benzyl 1,2,3,4-tetrahydro-5-methyl-2,4-dioxopyrimidine-1-acetate | 380637-97-8

• 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: benzyl 1,2,3,4-tetrahydro-5-methyl-2,4-dioxopyrimidine-1-acetate
• 英文别名: benzyl 2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetate；benzyl (5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetate；benzyl 2-(5-methyl-2,4-dioxopyrimidin-1-yl)acetate
• CAS: 380637-97-8
• 化学式: C₁₄H₁₄N₂O₄
• 分子量: 274.276
• InChiKey: PCHQLPVUECDATJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 1,2,3,4-tetrahydro-5-methyl-2,4-dioxopyrimidine-1-acetate 在 palladium on activated charcoal 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.67h， 生成 N-[2-(7,8-dimethyl-2,4-dioxo-3-pentyl-3,4-dihydro-2H-benzo[g]pteridin-10-yl)-ethyl]-2-(6-methyl-3,5-dioxo-8,8-diphenyl-7-oxa-2,4-diaza-bicyclo[4.2.0]oct-2-yl)-acetamide
  参考文献：
  名称：

  Model compounds for (6–4) photolyases: a comparative flavin induced cleavage study of oxetanes and thietanes

  摘要：

  硫环化合物曾被用作修复诱变性 (6–4) 损伤过程中形成的不稳定氧四环中间体的模仿物。研究发现，硫环衍生物未被修复，这引发了一个问题：与氧四环相比，硫环在单电子供体作用下的裂解效果如何。我们为 (6–4) 光裂解酶催化的修复过程制备了两个含黄素的氧四环和硫环模型化合物，并展示了二者都能被还原和去质子化的黄素高效裂解。因此，硫环是优秀的模型。它们缺乏修复的原因可归因于缺乏结合。

  DOI：

  10.1039/b503205a
• 作为产物：
  描述：

  苯甲醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 benzyl 1,2,3,4-tetrahydro-5-methyl-2,4-dioxopyrimidine-1-acetate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x

文献信息

• Selective product amplification of thymine photodimer by recognition-directed supramolecular assistance
  作者：W. G. Skene、Volker Berl、H?l?ne Risler、Richard Khoury、Jean-Marie Lehn

  DOI：10.1039/b605658j

  日期：——

  Two symmetric ditopic supramolecular templates (1 and 2) each presenting two hydrogen bonding recognition subunits were synthesized. Each such subunit comprises the same donor and acceptor pattern, capable of binding a substrate molecule with complementary hydrogen bonding groups to form a supramolecular complex. Substrate molecules, such as thymine or uracil derivatives, yield 2 : 1 complexes with the acceptors involving two hydrogen bonds to each subunit with ideal orientation for subsequent [2 + 2] dimerization upon photoirradiation. Selective syn photoproduct formation and concomitant suppression of the trans isomer are favored by orientation of the two guest nucleobases within the template cleft. Complementary donor and acceptor hydrogen bonding induced positioning of the two substrates and steric hindrance within the template clefts are responsible for the selective product formation.

  合成了两种对称的双位点超分子模板（1和2），每种模板都呈现出两个氢键识别子单元。每个这样的子单元包含相同的供体和受体模式，能够与具有互补氢键基团的底物分子结合，形成超分子复合物。例如胸腺嘧啶或尿嘧啶衍生物等底物分子，与受体形成2 : 1的复合物，每个子单元通过两个氢键在理想方向上结合，便于光照射后发生[2 + 2]二聚化反应。客体核碱基在模板裂隙内的定向排列有利于选择性syn光产物形成，同时抑制trans异构体。互补的供体和受体氢键诱导的底物定位以及模板裂隙内的空间位阻是选择性产物形成的原因。
• A Comparative Repair Study of Thymine- and Uracil-Photodimers with Model Compounds and a Photolyase Repair Enzyme
  作者：Jens Butenandt、Robert Epple、Ernst-Udo Wallenborn、André P. M. Eker、Volker Gramlich、Thomas Carell

  DOI：10.1002/(sici)1521-3765(20000103)6:1<62::aid-chem62>3.0.co;2-7

  日期：2000.1.3

  conditions revealed, in contrast to all previous findings, faster repair of the sterically less encumbered uracil dimer. Stereoelectronic effects are offered as a possible explanation. Ab initio calculations and X-ray crystal structure data reveal a different cyclobutane ring pucker of the uracil dimer, which leads to a better overlap of the pi*-C(4)-O(4)-orbital with the sigma*-C(5)-C(5')-orbital. Enzymatic

  具有顺式-syn结构的环丁烷尿苷和胸苷二聚体是DNA损伤，可通过DNA光解酶在许多物种中得到有效修复。修复反应的关键步骤是光驱使电子从还原的FAD辅因子（FADH）转移至二聚体病变，该二聚体病变自发分裂成单体。用紫外线破坏的DNA进行的修复研究表明，各种二聚体损伤的比率明显不同。特别地，在胸苷环丁烷二聚体部分上几乎黯然失色的甲基对分裂速率的影响是未知的。为了研究胸腺嘧啶和尿嘧啶环丁烷光二聚体在蛋白质环境之外的裂解脆弱性，制备了两种模型化合物，它们包含胸腺嘧啶或尿嘧啶二聚体和共价连接的黄素，并进行了比较研究。与以前的所有发现相比，在内部竞争条件下进行的裂解研究表明，在空间上受累的尿嘧啶二聚体的修复速度更快。提供了立体电子效应作为可能的解释。从头算和X射线晶体结构数据揭示了尿嘧啶二聚体的不同环丁烷环褶皱，这导致pi * -C（4）-O（4）-轨道与sigma * -C（ 5）-C（5'）-轨道
• Model studies of the (6–4) photoproduct photoreactivation: efficient photosensitized splitting of thymine oxetane units by covalently linked tryptophan in high polarity solvents
  作者：Qin-Hua Song、Hong-Bo Wang、Wen-Jian Tang、Qing-Xiang Guo、Shu-Qin Yu

