The role of protecting groups is crucial in peptide and nucleic acid synthesis, especially in the synthesis of complex molecules such as peptide nucleic acids (PNA). PNA is a DNA analogue with a peptide like backbone, whose main backbone is composed of N (2-aminoethyl) - glycine and nucleic acid bases connected by methylene carbonyl groups. In the synthesis process of PNA, the use of protective groups is to protect specific functional groups, prevent them from being consumed in unnecessary reactions, and ensure efficient synthesis and purification of target molecules.
Selection and Function of Protective Bases
Protecting amino acids: In the synthesis of PNA, the guanidine group of arginine has strong nucleophilicity and alkalinity, and needs to be protected to prevent its removal under acidic and alkaline conditions. Common protective groups include tert butoxycarbonyl, nitro, toluenesulfonyl, trifluoroacetyl, benzyloxyformyl, etc. For example, the guanidine group of arginine can be protected with bis allyl carbonyl and finally removed using palladium catalysis.
Protecting carboxyl groups: Carboxyl groups in peptide chains may also need protection to prevent them from participating in unwanted reactions. For example, in the synthesis of ILE Glu (γ - pip), the amino group of ILE is protected by FMOC, while the carboxyl group of GLU is protected by TBU.
Protecting the chromophore: p-nitroaniline (the chromophore in PNA) has poor nucleophilicity due to the strong electron withdrawing effect of nitro groups, making it difficult to connect to amino acids through general amide condensation methods. In the present invention, the problem of connecting p-nitroaniline is solved by first connecting p-phenylenediamine to an amino acid and then oxidizing it. This method is more environmentally friendly, safe, and has a higher yield.