Simple, versatile and highly diastereoselective synthesis of 1,3,4-trisubstituted-2-oxopiperazine-containing peptidomimetic precursors.
The selective O-deprotection of (1'S)-4-(tert-butoxycarbonyl)-1-[1'-phenylmethyloxymethyl-2'-[(tert-butyldimethylsilyl)oxy]ethyl]-2-oxopiperazine furnished an enantiomerically pure alcohol whose regio- and diastereoselective C3-alkylation yielded either (3R)- or (3S)-1,3,4-trisubstituted-2-oxopiperazines in high diastereomeric purity. These derivatives were efficiently transformed into (1'R)- or (1'S)-peptide templates utilizable to prepare peptidomimetics. This method provides easy access to each 1,3,4-trisubstituted-2-oxopiperazine diastereomer and facilitates, through the large choice of substituents at the 3-position together with the chemistry that can be performed on the N1 substituent, the preparation of a large number of diastereomerically pure constrained peptidomimetics from a single precursor.
Franceschini
Nicolas
N
Laboratoire de Chimie Thérapeutique, EA 2629, 1 Rue des Louvels, 80000, Amiens, France.
Sonnet
Pascal
P
Guillaume
Dominique
D
D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007769:Lactams; D010455:Peptides; D010879:Piperazines