方案在早期阶段通过C3-C4双键形成大规模合成cribrostatin 4（renieramycin H）的方法，该方法是从现成的1-乙酰-3-（3-甲基-2,4） 18步制备1，5-三甲基苯基）甲基-哌嗪-2,5-二酮（8）（总产率8.3％）。该合成提供了明确的证据来支持雷尼霉素I的原始结构。
• Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties
  作者：Irene Ortín、Juan Francisco González、Elena de la Cuesta、Cristina Manguan-García、Rosario Perona、Carmen Avendaño

  DOI：10.1016/j.bmc.2008.07.083

  日期：2008.10

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthetic Studies on Saframycin Anibiotics: An Improved Synthesis of Tricyclic Lactam Intermediate and Construction of the Core Ring System of Saframycin A
  作者：Naoki Saito、Shinya Kimura、Shintaro Kawai、Masayuki Azuma、Yu-ichi Koizumi、Masashi Yokoya、Yoshifumi Umehara

  DOI：10.3987/com-14-s(k)24

  日期：——

  An improved synthesis of the tricyclic lactam intermediate of saframycin antibiotics and the construction of the core ring system having a cyano group at C-21 position were presented.(1) The stereochemistry of several key intermediates was determined by X-ray crystallographic analysis.