Stereoselective synthesis of novel dipeptide beta-turn mimetics targeting melanocortin peptide receptors.
[reaction: see text] The novel dipeptide beta-turn mimetic, 4,8-disubstituted azabicyclo[4.3.0]nonane amino acid ester (15), has been synthesized to serve as a peptide mimetic of the dipeptide Phe-Arg, which contains two important pharmacophore elements in melanotropin peptides. Introduction of side-chain functionality at C-8 was achieved by using beta-functionalized pyroglutamate (8) as a synthetic precursor. The side chain at C-4 was introduced by bromination of dehydroamino acid intermediate (10) followed by Suzuki cross-coupling.
Zhang
Junyi
J
Department of Chemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, USA.
Xiong
Chiyi
C
Ying
Jinfa
J
Wang
Wei
W
Hruby
Victor J
VJ
D000595:Amino Acid Sequence; D040761:Biomimetic Materials / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011761:Pyrrolidonecarboxylic Acid / Q000138:chemical synthesis; D018043:Receptors, Corticotropin / Q000737:chemistry*; D044101:Receptors, Melanocortin; D013237:Stereoisomerism
D004151:Dipeptides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D009074:Melanocyte-Stimulating Hormones; D011761:Pyrrolidonecarboxylic Acid