Efficient synthesis of conformationally constrained peptidomimethics containing 2-oxpiperazines

摘要

The enantionselective 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-(hydroxy- alkyl)-2-oxopiperazine 3, prepared in three steps from methyl L-leucinate in 38/100 yield, followed by oxidation of the hydroxyl function. Esterification of the resulting acids 11 and then deprotection and acylation of N-4 afforded tripeptide analogues 16 substituted by a large variety of alkyl side chains at the 3-position of the 2-oxopiperazine.