EFFICIENT SYNTHESIS OF CONFORMATIONALLY CONSTRAINED PEPTIDOMIMETICS CONTAINING 2-OXOPIPERAZINES

The enantioselective synthesis of a series of peptides containing the 3-substituted 2-oxopiperazine system is reported. The method involves a direct diastereoselective alkylation of the N-(hydroxyalkyl)-2-oxopi perazine 3, prepared in three steps from methyl L-leucinate in 38% yie ld, followed by oxidation of the hydroxyl function. Esterification of the resulting acids 11 and then deprotection and acylation of N-4 affo rded tripeptide analogues 16 substituted by a large variety of alkyl s ide chains at the 2-position of the 2-oxopiperazine.