Synthesis of hydantoins and thiohydantoins spiro-fused to pyrrolidines: druglike molecules based on the 2-arylethyl amine scaffold.
The synthesis of a 144-compound library of hydantoins and thiohydantoins spiro-fused to pyrrolidines is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in compounds active in the central nervous system. All possible stereoisomers of the two-stereocenter products are synthesized. The 80-membered hydantoin sublibrary was obtained with yields ranging from 58 to 100% (87% average) and purities from 51 to 100% (87% average) and the 64-membered thiohydantoin sublibrary was obtained with yields ranging from 65 to 100% (89% average) and purities from 67 to 100% (93% 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; D020650:Combinatorial Chemistry Techniques; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013867:Thiohydantoins / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D006827:Hydantoins; D011759:Pyrrolidines; D013141:Spiro Compounds; D013867:Thiohydantoins