From Lewis Acid Catalysis to Peptide Synthesis

Catalytic peptide synthesis is the long-standing problems for chemical synthesis.  One of the most difficult problems for previous synthesis is that the required activated carboxylic acid which caused 1) the racemization of the product, 2) the equimolar usage of the activated ester unit results significant amounts of side products, 3) difficult for general ligation of peptides, and 4) overwhelmingly high price. Generally, Lewis acid catalyst interacts the basic site of molecule and activates another carbonyl group nearby.  This activation process will avoid any racemization path since the coordination of Lewis acid to the methyl ester may not be attacked by the amide oxygen intramoleculaly.  Lewis acid catalyst can be used various metal alkoxides such as Ta or Nb alkoxides with 1-10 mol% loading.  The proposed process has huge potential for future drug industry.