title: A step-economical multicomponent synthesis of 3D-shaped aza-diketopiperazines and their drug-like chemical space analysis.
abstract: A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(i)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs. Moreover, an analysis of their 3D molecular descriptors and "drug-likeness" properties highlights not only their originality in the chemical space of aza-heterocycles but also their great potential for medicinal chemistry.
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Regenass
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Riché
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Péron
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Rognan
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hibert
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France. nicolas.girard@unistra.fr dominique.bonnet@unistra.fr.
authors.forename: Dominique
authors.identifier: http://orcid.org/0000-0002-8252-9199
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001372:Aza Compounds; D054659:Diketopiperazines; D012663:Semicarbazides; D012238:Rhodium