  DOI：10.1039/b514921e

  日期：——

  Three covalently linked tryptophan-thymine oxetane compounds used as a model of the (6-4) photolyase-substrate complex have been prepared. Under 290 nm light, efficient splitting of the thymine oxetane with aromatic carbonyl compounds gives the thymine monomer and the corresponding carbonyl compounds by the covalently linked tryptophan via an intramolecular electron transfer, and exhibits a strong

  制备了三种共价连接的色氨酸-胸腺嘧啶氧杂环丁烷化合物，用作（6-4）光裂解酶-底物复合物的模型。在290 nm的光下，胸腺嘧啶氧杂环丁烷与芳族羰基化合物的有效拆分通过分子内电子转移通过共价键合的色氨酸产生了胸腺嘧啶单体和相应的羰基化合物，并且表现出强烈的溶剂依赖性：量子产率（Phi）为约。在二恶烷中为0.1，在水中为0.3。电子从激发的色氨酸残基转移到氧杂环丁烷单元是色氨酸残基荧光猝灭的起因，并且在强极性溶剂中更有效。色氨酸+-氧杂环丁烷-物种内氧杂环丁烷自由基阴离子的拆分效率也取决于溶剂，范围大约为。在二恶烷中为0.2，在水中接近0.35。因此，电荷分离的物质中的逆电子转移反应在水中将被抑制，但是仍然是导致色氨酸-氧杂环丁烷体系中低拆分效率的主要因素。与色氨酸-氧杂环丁烷体系相反，快速的非辐射过程是黄素-氧杂环丁烷体系效率低下的主要原因。因此，激发的FADH-的非辐射过程，而不是电子转移
• Investigation of the Pathways of Excess Electron Transfer in DNA with Flavin-Donor and Oxetane-Acceptor Modified DNA Hairpins
  作者：Sascha Breeger、Martin von Meltzer、Ulrich Hennecke、Thomas Carell

  DOI：10.1002/chem.200600074

  日期：2006.8.25

  during the repair of (6-4) DNA lesions by special repair enzymes (6-4 DNA photolyases). These enzymes use a reduced and deprotonated flavin to cleave the oxetane by single electron donation. Herein we report synthesis of DNA hairpin model compounds containing a flavin as the hairpin head and two different oxetanes in the stem structure of the hairpin. The data show that the electron moves through the duplex

  氧杂环丁烷是一种潜在的中间体，在特殊的修复酶（6-4 DNA光解酶）修复（6-4）DNA损伤时会通过酶促形成。这些酶使用还原的和去质子化的黄素通过单电子给体切割氧杂环丁烷。在本文中，我们报道了DNA发夹模型化合物的合成，该化合物包含黄素作为发夹头，并且在发夹的茎结构中包含两种不同的氧杂环丁烷。数据表明，即使在17 A的距离上，电子也能通过双链体移动。用N2O捕获移动的电子的尝试并未显示出裂解效率的降低，这表明电子移动通过双链体而不是通过溶液。电子转移取决于序列。在富含GC的DNA发夹中，效率降低了2倍。
• SPECIFIC SYNTHETIC CHIMERIC XENONUCLEIC ACID GUIDE RNA; s(XNA-gRNA) FOR ENHANCING CRISPR MEDIATED GENOME EDITING EFFICIENCY
  申请人：Powell Michael J

  公开号：US20190330621A1

  公开（公告）日：2019-10-31

  The invention provides xenonucleic acids and synthetic chimeric xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing crispr mediated genome editing efficiency. The invention also provides methods and compositions for inducing CRISPR/Cas-based gene editing/regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using single guide RNAs (sgRNAs) that have been chemically modified with xeno nucleic acids which enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a sgRNA that has been chemically modified with xeno nucleic acids to correct a mutation in a target gene associated with the genetic disease.

  该发明提供了xenonucleic acids和合成嵌合xenonucleic acid guide RNA；s(XNA-gRNA)，用于增强criSPr介导的基因组编辑效率。该发明还提供了诱导CRISPR/Cas基因编辑/调控（例如基因组编辑或基因表达）靶向核酸（例如靶向DNA或靶向RNA）在细胞中的方法和组合物。这些方法包括使用已经经过化学修饰的xeno核酸的单导RNA（sgRNAs），这些核酸增强了原代细胞中靶向核酸的基因调控，用于体外治疗或用于体内治疗中的受体细胞。此外，本文提供了通过向受体注射已经经过化学修饰的xeno核酸的足够数量的sgRNA来预防或治疗受体的遗传疾病的方法，以纠正与该遗传疾病相关的靶基因的突变。