title: A new benzotriazole-mediated stereoflexible gateway to hetero-2,5-diketopiperazines.
abstract: Open chain Cbz-L-aa(1)-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5-diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results.
authors.affiliation: Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
authors.forename: Jean-Christophe M
authors.initials: JC
authors.lastname: Monbaliu
authors.forename: Finn K
authors.initials: FK
authors.lastname: Hansen
authors.forename: Lucas K
authors.initials: LK
authors.lastname: Beagle
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Steel
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Todadze
authors.forename: Christian V
authors.initials: CV
authors.lastname: Stevens
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D002851:Chromatography, High Pressure Liquid; D054659:Diketopiperazines / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry*
chemical_list: D054659:Diketopiperazines; D014230:Triazoles; C012771:benzotriazole; D011392:Proline