Isosteric dipeptides containing ether bond

摘要

The present invention relates to novel isosteric dipeptides containing ether bond of the general formula I, in which Re1 represents a protecting group of a primary amino group that can be split off either in acidic or alkali manner, by Boc, Z, Nps, Fmoc; Re2 represents a side chain of N-terminal part of an isosteric dipeptide resulting from Gly, Ala, Abu, Ile, Val, Leu, Nle, Neo, Ser(Z), Thr(Z), Asn, Gln, Arg(Tos), Lys(BzlCli2), Orn(BzlCli2), Dbu(BzlCli2), Met, Phe, Pro, Tyr(Bzl), His(Boc), Trp(For); Re3 represents a side chain of N-terminal part of C-terminal part of an isosteric dipeptide resulting from Ala, Abu, Ile, Val, Leu, Nle, Neo, Ser(Z), Thr(Z), Asn, Gln, Arg(Tos), Lys(BzlCli2), Orn(BzlCli2), Dbu(BzlCli2), Met, Phe, Pro, Tyr(Bzl), His(Boc), Trp(For); Re4 represents alkyl containing 1 to 4 carbon atoms either in straight or branched arrangement, and a process for preparing these isosteric dipeptides, wherein the preparation process is characterized in that the protected aminoalcohol of the general formula II is brought into reaction with {alpha}-diazo derivative of carboxylic acid of the general formula III in the presence of the MeXi2 catalyst, wherein Me represents Rhe2+ or Cue2+ and X represents anion, preferably acetate, at a temperature of 80 degC and the obtained diastereoisomeric mixture of the protected isosteric pseudo-dipeptides is then divided by preparative, high-efficiency chromatography to individual optical isomers. These isomers are then directly employable for synthesis of mimetic peptides.