Design of directing groups toward the distal functionalization within aromatic amino acids

Abstract

[EN] Late-stage C–H functionalization has arisen as a powerful instrument for the rapid preparation of libraries of analogues derived from bioactive compounds and for the improvement of biological activity and metabolic stability. Despite the wealth of reports in the field, the site-selective remote modification of both phenylalanine (Phe) and tyrosine (Tyr) compounds upon metal catalysis remains comparatively overlooked. Thus, the main goal of this work relies on the development of a protocol for the meta C(sp2)−H functionalization of Tyr and Phe in a late-stage fashion. In particular, a strategy for the Pd-catalyzed meta C(sp2)−H functionalization was studied for Tyr and Phe units. This strategy involves the design of a removable directing group (DG) connected to the amino acid unit that enables the meta C(sp2)−H activation. A pyridine and benzonitrile-containing template were established as DGs on the N-terminal position of the Tyr and Phe unit. Nevertheless, no optimal protocol has been developed fort the remote C(sp2)−H functionalization

[EU] Azken etapako C–H funtzionalizazioa tresna indartsu gisa sortu da konposatu bioaktiboetatik eratorritako analogoak azkar biltzeko. Modu honetan, jarduera biologikoa eta egonkortasun metabolikoa hobea daukaten analogoak lortu daitezke. Nahiz eta txostenak ugari izan, fenilalaninaren (Phe) eta tirosinaren (Tyr) katalisi metalikoaren bitartez urruneko eraldaketa selektiboa ez da momentuz aztertu. Horrela, lan honen helburu nagusia Tyr eta Phe-ren meta C(sp2 )−H funtzionalizaziorako protokolo bat garatzea da.

Zehazki, Pd-katalizatutako meta C(sp2)−H estrategia bat ikertu da Tyr eta Phe-ren funtzionalizaziorako. Estrategia honen bidez, aminoazidoei konektatutako talde zuzentzaile desmuntagarri bat diseinatu nahi da, meta C(sp2)−H-ren aktibazioa aukera emango duena. Piridinina eta benzonitrilo taldeak ezarri ziren talde zuzentzaile gisa Tyr and Phe unitatearen N-posizio terminalean. Hala ere, ez dugu protokolo optimorik garatu urruneko C(sp2)−H funtzionalizaziorako.