A CuAAC-Hydrazone-CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F15%3A00453447" target="_blank" >RIV/61388963:_____/15:00453447 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.mdpi.com/1420-3049/20/10/19310/htm" target="_blank" >http://www.mdpi.com/1420-3049/20/10/19310/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules201019310" target="_blank" >10.3390/molecules201019310</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A CuAAC-Hydrazone-CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations

Popis výsledku v původním jazyce

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid arm with CF2 groups for attachment to the resin and F-19-NMR quantification. This scaffold was attached to a resin and derivatized with model azides and aliphatic, electron-rich or electron-poor aromatic aldehydes. We identified several limitations of the scaffold caused by the instability of hydrazones in acidic conditions, in the presence of copper during CuAAC, and when copper accumulated in the resin. We successfully overcame these drawbacks by optimizing synthetic conditions for the derivatization of the scaffold with aromatic aldehydes. Overall, the new trifunctional scaffold combines CuAAC and hydrazone chemistries, offering a broader chemical space for the d

Název v anglickém jazyce

A CuAAC-Hydrazone-CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations

Popis výsledku anglicky

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid arm with CF2 groups for attachment to the resin and F-19-NMR quantification. This scaffold was attached to a resin and derivatized with model azides and aliphatic, electron-rich or electron-poor aromatic aldehydes. We identified several limitations of the scaffold caused by the instability of hydrazones in acidic conditions, in the presence of copper during CuAAC, and when copper accumulated in the resin. We successfully overcame these drawbacks by optimizing synthetic conditions for the derivatization of the scaffold with aromatic aldehydes. Overall, the new trifunctional scaffold combines CuAAC and hydrazone chemistries, offering a broader chemical space for the d

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GA14-17305S" target="_blank" >GA14-17305S: Mimetika insulinu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

20

Strana od-do

19310-19329

Kód UT WoS článku

000364231200091

EID výsledku v databázi Scopus

2-s2.0-84947550699