Solution-phase parallel annulation of (thio)hydantoins to tetrahydroisoquinolines and tetrahydro-beta-carbolines containing the 2-arylethyl amine scaffold.
The one-step solution-phase parallel synthesis of two structurally diverse libraries of pharmacologically important compounds is described. The presented compounds combine three privileged structures: the 2-arylethyl amine moiety, a tetrahydro(hetero)areno[c]pyridine, and a (thio)hydantoin. These compounds are synthesized by annulation of a hydantoin or a 2-thiohydantoin ring to tri- or tetracyclic scaffolds, containing the 2-arylethyl amine moiety and a tetrahydroisoquinoline, a tetrahydro-beta-carboline, or a tetrahydrofuro[3,2-c]pyridine. The annulation leads to pharmacologically relevant structural motifs such as imidazopyrroloisoquinolines, dioxoloimidazopyrroloisoquinolines, furoimidazopyrrolopyridines, and imidazopyrrolopyridoindoles. Both libraries were obtained with quantitative yields. The 36-membered hydantoin library was obtained with purities from 57 to 100% (90% average) and the 32-membered thiohydantoin library with purities from 73 to 100% (94% average).
Blanco-Ania
Daniel
D
Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, The Netherlands.
Hermkens
Pedro H H
PH
Sliedregt
Leo A J M
LA
Scheeren
Hans W
HW
Rutjes
Floris P J T
FP
D000588:Amines / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013867:Thiohydantoins / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D002243:Carbolines; D004364:Pharmaceutical Preparations; D044005:Tetrahydroisoquinolines; D013867:Thiohydantoins; C009804:tryptoline