Biometal Corrole Active Esters and their Amino Acid and Peptide Conjugates

The synthesis of a series of A(2)B-corroles with 4-carboxyphenyl substituent is described. The macrocycles are prepared from dipyrromethanes and 4-formylbenzoic acid under Gryko conditions. Redox active biometal complexes are formed from the corrole carboxylic acids with the metal ions of cobalt, iron, and manganese, but not with copper. From all free corrole bases and metal complexes, the respective active esters are obtained in good yields by condensation with NHS (N-hydroxysuccinimide) and EDC (1-ethyl-3-dimethylaminopropyl-carbodiimide). Starting from the active esters of the free corrole bases, the copper corroles are accessible in acceptable yields. Oxidation- and spin states of the biometal corroles correspond to those of simple corroles and are confirmed spectroscopically and magnetically. Ethylenediamine is efficiently coupled with the corrole carboxylic acids by EDC, whereby selective two-fold coupling is observed. For the coupling to N(alpha)Boc-lysine as well as N(alpha)Fmoc-lysine the use of corrole active esters is advantageous. The metalation of corroles carryingN-protected lysine side chains turns out to proceed only with loss of most of the material. Here, the coupling of the amino acid building block with the metal corrole active ester proved to be the synthetically more applicable variant. The resulting N(alpha)Fmoc-lysine conjugates of both a free base corrole and a manganese corrole complex are shown to be suitable for use in Merrifield solid phase peptide synthesis.