title: Multicomponent, Mannich-type assembly process for generating novel, biologically-active 2-arylpiperidines and derivatives.
abstract: A multicomponent, Mannich-type assembly process commencing with commercially available bromobenzaldehydes was sequenced with [3+2] dipolar cycloaddition reactions involving nitrones and azomethine ylides to generate collections of fused, bicyclic scaffolds based on the 2-arylpiperidine subunit. Use of the 4-pentenoyl group, which served both as an activator in the Mannich-type reaction and a readily-cleaved amine protecting group, allowed sub-libraries to be prepared through piperidineN-functionalization and cross-coupling of the aryl bromide. A number of these derivatives displayed biological activities that had not previously been associated with this substructure. Methods were also developed that allowed rapid conversion of these scaffolds to novel, polycyclic dihydroquinazolin-2-ones, 2-imino-1,3-benzothiazinanes, dihydroisoquinolin-3-ones and bridged tetrahydroquinolines.
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
authors.forename: Simon
authors.initials: S
authors.lastname: Hardy
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Martin
keywords: Bioactive compounds; Compound libraries; Dipolar cycloadditions; Diversity oriented synthesis; Multicomponent assembly process