Improved synthesis, resolution, absolute configuration determination and biological evaluation of HLM006474 enantiomers

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Rosales-Hurtado, Miyanou¹  Lebeau, Alexandre¹  Bourouh, Cyril⁴  Cebrian-Torrejon, Gerardo¹  Albalat, Muriel²  Jean, Marion²  Naubron, Jean-Valere³  Annicotte, Jean-Sebastien⁴  Benfodda, Zohra¹  Meffre, Patrick¹ 

[1] Univ Nimes, CHROME EA7352, Rue Dr G Salon, F-300 Nimes 1, France

[2] Aix Marseille Univ, CNRS, Cent Marseille, iSm2, Marseille, France

[3] Aix Marseille Univ, CNRS, Cent Marseille, FSCM,Spectropole, Marseille, France

[4] Univ Lille, Inst Pasteur Lille, EGID, CNRS UMR 8199, F-59000 Lille, France

关键词: HLM006474 enantiomers;    Betti reaction;    Solvent-free reaction;    Microwave assisted synthesis;    Absolute configuration determination;    Biological activity;   

DOI  :  10.1016/j.bmcl.2018.12.037

来源: Elsevier

【 摘 要 】

An improved green synthesis of the E2F inhibitor HLM0066474 is described, using solvent-free and microwave irradiation conditions. The two enantiomers are separated using semi-preparative separation on Chiralpak ID and their absolute configuration is determined by vibrational circular dichroism (VCD) analysis. Biological evaluation of both enantiomers on E2F1 transcriptional activity reveals that the (+)-R, but not the (-)-S enantiomer is biologically active in repressing E2F1 transcriptional activity.

【 授权许可】

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