Generation of Multimillion Chemical Space Based on the Parallel Groebke-Blackburn-Bienaymé Reaction

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2024 Jul 30

PMID 39076290

Authors

Evgen V Govor

Vasyl Naumchyk

Ihor Nestorak

Dmytro S Radchenko

Dmytro Dudenko

Yurii S Moroz

Olexiy D Kachkovsky

Oleksandr O Grygorenko

Affiliations

Soon will be listed here.

Abstract

Parallel Groebke-Blackburn-Bienaymé reaction was evaluated as a source of multimillion chemically accessible chemical space. Two most popular classical protocols involving the use of Sc(OTf) and TsOH as the catalysts were tested on a broad substrate scope, and prevalence of the first method was clearly demonstrated. Furthermore, the scope and limitations of the procedure were established. A model 790-member library was obtained with 85% synthesis success rate. These results were used to generate a 271-Mln. readily accessible (REAL) heterocyclic chemical space mostly containing unique chemotypes, which was confirmed by comparative analysis with commercially available compound collections. Meanwhile, this chemical space contained 432 compounds that already showed biological activity according to the ChEMBL database.

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