Conformation-guided analogue design identifies potential antimalarial compounds through inhibition of mitochondrial respiration
文献信息
Erik M. Larsen, Chia-Fu Chang, Tomoyo Sakata-Kato, Joseph W. Arico, Vince M. Lombardo, Dyann F. Wirth, Richard E. Taylor
The synthesis of a 2-methyl-substituted analogue of the natural product, neopeltolide, is reported in an effort to analyze the importance of molecular conformation and ligand–target interactions in relation to biological activity. The methyl substitution was incorporated via highly diastereoselective ester enolate alkylation of a late-stage intermediate. Coupling of the oxazole sidechain provided 2-methyl-neopeltolide and synthetic neopeltolide via total synthesis. The substitution was shown to maintain the conformational preferences of its biologically active parent compound through computer modeling and NMR studies. Both compounds were shown to be potential antimalarial compounds through the inhibition of mitochondrial respiration in P. falciparum parasites.
相关文献
Efficient syntheses and anti-cancer activity of xenortides A–D including ent/epi-stereoisomers
N. Esmati, A. R. Maddirala, N. Hussein, H. Amawi, A. K. Tiwari, P. R. Andreana
DOI: 10.1039/C8OB00452H
Highly chemoselective hydrogenation of cyclic imides to ω-hydroxylactams or ω-hydroxyamides catalyzed by iridium catalysts
Jiang Wang, Xumu Zhang, Runtong Zhang, Baode Ma
DOI: 10.1039/D1QO01100F
C–H alkylation reactions of indoles mediated by Pd(ii) and norbornene: applications and recent developments
Marcus Wegmann, Michael Henkel, Thorsten Bach
DOI: 10.1039/C8OB01025K
Inexpensive NaX (X = I, Br, Cl) as a halogen donor in the practical Ag/Cu-mediated decarboxylative halogenation of aryl carboxylic acids under aerobic conditions
Ligao Jiang, Qianming Zuo, Zhaojie Li, Yanzhu Liu, Zhenhong Wei, Hu Cai
DOI: 10.1039/C8OB01095A
Nα-Amino acid containing privileged structures: design, synthesis and use in solid-phase peptide synthesis
Eva Schütznerová, Adam Přibylka
DOI: 10.1039/C8OB01485J
Synthesis of 6-SF5-indazoles and an SF5-analog of gamendazole
Oleksandr S. Kanishchev, William R. Dolbier, Jr.
DOI: 10.1039/C8OB01460D
Ni-Catalyzed direct iminoalkynylation of unactivated olefins with terminal alkynes: facile access to alkyne-labelled pyrrolines
Xingjie Zhang, Di Qi, Chenchen Jiao, Zhiguo Zhang, Xiaopan Liu, Guisheng Zhang
DOI: 10.1039/D1QO01217G
您可能还喜欢
如何储存1,2-环己二酮环乙缩醛(CAS号:4746-96-7)?
1,2-环己二酮环乙缩醛应储存在阴凉、干燥、通风良好的地方,避免阳光直射。建议使用密封容器保存,并保持环境温度在室温范围内,远离火源和热源。
Ecopladib(CAS号:381683-92-7)的市场或研究趋势如何?
Ecopladib作为一种新型的药物,主要应用于治疗高胆固醇等疾病。目前,市场和研究趋势显示,Ecopladib因其独特的药理作用而受到关注。随着对心血管疾病治...
2,3-Dimethyl-3H-imidazo[4,5-c]pyridine(CAS号:52538-09-7)通常如何合成?
2,3-二甲基-3H-咪唑[4,5-c]吡啶通常通过咪唑和2,3-二甲基吡啶的缩合反应合成。具体来说,将咪唑和2,3-二甲基吡啶在适当的溶剂中进行加热或加压反应...
2,3,4,5-tetrahydro-1H-3-苯并氮杂环;盐酸盐(CAS号:17379-01-0)的市场或研究趋势如何?
该化合物在药物化学和有机合成中有一定的应用。近年来,随着对新型药物化合物的需求增加,该化合物的研究趋势主要集中在探索其生物活性,尤其是其在神经系统疾病治疗中的潜...
如何储存盐酸甘氨酸丁酯(CAS号:13048-99-2)?
盐酸甘氨酸丁酯应储存在阴凉、干燥、通风良好的地方,避免阳光直射和高温环境,温度应控制在25℃以下。储存容器应密封,避免与空气中的水分和酸性物质接触,以防发生水解...
什么是2-Iodo-N,N-dimethylbenzamide(CAS号:54616-46-5)?
2-碘-N,N-二甲基苯胺是一种有机化合物,化学名为2-Iodo-N,N-dimethylbenzamide。其分子式为C<sub>9</sub>H<sub>1...
5-溴-2-(4H-1,2,4-三唑-4-基)吡啶(CAS号:959240-99-4)的市场或研究趋势如何?
随着医药、农药和新材料领域的发展,该化合物作为关键中间体的应用日益增多。特别是在药物合成中,由于其独特的化学性质,可以用于合成多种药物分子。未来的研究趋势可能集...
2,4-二溴-6-三氟甲基嘧啶(CAS号:785778-00-9)通常如何合成?
2,4-二溴-6-三氟甲基嘧啶通常通过溴化反应合成。首先,将6-三氟甲基嘧啶与溴化剂(如液溴)在适当的溶剂(如二氯甲烷、四氢呋喃)中反应,加入适当的催化剂(如四...
来源期刊
Organic & Biomolecular Chemistry

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.














