4-[[(2R)-2,4-二羟基-3,3-二甲基-1-氧代丁基]氨基]-丁酸 | 18679-90-8

• 物质功能分类: 分析化学 - 标准品 - 分析标准品
• 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
• 中文名称: 4-[[(2R)-2,4-二羟基-3,3-二甲基-1-氧代丁基]氨基]-丁酸
• 中文别名: 高泛酸；右泛醇杂质I
• 英文名称: hopantenic acid
• 英文别名: D-Homopantothenic acid；4-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]butanoic acid
• CAS: 18679-90-8
• 化学式: C₁₀H₁₉NO₅
• 分子量: 233.265
• InChiKey: SBBDHANTMHIRGW-QMMMGPOBSA-N

物化性质

• 熔点：
  62-64 °C
• 比旋光度：
  D20 +23.8°
• 沸点：
  556.0±50.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924199090
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319
• 储存条件：
  -20°C，干燥且密封保存。

制备方法与用途

Hopan抑制磷酸泛酰半胱氨酸合成酶的活性。

反应信息

• 作为反应物：
  描述：

  3,4,5-三甲氧基苄胺 、 4-[[(2R)-2,4-二羟基-3,3-二甲基-1-氧代丁基]氨基]-丁酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以60%的产率得到2,4-dihydroxy-3,3-dimethyl-N-[2-(3,4,5-trimethoxybenzylcarbamoyl)ethyl]-butyramide
  参考文献：
  名称：

  Structure–activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors

  摘要：

  A set of novel pantothenamide-type analogues of the known Staphylococcus aureus pantothenate kinase (SaPanK) inhibitors, N-pentyl, and N-heptylpantothenamide, was synthesized in three series. The first series of analogues (1-3) were designed as molecular probes of the PanK binding site to elucidate important structure-activity relationships (SAR). The second series of analogues (4-16) were designed using Structural information obtained from the Escherichia coli PanK (EcPanK) Structure by targeting the pantothenate binding site and the adjacent phenylalanine-lined lipophilic pocket. Insight into the antimicrobial effect of N-pen- tylpantothenamide (N5-Pan) through its Conversion to the antimetabolite ethyldethia-CoA and further incorporation into all inactive acyl carrier protein analogue drove the development of the third series of analogues (17-25) to enhance this effect using substrate-like substitutions. Each of the analogues was screened for enzyme inhibition activity against a panel of pantothenate kinases consisting of EcPanK, Aspergillus nidulans (AnPanK), SaPanK, and the murine isoform (MmPanK1 alpha). Series 1 demonstrated only modest inhibitory activity, but did reveal some important SAR findings including stereospecific binding. Series 2 demonstrated a much higher inhibition rate for the entire series and significant inhibition was seen with analogues containing alkyl substituents. Series 3 demonstrated the most preferential inhibition profile, with the highest inhibitory activity against the SaPanK greater selectivity. The overall activity data from these analogues Suggest a complex and non-enzynie specific SAR for pantotheriamide substrate/inhibitors of the different PanK enzymes. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.021
• 作为产物：
  描述：

  D-(-)-泛酰内酯 在 二乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.75h， 生成 4-[[(2R)-2,4-二羟基-3,3-二甲基-1-氧代丁基]氨基]-丁酸
  参考文献：
  名称：

  探索三种细菌泛酸激酶的配体偏好

  摘要：

  泛酸激酶（PanK）催化泛酸向4'-磷酸泛酸的转化，这是辅酶A生物合成的第一步。尽管已经报道了多种泛酸抗代谢物和PanK抑制剂可用于细菌I型和II型PanK，但只有少数弱抑制剂可用于细菌III型PanK酶。在这里，使用方便的合成方法合成了一系列泛酸类似物。将该化合物用作小型有机探针，以比较三种不同类型细菌PanK的配体偏好。总体而言，每种PanK类型都鉴定了几种新的抑制剂和底物。

  DOI：

  10.1016/j.bmc.2018.10.042

文献信息

• Development of a method for the parallel synthesis and purification of N-substituted pantothenamides, known inhibitors of coenzyme A biosynthesis and utilization
  作者：Marianne van Wyk、Erick Strauss

  DOI：10.1039/b811086g

  日期：——

  analogues which have been shown to act as inhibitors of coenzyme A biosynthesis and utilization, especially by blocking fatty acid metabolism through formation of inactive acyl carrier proteins. To fully explore the chemical diversity and inhibitory potential of these analogues we have developed a simple method for the parallel synthesis and purification of any number of pantothenamides from a single precursor

