A new benzotriazole-mediated stereoflexible gateway to hetero-2,5-diketopiperazines.

Jean-Christophe M Monbaliu, Finn K Hansen, Lucas K Beagle, Matthew J Panzner, Peter J Steel, Ekaterina Todadze, Christian V Stevens, Alan R Katritzky

Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.

Chemistry (Weinheim an der Bergstrasse, Germany) 2012 Feb 27

filter terms:

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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Jean-Christophe M Monbaliu, Finn K Hansen, Lucas K Beagle, Matthew J Panzner, Peter J Steel, Ekaterina Todadze, Christian V Stevens, Alan R Katritzky. A new benzotriazole-mediated stereoflexible gateway to hetero-2,5-diketopiperazines. Chemistry (Weinheim an der Bergstrasse, Germany). 2012 Feb 27;18(9):2632-8