Unequivocal synthesis of (Z)-alkene and (E)-fluoroalkene dipeptide isosteres to probe structural requirements of the peptide transporter PEPT1.
[reaction: see text] Described is a novel synthetic route for dipeptide isosteres containing (Z)-alkene and (E)-fluoroalkene units as cis-amide bond equivalents via organocopper-mediated reduction of gamma-acetoxy- or gamma,gamma-difluoro-alpha,beta-unsaturated-delta-lactams. The synthesized isosteres were evaluated in terms of their affinities for the peptide transporter PEPT1. trans-Amide isosteres tended to possess higher affinities for PEPT1 as compared to the corresponding cis-amide bond equivalents.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Ayumu
A
Niida
Kenji
K
Tomita
Makiko
M
Mizumoto
Hiroaki
H
Tanigaki
Tomohiro
T
Terada
Shinya
S
Oishi
Akira
A
Otaka
Ken-ichi
K
Inui
Nobutaka
N
Fujii
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D000074011:Peptide Transporter 1; D013237:Stereoisomerism; D027981:Symporters / Q000737:chemistry*
D000475:Alkenes; D004151:Dipeptides; D006845:Hydrocarbons, Fluorinated; D000074011:Peptide Transporter 1; D027981:Symporters