Gold-Catalyzed Solid-Phase Synthesis of 3,4-Dihydropyrazin-2(1H)-ones: Relevant Pharmacophores and Peptide Backbone Constraints

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F17%3A73584394" target="_blank" >RIV/61989592:15310/17:73584394 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.acs.org/doi/ipdf/10.1021/acscombsci.7b00117" target="_blank" >http://pubs.acs.org/doi/ipdf/10.1021/acscombsci.7b00117</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acscombsci.7b00117" target="_blank" >10.1021/acscombsci.7b00117</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Gold-Catalyzed Solid-Phase Synthesis of 3,4-Dihydropyrazin-2(1H)-ones: Relevant Pharmacophores and Peptide Backbone Constraints

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Gold-Catalyzed Solid-Phase Synthesis of 3,4-Dihydropyrazin-2(1H)-ones: Relevant Pharmacophores and Peptide Backbone Constraints

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA16-06446S" target="_blank" >GA16-06446S: Od aminokyselin k molekulárním skafoldům inspirovaných přírodou</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Combinatorial Science

ISSN

2156-8952

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

681-686

Kód UT WoS článku

000415392200002

EID výsledku v databázi Scopus

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