Solid-supported synthesis of putative peptide beta-turn mimetics via Ugi reaction for diketopiperazine formation.
The scope and limitations of the solid-supported synthesis of a bicyclic diketopiperazine, an internal, putative peptide beta-turn mimetic, are presented. The 4CC multicomponent Ugi reaction of alpha-N-Boc-diaminopropionic acid resin ester (an amine input), optically active alpha-bromoacid, aldehyde, and isocyanide is the key step in the proposed synthetic protocol. Application of cyclitive cleavage as the final step led to desired products in high purity.
Golebiowski
Adam
A
Combinatorial Chemistry Group, Health Care Research Center, Procter & Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, P.O. Box 8006, Mason, Ohio 45040-8006, USA. golebiowski.a@pg.com
Jozwik
Julita
J
Klopfenstein
Sean R
SR
Colson
Anny-Odile
AO
Grieb
Arthur L
AL
Russell
Anne F
AF
Rastogi
Vinit L
VL
Diven
Conrad F
CF
Portlock
David E
DE
Chen
Jack J
JJ
D040761:Biomimetic Materials / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D007659:Ketones / Q000138:chemical synthesis*; D008958:Models, Molecular; D018716:Molecular Mimicry; D019151:Peptide Library; D010879:Piperazines / Q000138:chemical synthesis*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D007659:Ketones; D019151:Peptide Library; D010879:Piperazines