Synthesis and opiate activity of pseudo-tetrapeptides containing chiral piperazin-2-one and piperazine derivatives.
Enantiomeric piperazin-2-one derivatives, N,N'-ethylene-bridged alanylphenylalanines (1a or 1b), were synthesized using (S)- or (R)-alanine and phenylalanine as starting materials, and were inserted into the second and third positions of enantiomeric pseudo-tetrapeptides (P1a- or P1b-OEt). The corresponding piperazine derivatives (1a- or 1b-sRed) obtained by selective BH3 reduction of the amide carbonyl groups of 1a or 1b were similarly inserted into the same positions of tetrapeptides (P1a- and P1b-sRed). Enantiomeric N,N'-ethylene-bridged tyrosyltyrosine derivatives (2a or 2b) obtained from (S)- or (R)-tyrosine were also inserted into the first and second positions of two pairs of enantiomeric tetrapeptides (P2a- and P2b-OEt or P'2a- and P'2b-OEt). The opiate activities of the eight peptides thus obtained were studied by use of the mouse vas deferens and the guinea pig ilcum assays in order to elucidate the structure-activity relationships of these peptides, especially with respect to stereochemistry.
Yamashita
T
T
Department of Chemistry, Faculty of Science, Osaka City University, Japan.
Tsuru
E
E
Banjyo
E
E
Doe
M
M
Shibata
K
K
Yasuda
M
M
Gemba
M
M
D000409:Alanine / Q000737:chemistry; D000818:Animals; D001681:Biological Assay; D001896:Boron Compounds / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009294:Narcotics / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010649:Phenylalanine / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001896:Boron Compounds; D001952:Bridged-Ring Compounds; D009294:Narcotics; D009842:Oligopeptides; D010879:Piperazines; D010649:Phenylalanine; D000409:Alanine