A FORMAL TOTAL SYNTHESIS OF THE ACE-INHIBITOR K-13 - AN APPLICATION OF ARENE-RUTHENIUM CHEMISTRY TO COMPLEX CHEMICAL SYNTHESIS

Stoichiometric ruthenium activation of 4-chlorophenylalanine derivativ es toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodi tyrosine derivatives that are synthetic precursors to the ACE inhibito r K-13. An evaluation of carboxyl blocking groups revealed that a 2-br omoethyl eater is the most useful in terms of its compatibility with r uthenium complexation and subsequent nucleophile addition but that its removal is problematic. Conversion to iodoethyl ester using Finkelste in reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethy l group was easily removed on treatment with samarium diiodide.