Synthesis of tetrahydro-beta-carbolines and tetrahydroisoquinolines fused to pyrrolidines and solution-phase parallel acylation.
A structurally diverse library of potentially pharmacologically important compounds employing classical synthesis methods 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. Tri- and tetracyclic scaffolds were obtained using the Pictet-Spengler reaction, resulting in hexahydropyrrolo[3,4-c]isoquinolines 1-3, an octahydropyrrolo[3',4':5,6]pyrido[3,4-b]indole 4, and a hexahydrofuro[2,3-d]pyrrolo[3,4-b]pyridine 5. These scaffolds were further derivatized in parallel fashion to make a 32-membered amide library with yields from 62 to 100% (90% average) and purities from 63 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
D000215:Acylation; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry
D002243:Carbolines; D004364:Pharmaceutical Preparations; D011759:Pyrrolidines; D044005:Tetrahydroisoquinolines; C009804:tryptoline