Synthesis Of Benzouracils-A New Style Monomers Of Peptide Nucleic Acids

Peptide nucleic acid (PNA) is a synthesized analogue of DNA/RNA in which the sugar-phosphate backbone is replaced by achiral N-(2-aminoethyl)-glycyl backbone. This backbone consists of repeating units of aminoethylglycine with the nucleobases attached via a methylene carbonyl linker. Although its backbone structure is completely different from that of natural nucleic acids, PNA has high binding affinity and specificity for the complementary single strands of DNA and RNA sequences based on the Watson-Crick and Hoogsteen basepairing rules partially because of the absence of electrostatic repulsion between the neutral molecule of PNA and the polyanionic target DNA and RNA. In addition, PNA can be synthesized in relatively large quantities employing conventional solid phase peptide synthetic technology. For these reasons, PNA is a very interesting and potentially useful tool in molecular biology, and may have both diagnostic and therapeutic applications, which make them useful for antisense and antigene therapies.However there are still some limitations for the use of PNA in diagnostic and research applications, for example the low solubility in water, the tendency towards self-aggregation and the poor cell permeability, so great numbers of new PNA with various modifications both in backbone and in nucleobases were synthesized in order to circumvent these drawbacks and to optimize the properties of PNA.Thymine and uracil are important nucleobases in biology, being responsible for a wide range of biochemical processes, such as complementary base pairing in genetic information storage and transfer, molecular recognition. Therefore, considerable efforts have been made to investigate thymine, uracil and their derivatives. Seven novel class of PNA monomers, which are derivatives of thymine, uracil, have been designed and prepared in order to overcome the the limitations for the use of PNA in our group, especially, we discover a new, facile, and one-pot synthetic route to synthesis the derivatives of nucleobases, which meet the requirement of green chemistry. We also tend to provide the mechanism for the reaction. All products characterized by 1H NMR,13C NMR, MS spectra. The new PNA monomers are promising to solve the limitations for the use of PNA to be incorporated into PNA oligomers, including bis-PNAs to evaluate their base-pairing properties in PNA-DNA, PNA-RNA, and PNA-PNA duplexes.