N-propionyl-L-leucine | 55443-74-8

• 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: N-propionyl-L-leucine
• 英文别名: N-Propionyl-L-leucin；N-ethylcarbonyl-L-leucine；Propionyl-l-leucine；(2S)-4-methyl-2-(propanoylamino)pentanoic acid
• CAS: 55443-74-8
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: QIKGGDCADJHDGD-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-propionyl-L-leucine 在 聚合甲醛 、 水 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 (S)-4-((S)-4-methyl-2-propionamidopentanamido)-5-oxopentanoic acid
  参考文献：
  名称：

  通过研究广泛的人类肠道细菌生物合成途径发现小分子蛋白酶抑制剂

  摘要：

  来自人类微生物群的天然产物可能介导宿主的健康和疾病。但是，发现产生这些代谢产物的生物合成基因簇的发现远远超过了分子本身的鉴定。在这里，我们使用了一种独立于分离的方法来访问来自丰富的肠道共生细菌布鲁米球菌的非核糖体肽合成酶编码基因簇的可能产物。通过将生物信息学与生物合成酶的体外生化特征相结合，我们预测该途径可能会产生N-酰化的二肽醛（瘤胃肽素）。然后，我们使用化学合成方法来获得公认的反刍肽素支架。这些化合物中的几种抑制金黄色葡萄球菌内蛋白酶GluC（SspA / V8蛋白酶）。这种蛋白酶的同系物存在于肠道共生和机会病原体以及人类肠道的基因组中。总的来说，这项工作揭示了不依赖分离的方法可快速获取生物活性化合物的实用性，并突出了肠道微生物天然产物在靶向肠道微生物蛋白酶方面的潜在作用。

  DOI：

  10.1016/j.tet.2018.03.043
• 作为产物：
  描述：

  N-ethylcarbonyl-L-leucine ethyl ester 在 sodium hydroxide 、 盐酸 、 水 作用下， 以 乙醇 、 水 为溶剂， 反应 168.0h， 以96%的产率得到N-propionyl-L-leucine
  参考文献：
  名称：

  The urea-dipeptides show stronger H-bonding propensity to nucleate β-sheetlike assembly than natural sequence

  摘要：

  In this article, we report the distinct solution behavior of a set of urea-dipeptides to that of natural sequence. The urea-dipeptides adopt beta-folding conformations and form into beta-sheetlike assembly in chloroform. Most surprisedly, the urea-dipeptides tend to form interpeptide H-bonding interactions even at a concentration of as low as 0 1 mM, while the natural sequence shows H-bonding propensity at a concentration of about 7 mM, indicating that the urea-dipeptides Show Much stronger H-bonding propensity to nucleate formation of beta-sheetlike assembly than the natural sequence CD spectra reveal that the investigated urea-dipeptides have two negative CD bands, respectively, around 217 nm and 224 nm, supporting the beta-folding conformations and in turn formation of beta-sheetlike assembly. The beta-sheetlike assembly is also confirmed by the XRD reflections, which give two typical d-spacings of 12 7 and 4 8 angstrom, respectively, corresponding to stacking periodicity of the beta-sheets and the spacing between peptide backbones running orthogonal to the beta-sheet axis. (C) 2009 Elsevier Ltd All rights reserved

  DOI：

  10.1016/j.tet.2009.07.048

文献信息

• Substituted Morphinans and the Use Thereof
  申请人：Purdue Pharma L.P.

  公开号：US20140187573A1

  公开（公告）日：2014-07-03

  The application is directed to compounds of Formula I: and pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2 , R 3 , R 4a , and R 4b are defined as set forth in the specification. The invention is also directed to use of compounds of Formula I to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the present invention are especially useful for treating pain.

  本申请涉及式I化合物： 及其医药可接受的盐和溶剂化物，其中R1、R2、R3、R4a和R4b的定义如说明书中所述。本发明还涉及使用式I化合物来治疗对一或多个阿片受体调节有反应的疾病，或作为合成中间体。本发明中的某些化合物特别适用于治疗疼痛。
• Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics
  作者：Zheliang Yuan、Hua Yang、Noeen Malik、Milena Čolović、David S. Weber、Darryl Wilson、François Bénard、Rainer E. Martin、Jeffrey J. Warren、Paul Schaffer、Robert Britton

  DOI：10.1021/acscatal.9b02220

  日期：2019.9.6

  The site-selective fluorination of unactivated C(sp3)-H bonds provides unique opportunities to rapidly alter drug properties or generate radiotracers for positron emission tomography (PET) imaging. Toward this goal, photoactivated decatungstate (DT) is capable of generating carbon radicals through hydrogen atom transfer that subsequently undergo fluorination by reaction with N-fluorobenzenesulfonimide

