1989 Volume 37 Issue 4 Pages 912-919
A novel approach to the mimicking of enzyme-catalyzed bond-forming reactions has been examined using multi-functionalized chiral crown ethers. In addition to the 18-crown-6 moiety as a binding site, the hosts have one thiol and one thio ester with an N-protected α-amino acid or a peptide, and have successfully achieved peptide synthesis in an enzyme-mimetic reaction mode. This new method involves the following three key reactions. (1) Intra-complex thiolysis : the host carries out the rapid intra-complex thiolysis of α-amino acid ester salts to form the dithioester, corresponding to the assembly of two guests by the host. (2) Amide formation : intramolecular aminolysis occurs between the bound guests to form the amide bond. (3) Peptide chain elongation : as the thiol reactive group is regenerated, the above two reactions are repeated to elongate the peptide chain. Formal turnover of the enzyme model has been demonstrated by the synthesis of a tetrapeptide derivative by the repetition of the above processes.
