Development of highly efficient, selective, and practical synthetic method of pseudo-peptides possessing anti-tumour activity.

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1.We found a convenient method for the transformation of undesired anti-amino alcohols into desired cis-2-vinylaziridines, which are key synthetic intermediates for biologically active(E)-alkene peptide-isosteres, via trans-2-vinylaziridines by Pd(0)-catalyzed equilibration reaction.2.Various cis-aziridine derivatives were efficiently synthesized from 4-alkyl-5-vinyloxazilidin-2-ones and β-aziridinyl-α, β-unsaturated esters by the Pd(0)-mediated equilibration reaction.3.The ab initio calculations revealed that cis-β-aziridinyl-α, β-unsaturated esters, possessing cis-(E)-configuration, are more stable than their diastereoisomers. These results are compatible with the experimental results.4.In combination with Pd(0)-mediated isomerization and the regio- and stereo-specific SN2-type ring-opening reactions of β-aziridinyl-α,β-unsaturated esters with Brφnsted acids, the completely stereocontrolled synthetic process for(L,L)-, (L,D)-, (D,D)-, and (D,L)-type(E)-alkene dipeptide isosteres starting from amino acids has been established.5.Various peptide-isosteres containing Trp-, Asp-, Cys-, and Glu-analogues were synthesized by the reductive alkylation with organocopper reagents or by the nucleophilic alkylation with zinc-copper mixed reagents.6.Several bombesin analogues with(E)-alkene bond were prepared by replacing a constituent amino acid of bombesin with the synthesized peptide-isosteres, and these compounds were revealed to be potent bombesin receptor antagonists.