当前位置: X-MOL 学术ACS Comb. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Gold-Catalyzed Solid-Phase Synthesis of 3,4-Dihydropyrazin-2(1H)-ones: Relevant Pharmacophores and Peptide Backbone Constraints
ACS Combinatorial Science ( IF 3.903 ) Pub Date : 2017-09-12 00:00:00 , DOI: 10.1021/acscombsci.7b00117
Adam Přibylka 1 , Viktor Krchňák 1, 2
Affiliation  

Here, we report the efficient solid-phase synthesis of N-propargyl peptides using Fmoc-amino acids and propargyl alcohol as key building blocks. Gold-catalyzed nucleophilic addition to the triple bond induced C–N bond formation, which triggered intramolecular cyclization, yielding 1,3,4-trisubstituted-5-methyl-3,4-dihydropyrazin-2(1H)-ones. Conformations of acyclic and constrained peptides were compared using a two-step conformer distribution analysis at the molecular mechanics level and density functional theory. The results indicated that the incorporation of heterocyclic molecular scaffold into a short peptide sequence adopted extended conformation of peptide chain. The amide bond adjacent to the constraint did not show significant preference for either cis or trans isomerism. Prepared model compounds demonstrate a proof of concept for gold-catalyzed polymer-supported synthesis of variously substituted 3,4-dihydropyrazin-2(1H)-ones for applications in drug discovery and peptide backbone constraints.

中文翻译:

金催化的3,4-二氢吡嗪-2(1 H)-ones固相合成:相关药理和肽骨干约束。

在这里,我们报道了使用Fmoc-氨基酸和炔丙醇作为关键组成部分的N-炔丙基肽的高效固相合成。金催化的亲核加成到三键诱导的C–N键形成,这引发分子内环化,产生1,3,4-三取代-5-甲基-3,4-二氢吡嗪-2(1 H)-那些。在分子力学水平和密度泛函理论上,使用两步构象分布分析比较了无环和受约束肽的构象。结果表明,将杂环分子支架掺入短肽序列中采用了肽链的扩展构象。与限制条件相邻的酰胺键对顺式或反式异构均无明显偏爱。制备的模型化合物证明了金催化的聚合物支持的各种取代的3,4-二氢吡嗪-2(1 H)-one的合成在药物发现和肽主链约束中的应用。
更新日期:2017-09-12
down
wechat
bug