Synthesis and library construction of privileged tetra-substituted Δ5-2-oxopiperazine as β-turn structure mimetics.
In this study, we developed an efficient and practical procedure for the synthesis of tetra-substituted Δ5-2-oxopiperazine that mimics the bioactive β-turn structural motif of proteins. This synthetic route is robust and modular enough to accommodate four different substituents to obtain a high level of molecular diversity without any deterioration in stereochemical enrichment of the natural and unnatural amino acids. Through the in silico studies, including a distance calculation of side chains and a conformational overlapping of our model compound with a native β-turn structure, we successfully demonstrated the conformational similarity of tetra-substituted Δ5-2-oxopiperazine to the β-turn motif. For the library construction in a high-throughput manner, the fluorous tag technology was adopted with the use of a solution-phase parallel synthesis platform. A 140-membered pilot library of tetra-substituted Δ5-2-oxopiperazines was achieved with an average purity of 90% without further purification.
Department of Chemistry and ‡Department of Biophysics and Chemical Biology, Seoul National University , Seoul 151-747, Korea.
Jonghoon
J
Kim
Won Seok
WS
Lee
Jaeyoung
J
Koo
Jeongae
J
Lee
Seung Bum
SB
Park
D000596:Amino Acids / Q000737:chemistry; D032701:Biomimetics; D020650:Combinatorial Chemistry Techniques; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D000596:Amino Acids; D010879:Piperazines; D011506:Proteins