A New Benzotriazole‐Mediated Stereoflexible Gateway to Hetero‐2,5‐diketopiperazines |
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| Authors: | Dr. Jean‐Christophe M. Monbaliu Dr. Finn K. Hansen Lucas K. Beagle Dr. Matthew J. Panzner Prof. Dr. Peter J. Steel Dr. Ekaterina Todadze Prof. Dr. Christian V. Stevens Prof. Dr. Alan R. Katritzky |
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| Affiliation: | 1. Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611‐7200 (USA);2. Dept. of Sustainable Organic Chemistry and Technology Faculty of Bioscience Engineering, Ghent University, 9000 Ghent (Belgium);3. Department of Chemistry, University of Akron, Akron, OH 44325 (USA);4. Department of Chemistry, University of Canterbury, Christchurch 8020 (New Zealand);5. Chemistry Department, King Abdulaziz University, Jeddah, 21589 (Saudi Arabia) |
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| Abstract: | Open chain Cbz‐L ‐aa1‐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. |
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| Keywords: | diketopiperazines density functional calculations peptides stereoflexible synthetic methods |
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