(2S,5S)-2-hydroxymethyl-5-iso-butyl-3,6-diketopiperazine | 65519-48-4

• 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: (2S,5S)-2-hydroxymethyl-5-iso-butyl-3,6-diketopiperazine
• 英文别名: 3-hydroxymethyl-6-(2-methylpropyl)-2,5-diketopiperazine；cyclo(L-Leu-L-Ser)；cyclo(Ser-Leu)；cyclo(leu-ser)；(3S,6S)-3-(hydroxymethyl)-6-(2-methylpropyl)piperazine-2,5-dione
• CAS: 65519-48-4
• 化学式: C₉H₁₆N₂O₃
• 分子量: 200.238
• InChiKey: ANLAGVXTPHOKLD-BQBZGAKWSA-N

物化性质

• 沸点：
  509.4±35.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,5S)-2-hydroxymethyl-5-iso-butyl-3,6-diketopiperazine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 92.0h， 生成 (2R,5S)-2-Hydroxymethyl-5-isobutyl-piperazine-1,4-dicarboxylic acid di-tert-butyl ester
  参考文献：
  名称：

  General and Versatile Approach to the Synthesis of Optically Active 5- Alkylpiperazine-2-carboxylic Acids

  摘要：

  描述了光学活性5-烷基哌嗪-2-羧酸的一般和便利合成方法。该方法基于L-或D-丝氨酸与α-氨基酸的环化反应，并且在反应过程中保持光学纯度不变。所述程序基于易于获得的起始材料，并可以安排用于多克量的合成。

  DOI：

  10.1055/s-1994-25484
• 作为产物：
  描述：

  N-苄氧羰基-L-亮氨酸 在 palladium on activated charcoal N-甲基吗啉 、 环己烷 、 thylchlorophormate 作用下， 以 乙酸乙酯 为溶剂， 反应 128.0h， 生成 (2S,5S)-2-hydroxymethyl-5-iso-butyl-3,6-diketopiperazine
  参考文献：
  名称：

  General and Versatile Approach to the Synthesis of Optically Active 5- Alkylpiperazine-2-carboxylic Acids

  摘要：

  描述了光学活性5-烷基哌嗪-2-羧酸的一般和便利合成方法。该方法基于L-或D-丝氨酸与α-氨基酸的环化反应，并且在反应过程中保持光学纯度不变。所述程序基于易于获得的起始材料，并可以安排用于多克量的合成。

  DOI：

  10.1055/s-1994-25484

文献信息

• Chiral ligands containing heteroatoms. 11. Optically active 2-hydroxymethyl piperazincs as catalysts in the enantioselective addition of diethylzinc to benzaldehyde
  作者：Massimo Falorni、Michele Satta、Sandra Conti、Giampaolo Giacomelli

  DOI：10.1016/s0957-4166(00)80107-x

  日期：1993.11

  (2R,5S) and (2S,5S)-2-hydroxymethyl-5-alkyl piperazines 1–5 were prepared in good yields without any racemization. The use of these compounds as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes is described. This paper reports the first example of the use of piperazine methanols in asymmetric synthesis.

  从对映体纯的丝氨酸开始，以高收率制备了一系列（2 R，5 S）和（2 S，5 S）-2-羟甲基-5-烷基哌嗪1-5，没有任何消旋作用。描述了将这些化合物用作手性催化剂以将二乙基锌对映异构地加成到醛中。本文报道了在不对称合成中使用哌嗪甲醇的第一个实例。
• Cyclo(Dehydroala-L-Leu), an .ALPHA.-Glucosidase Inhibitor from Penicillium sp. F70614.
  作者：OH SUNG KWON、SANG HO PARK、BONG-SIK YUN、YU RYANG PYUN、CHANG-JIN KIM

  DOI：10.7164/antibiotics.53.954

  日期：——

  A diketopiperazine (1) has been isolated from the culture broth of Penicillium sp. F70614 and its structure has been determined to be cyclo(dehydroala-L-Leu) by various spectroscopic analyses. This compound selectively inhibited yeast α-glucosidase and porcine intestinal α-glucosidase with IC50 values of 35 and 50 μg/ml, respectively. However, it did not show significant inhibitory effects against almond β-glucosidase, Aspergillus α-galactosidase, Escherichia coli β-galactosidase and jack bean α-mannosidase.

