Efficient routes to the Arnstein's tripeptide δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine (LLD ACV) from the oxidation products of L-lysine derivatives

Abstract

Two efficient syntheses of the linear tripeptide precursor of penam and cephem antibiotics are presented. The routes are characterised by the use of L-lysine derivatives, Z-L-Lys(Z)-OH and H-L-Lys(Z)-OH as starting materials. By the permanganate oxidation the protected side chain amino grouping in L-lysine derivatives is transformed into the benzyloxycarbonylcarbamoyl substituent with formation of Z-L-Aad(NHZ)-OH and H-L-Aad(NHZ)-OH compounds. Both oxidation products are easily transformed into [N, Cα]-diprotected derivatives. Subsequent condensation at the δ-carboxy group afforded protected LLD ACV tripeptide.