Scalable (Enantioselective) Syntheses of Novel 3-Methylated Analogs of Pazinaclone, (<i>S</i>)-PD172938 and Related Biologically Relevant Isoindolinones
Antonia Di Mola,
Giorgia Nicastro,
Lorenzo Serusi,
Rosanna Filosa,
Mario Waser,
Antonio Massa
Affiliations
Antonia Di Mola
Dipartimento di Chimica e Biologia “A. Zambelli”, Università degli Studi di Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy
Giorgia Nicastro
Dipartimento di Chimica e Biologia “A. Zambelli”, Università degli Studi di Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy
Lorenzo Serusi
Dipartimento di Chimica e Biologia “A. Zambelli”, Università degli Studi di Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy
Rosanna Filosa
Dipartimento di Scienze e Tecnologia, Università degli Studi del Sannio, Via De Sanctis, 82100 Benevento, Italy
Mario Waser
Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstr. 69, 4040 Linz, Austria
Antonio Massa
Dipartimento di Chimica e Biologia “A. Zambelli”, Università degli Studi di Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy
Herein, we report the application of an efficient and practical K2CO3 promoted cascade reaction of 2-acetylbenzonitrile in the synthesis of novel 3-methylated analogs of Pazinaclone and PD172938, belonging to isoindolinones heterocyclic class bearing a tetrasubstituted stereocenter. Organocatalytic asymmetric synthesis of the key intermediate and its transformation into highly enantioenriched 3-methylated analog of (S)-PD172938 was also developed. These achievements can be of particular interest also for medicinal chemistry, since the methyl group is a very useful structural modification in the rational design of new and more effective bioactive compounds.
