A New Benzotriazole-Mediated Stereoflexible Gateway to Hetero-2,5-diketopiperazines

作者：Monbaliu Jean Christophe M; Hansen Finn K; Beagle Lucas K; Panzner Matthew J; Steel Peter J; Todadze Ekaterina; Stevens Christian V; Katritzky Alan R^*

来源：Chemistry - A European Journal, 2012, 18(9): 2632-2638.

DOI：10.1002/chem.201103143

• diketopiperazines
• density functional calculations
• peptides
• stereoflexible
• synthetic methods

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 (6975?%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (6572?%). 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.

• 出版日期2012-2