  未激活的C（sp 3）-H键的位点选择性氟化为快速改变药物性质或生成正电子发射断层扫描（PET）成像的放射性示踪剂提供了独特的机会。朝着这个目标迈进，光活化的去氢钨酸盐（DT）能够通过氢原子转移产生碳自由基，随后通过与N-氟苯磺酰亚胺（NFSI）或[ 18 F] NFSI反应进行氟化。此过程使C（sp 3）-H氟化是多种脂族化合物的反应，尽管反应速率可能变化很大，并限制了在放射性示踪剂合成中的应用。在这里，我们证明脂族分子中的阳离子铵功能促进了与DT的前体复合物的形成，从而显着提高了C–H提取的速率。这种加快速率的静电效应的普遍用途在包括氨基酸，杂环和假肽在内的30多种含铵分子上得到了证明。此外，在快速生产18 F标记的前列腺特异性膜抗原（PSMA）结合配体[ 18 F] Glu-U-FHLeu时，这种效果得到了突出体现。
• C. elegans as a model for inter-individual variation in metabolism
  作者：Bennett W. Fox、Olga Ponomarova、Yong-Uk Lee、Gaotian Zhang、Gabrielle E. Giese、Melissa Walker、Nicole M. Roberto、Huimin Na、Pedro R. Rodrigues、Brian J. Curtis、Aiden R. Kolodziej、Timothy A. Crombie、Stefan Zdraljevic、L. Safak Yilmaz、Erik C. Andersen、Frank C. Schroeder、Albertha J. M. Walhout

  DOI：10.1038/s41586-022-04951-3

  日期：2022.7.21

  Individuals can exhibit differences in metabolism that are caused by the interplay of genetic background, nutritional input, microbiota and other environmental factors1–4. It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans, owing to differences in diet and lifestyle, among others. Here we use the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known metabolites and those that have not to our knowledge been previously described. The latter metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs), which are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin-B12-dependent propionate breakdown pathway is perturbed5. We show that increased accumulation of 3HP-AAs is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that the production of 3HP-AAs represents a ‘shunt-within-a-shunt’ pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a step towards the development of metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity that is found in entire species. Using differences among strains as a model for inter-individual variation, this paper identifies a conserved metabolicadaptation in C. elegans that compensates for genetic variation.

  个体之间的新陈代谢差异可能是由遗传背景、营养摄入、微生物群和其他环境因素相互作用引起的1-4。由于饮食和生活方式等方面的差异，很难将新陈代谢的差异与基因组变异联系起来，并从中得出人类潜在的分子机制。在这里，我们以线虫秀丽隐杆线虫（Caenorhabditis elegans）为模型，研究个体之间的新陈代谢差异。通过比较三个野生菌株和常用的N2实验室菌株，我们发现已知代谢物和那些以前未知的代谢物的丰度存在差异。后者包括3-羟基丙酸盐（3HP）和几种氨基酸（3HP-AAs）之间的结合物，其中一种野生菌株中的含量要高得多。3HP是丙酸盐分流途径的中间产物，当通过典型的、维生素B12依赖的丙酸盐分解途径的通量受到干扰时，丙酸盐分流途径就会被激活5。我们表明，3HP-AAs的积累增加是由HPHD-1的遗传变异引起的，而3HP是HPHD-1的底物。我们的结果表明，3HP-AAs的产生代表了一种“分流中的分流”途径，以适应hphd-1中功能降低的等位基因。这项研究为开发代谢网络模型迈出了一步，该模型可以捕捉个体特定的代谢差异，并更准确地反映整个物种的多样性。本文以菌株之间的差异为个体差异模型，确定了秀丽隐杆线
• Enlargement of mucocutaneous or cutaneous organs and sites with topical compositions
  申请人：Yu J. Ruey

  公开号：US20050171194A1

  公开（公告）日：2005-08-04

  Compositions comprising a hydroxycarboxylic acid, N-acyl-aldosamine, N-acylamino acid or related compound on topical application are beneficial to plump and pout lips, enhance and firm eyelids, enlarge and augment breasts, elongate and expand penis. Because of antioxidant property, certain hydroxycarboxylic acids, N-acyl-aldosamines, N-acylamino acids and related compounds also are useful for topical administration to prevent occurrence of breast cancer or other forms of tumors and cancers.

  由羟基羧酸、N-酰基-醛糖胺、N-酰基氨基酸或相关化合物组成的组合物在局部使用时有利于丰满嘴唇、增强和紧实眼睑、增大和隆起乳房、拉长和扩张阴茎。由于具有抗氧化性，某些羟基羧酸、N-酰基醛胺和 N-酰基氨基酸及相关化合物还可用于局部用药，以预防乳腺癌或其他形式的肿瘤和癌症的发生。
• Compositions comprising N-propanoyl derivatives of amino acids, aminocarbohydrates and derivatives thereof
  申请人：Yu J. Ruey

  公开号：US20060211754A1

  公开（公告）日：2006-09-21

  The embodiments relate to compositions comprising therapeutically effective amounts of at least one N-propanoyl derivative of amino acids, aminocarbohydrates, and derivatives thereof. The compositions are useful the prevention and treatment of symptoms or syndromes associated with nervous, vascular, musculoskeletal, or cutaneous systems. The compositions may be topically or systemically administered to a subject in need thereof.

  本发明的实施方案涉及包含治疗有效量的至少一种氨基酸、氨基碳水化合物及其衍生物的 N-丙酰基衍生物的组合物。这些组合物有助于预防和治疗与神经、血管、肌肉骨骼或皮肤系统有关的症状或综合征。这些组合物可局部或全身施用给需要的受试者。