(3aS,4S,6aR)-4-(4-aminobut-1-yl)hexahydro-1H-thieno[3,4-d]imidazolidin-2-one hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并咪唑类化合物
• 英文名称: (3aS,4S,6aR)-4-(4-aminobut-1-yl)hexahydro-1H-thieno[3,4-d]imidazolidin-2-one hydrochloride
• 英文别名: norbiotinamine hydrochloride；(3aS,4S,6aR)-4-(4-aminobutyl)tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one hydrochloride；norbiotinamine monohydrochloride；(3aS)-4t-(4-amino-butyl)-(3ar,6ac)-tetrahydro-thieno[3,4-d]imidazol-2-one; hydrochloride；(3aS)-4t-(4-Amino-butyl)-(3ar,6ac)-tetrahydro-thieno[3,4-d]imidazol-2-on; Hydrochlorid；(3aS,4S,6aR)-4-(4-aminobutyl)-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-2-one;hydrochloride
• 化学式: C₉H₁₇N₃OS*ClH
• 分子量: 251.78
• InChiKey: BPNHGUOHVHHZMG-WQYNNSOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  92.4
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3aS,4S,6aR)-4-(4-aminobut-1-yl)hexahydro-1H-thieno[3,4-d]imidazolidin-2-one hydrochloride 在 1H-咪唑-1-磺酰叠氮盐酸盐 、 copper(ll) sulfate pentahydrate 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以74%的产率得到(3aS,4S,6aR)-4-(4-azidobut-1-yl)hexahydro-1H-thieno[3,4-d]imidazolidin-2-one
  参考文献：
  名称：

  Chloromethyl-triazole: a new motif for site-selective pseudo-acylation of proteins

  摘要：

  氯甲基三唑被证明是半胱氨酸选择性烷基化试剂，用于蛋白质和肽基底物的“近似天然”的翻译后修饰。

  DOI：

  10.1039/c6cc06801d
• 作为产物：
  描述：

  N-Boc-norbiotinamine 在 乙酰氯 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 4.0h， 以95%的产率得到(3aS,4S,6aR)-4-(4-aminobut-1-yl)hexahydro-1H-thieno[3,4-d]imidazolidin-2-one hydrochloride
  参考文献：
  名称：

  Chloromethyl-triazole: a new motif for site-selective pseudo-acylation of proteins

  摘要：

  氯甲基三唑被证明是半胱氨酸选择性烷基化试剂，用于蛋白质和肽基底物的“近似天然”的翻译后修饰。

  DOI：

  10.1039/c6cc06801d

文献信息

• [EN] NOVEL ANTIBIOTIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTIBIOTIQUES
  申请人：UNIV ADELAIDE

  公开号：WO2020087122A1

  公开（公告）日：2020-05-07

  Novel antimicrobial inhibitors of Biotin Protein Ligase (BPL), which incorporate biotin, are described. The inhibitors have a structure that inhibit the essential metabolic enzyme BPL of pathogens and have been shown to be stable in whole blood and effective at reducing BPL activity in acceptable concentrations. The described compounds have shown to be effective against, for example, Staphylococcus aureus and compare favourably against erythromycin

  描述了一种新型抗微生物生物素蛋白连接酶（BPL）抑制剂，其中包含生物素。这些抑制剂具有一种结构，可以抑制病原体的关键代谢酶BPL，并且已经证明在全血中稳定，并且在可接受的浓度下能有效降低BPL活性。所描述的化合物已被证明对金黄色葡萄球菌等病原体有效，并且与红霉素相比具有较好的效果。
• Biotin Analogues with Antibacterial Activity Are Potent Inhibitors of Biotin Protein Ligase
  作者：Tatiana P. Soares da Costa、William Tieu、Min Y. Yap、Ondrej Zvarec、Jan M. Bell、John D. Turnidge、John C. Wallace、Grant W. Booker、Matthew C. J. Wilce、Andrew D. Abell、Steven W. Polyak