  从Penicillium sp. F70614的培养液中分离出一个二酮哌嗪 (1)，经过各种光谱分析确定其结构为环状(脱氢丙氨酸-L-亮氨酸)。该化合物选择性抑制酵母α-葡萄糖苷酶和猪肠α-葡萄糖苷酶，IC50值分别为35和50 μg/ml。然而，它对杏仁β-葡萄糖苷酶、曲霉α-半乳糖苷酶、大肠杆菌β-半乳糖苷酶和菜豆α-甘露糖苷酶未显示显著抑制效果。
• Concise Synthesis of 2,5-Diketopiperazines via Catalytic Hydroxy-Directed Peptide Bond Formations
  作者：Masayoshi Koshizuka、Kaito Shinoda、Kazuishi Makino、Naoyuki Shimada

  DOI：10.1021/acs.joc.3c00195

  日期：2023.6.2

  concise synthesis of this type of DKPs through diboronic acid anhydride-catalyzed hydroxy-directed peptide bond formations. The sequential reactions in this report, which consist of three steps, an intermolecular catalytic condensation reaction in which water is the only byproduct, a simple deprotection of the nitrogen-protecting group, and an intramolecular cyclization, enabled the synthesis of functionalized

  具有羟甲基官能团的 2,5-二酮哌嗪 (DKP) 是许多生物活性分子和功能材料中的必需结构。我们已经建立了一个简单的协议，用于通过二硼酸酐催化的羟基定向肽键形成简明合成此类 DKP。本报告中的连续反应由三个步骤组成，其中水是唯一的副产物的分子间催化缩合反应、氮保护基团的简单脱保护和分子内环化，使功能化 DKPs 的合成成为可能。无需任何中间纯化即可获得优异的产量。该协议的效用已通过合成天然产物、phomamide 和 Cyclo(Deala- l -Leu) 得到证明。
• Cyclic dipeptides exhibit potency for scavenging radicals
  作者：Tadashi Furukawa、Takashi Akutagawa、Hitomi Funatani、Toshikazu Uchida、Yoshihiro Hotta、Masatake Niwa、Yoshiaki Takaya

  DOI：10.1016/j.bmc.2012.01.050

  日期：2012.3

  Twenty kinds of cyclic dipeptides containing L-leucine were synthesized, and their antioxidant activity against (OH)-O-center dot and O-2(center dot-) was investigated. Compounds possessing polar amino acid residues, such as Asp, Cys, Glu, Lys, Pro, Ser, and Trp, exhibited higher antioxidant activity against (OH)-O-center dot than vitamin E. However, only cyclo(L-Cys-L-Leu) scavenged O-2(center dot-). (C) 2012 Elsevier Ltd. All rights reserved.
• Development of a Peptide–Drug Conjugate for Prostate Cancer Therapy
  作者：Wanyi Tai、Ravi S. Shukla、Bin Qin、Benyi Li、Kun Cheng

  DOI：10.1021/mp200007b

  日期：2011.6.6

  TGX-221 is a highly potent phosphoinositide 3-kinase beta (PI3K beta) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-221 to HER2 overexpressing prostate cancer cells. Four TGX-221 derivatives with added hydroxyl groups were synthesized for peptide conjugation. Among them, TGX-D1 exhibited a similar bioactivity to TGX-221, and it was selected for conjugation with a peptide promoiety containing a HER2-targeting ligand and a prostate specific antigen (PSA) substrate linkage. From this selection, the peptide-drug conjugate was proven to be gradually cleaved by PSA to release TGX-D1. Cellular uptake of the peptide-drug conjugate was significantly higher in prostate cancer cells compared to the parent drug. Moreover, both the peptide-drug conjugate and its cleaved products demonstrated comparable activities as the parent drug TGX-D1. Our results suggest that this peptide-drug conjugate may provide a promising chemotherapy for prostate cancer patients.