Stereoselective synthesis of 3,6-disubstituted-3,6-dihydropyridin-2-ones as potential diketopiperazine mimetics using organocopper-mediated anti-SN2' reactions and their use in the preparation of low-molecule CXCR4 antagonists.
Organocopper-mediated anti-SN2' reactions of gamma-phosphoryloxy-alpha,beta-unsaturated-delta-lactams were used to prepare highly functionalized diketopiperazine mimetics. The substrate phosphates 24, 32, and 47 were prepared from alpha-amino acid-derived allylic alcohols 10 by a sequence of reactions that included ring-closing metathesis. In the reactions of phosphates with organocopper reagents, the addition of LiCl dramatically improved anti-SN2' selectivity, indicating that an organocopper cluster containing lithium chloride plays an important role in the determination of regioselectivity. This reaction system was applied to the preparation of novel low molecular weight CXCR4-chemokine receptor antagonists.
Niida
Ayumu
A
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Tanigaki
Hiroaki
H
Inokuchi
Eriko
E
Sasaki
Yoshikazu
Y
Oishi
Shinya
S
Ohno
Hiroaki
H
Tamamura
Hirokazu
H
Wang
Zixuan
Z
Peiper
Stephen C
SC
Kitaura
Kazuo
K
Otaka
Akira
A
Fujii
Nobutaka
N