  N-取代的泛酰胺是一类泛酸类似物，已被证明可作为辅酶A生物合成和利用的抑制剂，特别是通过形成无活性的酰基载体蛋白来阻止脂肪酸代谢。为了全面探索这些类似物的化学多样性和抑制潜力，我们开发了一种简单的方法，用于从单个前体中并行合成和纯化任意数量的泛酰胺，随后评估了这些化合物的小文库作为细菌生长的抑制剂，以证明该方法的潜力和实用性。
• Chemical Proteomic Profiling of Protein 4′‐Phosphopantetheinylation in Mammalian Cells
  作者：Nan Chen、Yuan Liu、Yuanpei Li、Chu Wang

  DOI：10.1002/anie.202004105

  日期：2020.9.7

  ted proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4′‐phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4′‐phosphopantetheinylation site in the protein of mitochondrial

  在原核生物和真核生物中，蛋白质4'-磷酸泛锡基化是必不可少的翻译后修饰（PTM）。到目前为止，在哺乳动物细胞中仅发现了该特定PTM的五个蛋白质底物。已知这些蛋白质具有重要功能，包括脂肪酸生物合成和叶酸代谢以及β-丙氨酸激活。为了探索哺乳动物蛋白质组中现有的和新的4'-磷酸泛素化底物，我们设计并合成了一系列新的泛素类似物探针，可对HepG2细胞中的4'-磷酸泛素化蛋白进行有效的代谢标记。结合定量化学蛋白质组学平台，我们以高可信度丰富并鉴定了所有目前已知的所有4'-磷酸泛素化蛋白，并明确确定其确切的修饰位点。更令人鼓舞的是，我们使用靶向化学蛋白质组学在线粒体脱氢酶/还原酶SDR家族成员2（DHRS2）的蛋白质中发现了一个潜在的4'-磷酸泛锡基化位点。
• AMIDES OF CREATNE, METHOD OF THEIR PREPARATION, AND REMEDY POSSESSING A NEUROPROTECTIVE ACTIVITY
  申请人：Burov Sergej Vladimirovich

  公开号：US20110269986A1

  公开（公告）日：2011-11-03

  The invention relates to pharmaceutical chemistry notably to new biologically active substances (BAS) and their properties. In particular, the invention relates to Creatine derivatives having a general formula: NH═C(NH 2 )—N(CH 3 )—CH 2 —CO—NH—R*X, wherein R—amino acid residue of aliphatic, aromatic or heteroaromatic L-amino acid or its derivative representing a salts of amino acid, amino acid esters, amino acid amides or peptides; X—lower organic or mineral acid or water. New substances are prepared by interaction of aforesaid amides of sarcosine having a general formula of HN(CH 3 )—CH 2 —CO—NH—R*X, wherein: R is amino acid residue or substituted amino acid residue; X is low-molecular-weight organic acid or mineral acid or water, with a guanidinylating agents with the in organic solvents at temperature not exceeding 50° C. New chemical compounds can be used as a remedy possessing a neuroprotective activity.

  该发明涉及制药化学，特别是新的生物活性物质（BAS）及其性质。具体而言，该发明涉及具有一般式的肌酸衍生物：NH═C(NH 2 )—N(CH 3 )—CH 2 —CO—NH—R*X，其中R为脂肪族、芳香族或杂环芳基L-氨基酸或其衍生物的氨基酸残基，代表氨基酸盐、氨基酸酯、氨基酸酰胺或肽；X为低级有机酸或矿物酸或水。新物质通过上述具有一般式的肌氨酸酰胺的相互作用制备而成，其中：R为氨基酸残基或取代氨基酸残基；X为低分子量有机酸或矿物酸或水，与有机溶剂中的胍基化剂在不超过50°C的温度下反应。新的化合物可用作具有神经保护活性的药物。
• Diagnostic/therapeutic agents
  申请人：Klaveness Jo

  公开号：US20050002865A1

  公开（公告）日：2005-01-06

  Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

  可定位的诊断和/或治疗活性剂，例如超声对比剂，包括悬浮在水载体液中的报告物，该报告物包含含气体或生成气体的材料，该剂能够与目标形成至少两种结合对。
• NEUROTROPIC AGENT AND PROCESS FOR PRODUCING IT
  申请人：NAUCHNO-PROIZVODSTVENNOE OBIEDINENIE "VITAMINY"

  公开号：EP0717991A1

  公开（公告）日：1996-06-26

  A new chemical compound, ketopantoic aminobutyrate of formula I: and its salts. The compound is obtained by interaction of ketopantolactone and a salt of γ-aminobutyric acid. It was shown that the new compound exhibits sedative, anti-amnesic and antihypoxic properties.

  一种新化合物，即式 I 的酮泛酸氨基丁酸盐： 及其盐类。 该化合物由酮泛酸内酯和 γ-氨基丁酸盐相互作用而得。 研究表明，这种新化合物具有镇静、抗失水和抗缺氧的特性。