Amino acid-based synthesis of trifluoromethylalkene dipeptide isosteres by alcohol-assisted nucleophilic trifluoromethylation and organozinc-copper-mediated S(N)2' alkylation.
A novel synthetic approach to Xaa-Yaa-type (Z)-trifluoromethylalkene dipeptide isostere (CF(3)-ADI) has been developed. Starting from readily available l-phenylalanine and l-alanine, several CF(3)-ADIs were obtained through nucleophilic trifluoromethylation of gamma-keto esters and S(N)2' alkylation of trifluoromethylated mesylates. The influence of a trifluoromethyl group on the diastereoselectivity of the S(N)2' reaction is also discussed.
Kobayashi
Kazuya
K
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Narumi
Tetsuo
T
Oishi
Shinya
S
Ohno
Hiroaki
H
Fujii
Nobutaka
N
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis*; D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis*; D008698:Mesylates / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D000475:Alkenes; D000596:Amino Acids; D004151:Dipeptides; D008698:Mesylates; D009942:Organometallic Compounds; D010649:Phenylalanine; D003300:Copper; D015032:Zinc; D000409:Alanine