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A New Benzotriazole‐Mediated Stereoflexible Gateway to Hetero‐2,5‐diketopiperazines
Author(s) -
Monbaliu JeanChristophe M.,
Hansen Finn K.,
Beagle Lucas K.,
Panzner Matthew J.,
Steel Peter J.,
Todadze Ekaterina,
Stevens Christian V.,
Katritzky Alan R.
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201103143
Subject(s) - diketopiperazines , chemistry , benzotriazole , tandem , epimer , kinetics , combinatorial chemistry , stereochemistry , organic chemistry , materials science , physics , quantum mechanics , composite material
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.