Tetsushi Yamashita

Enantioselective transport of amino acid ester salts by macrocyclic pseudopeptides containing N, N′-ethylene-bridged-dipeptide units

Macrocyclic pseudopeptides containing N,N′-ethylene-bndged-dipeptide units exhibited specific transport properties toward several amino acid ester salts, while they rarely transported K− or other metal cations. In particular, a 36-membered pseudopeptide extracted amino acid ester salts in an enantioselective fashion and mediated their enantioselective transport.

Synthesis of met- and leu-enkephalin analogues containing chiral N,N′-ethylene-bridged phenylalanyl-methionine and -leucine

Conformationally constrained N,N′-ethylene-bridged dipeptides (eXX′) were conveniently synthesized in two steps using (R)- or (S)-phenylalanine (X = F) and -methionine (X′= M)[-leucine (X′= L)] as starting materials.These dipeptides are diastereoisomeric or enantiomeric, and were used as the carboxyl terminal residues of enkephalin analogues [H–tyrosyl–D-alanyl–glycyI–eXX′–OEt]. The opiate activities of these pentapeptides were examined preliminarily by the mouse vas deferens assay, suggesting that these enkephalin analogues possess receptor- binding affinities.

Preparations ofN, N′-ethylene-bridged dipeptides(eXX) constructed from (S)-methionine, -tryptophan, -tyrosine and-N(ɛ)-benzyloxycarbonyllysine through acid-catalyzed cyclization

SummaryN, N′-Ethylene-bridged bis-(S)-methionine[(2S, 7S)-2, 7-bis(2-methyl-thioethyl)-3,6-diazaoctanedioic acid] derived from (S)-methionine and 1,2-dibromoethane was cyclized and esterified simultaneously in boiling ethanol in the presence of an appropriate amount of strong acid such asp-toluenesulfonic acid, affording a cyclic compound,N, N′-ethylene-bridged (S)-methionyl-(S)-methionine ethyl ester {ethyl(2S, 3′S)-4-(methylthio)-2-[2′-oxo-3′-(2-methylthioethyl)-1′-piperazinyl] butanoate}, exclusively in 80–90% yields. It was also found that, by applying this method, 70–80% yields of the otherN, N′-ethylenebridged dipeptides containing (S)-tryptophan, -tyrosine and -N(ɛ)-benzyloxycarbonyllysine were obtained.

CONFORMATIONAL STUDY OF STRUCTURALLY CONSTRAINED 18-MEMBERED CYCLIC PEPTIDE CONTAINING N,N'-ETHYLENE-BRIDGED-(S)-PHENYLALANYL-(S)-PHENYLALANINE

Abstract The conformation of cyclo[(2S,3′S)-2-(3′-benzyl-2′-oxopiperazin-1′-yl)-3-phenyl-propanoyl-glycyl]2 crystallized with two water molecules (C44H46N6O6 2H2O) is compared with its solution structure and those of cyclo[(2S, 3′S)-2-(3′-methyl-2′-oxopiperazin-1′-yl)-propanoyl-glycyl]2.