Tandem N-acyliminium/Pictet-Spengler/intramolecular Diels-Alder reaction:: an expedient route to hexacyclic tetrahydro-β-carbolines

A mild and efficient synthesis of rigid hexacyclic nitrogen heterocycles with tetrahydro-beta-carboline skeleton is described. Acylation of the imines 7a-d, prepared from tryptamine (5) and furaldehydes 6a-d, with maleic anhydride at room temperature provided the corresponding hexacyclic nitrogen heterocycles 10a-d via a tandem N-acyliminium/Pictet-Spengler/IMDA reaction. In this tandem approach, five stereocenters, including a quaternary center and three rings are generated with excellent stereoselectivity. Key to the success of this approach, is the use of furaldehyde and maleic anhydride as the aldehyde and anhydride components, respectively. Transformation of the free acid to the corresponding amide, ester and alcohol is also studied. (C) 2002 Elsevier Science Ltd. All rights reserved.