  DOI：10.1021/ml300106p

  日期：2012.6.14

  bacteria, such as clinically important Staphylococcus aureus. The essential multifunctional enzyme, biotin protein ligase (BPL), is one potential drug target for new antibiotics. We report the synthesis and characterization of a series of biotin analogues with activity against BPLs from S. aureus, Escherichia coli, and Homo sapiens. Two potent inhibitors with K i < 100 nM were identified with antibacterial

  迫切需要开发新的抗生素来抵抗耐药细菌的繁殖，例如临床上重要的金黄色葡萄球菌。基本的多功能酶生物素蛋白连接酶（BPL）是新抗生素的潜在药物靶标之一。我们报告了一系列生物素类似物的合成和表征，这些生物素类似物具有针对来自金黄色葡萄球菌，大肠杆菌和智人的BPL的活性。鉴定出K i <100 nM的两种有效抑制剂对一组金黄色葡萄球菌临床分离株具有抗菌活性（MIC 2-16杯/ mL）。鉴定并表征了具有高配体效率和同工酶之间选择性> 20倍的化合物。抗菌作用方式显示为通过抑制BPL。BPL和抑制剂之间的双分子相互作用是通过表面等离振子共振研究和X射线晶体学确定的。这些发现为具有更高效力和选择性的第二代抑制剂和抗生素铺平了道路。
• An Artificial Metalloenzyme Based on a Copper Heteroscorpionate Enables sp³ C–H Functionalization via Intramolecular Carbene Insertion
  作者：Corentin Rumo、Alina Stein、Juliane Klehr、Ryo Tachibana、Alessandro Prescimone、Daniel Häussinger、Thomas R. Ward

  DOI：10.1021/jacs.2c03311

  日期：2022.7.6

  selective functionalization of sp3 C–H bonds is a versatile tool for the diversification of organic compounds. Combining attractive features of homogeneous and enzymatic catalysts, artificial metalloenzymes offer an ideal means to selectively modify these inert motifs. Herein, we report on a copper(I) heteroscorpionate complex embedded within streptavidin that catalyzes the intramolecular insertion of a

  sp 3 C-H键的选择性功能化是有机化合物多样化的通用工具。结合均相和酶催化剂的有吸引力的特征，人造金属酶提供了一种理想的方法来选择性地修饰这些惰性基序。在此，我们报道了嵌入链霉抗生物素蛋白中的铜 (I) 异蝎形酸盐复合物，该复合物催化卡宾分子内插入 sp 3C-H 键。通过量子力学/分子力学模拟确定了人工金属酶遗传优化的目标残基。双饱和诱变对单个氨基酸对人工金属酶的活性和选择性的贡献产生了详细的了解。第三个位置的诱变提供了一组人工金属酶，可催化β-和γ-内酰胺的对映选择性和区域选择性形成，具有高周转率和有希望的对映选择性。
• Enantioselective Hydroxylation of Benzylic C(sp³)–H Bonds by an Artificial Iron Hydroxylase Based on the Biotin–Streptavidin Technology
  作者：Joan Serrano-Plana、Corentin Rumo、Johannes G. Rebelein、Ryan L. Peterson、Maxime Barnet、Thomas R. Ward

  DOI：10.1021/jacs.0c02788

  日期：2020.6.17

  The selective hydroxylation of C-H bonds is of great interest to the synthetic community. Both homogeneous catalysts and enzymes offer complementary means to tackle this challenge. Herein, we show that biotinylated Fe(TAML)-complexes (TAML = Tetra Amido Macrocyclic Ligand) can be used as cofactors for incorporation into streptavidin to assemble artificial hydroxylases. Chemo-genetic optimization of both cofactor and streptavidin allowed optimizing the performance of the hydroxylase. Using H2O2 as oxidant, up to similar to 300 turnovers for the oxidation of benzylic C-H bonds were obtained. Upgrading the ee was achieved by kinetic resolution of the resulting benzylic alcohol to afford up to >98% ee for (R)-tetralol. X-ray analysis of artificial hydroxylases highlights critical details of the second coordination sphere around the Fe(TAML) cofactor.
• Hofmann et al., Journal of Biological Chemistry, 1942, vol. 144, p. 513,516
  作者：Hofmann et al.

  DOI：——

  日期：——