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A facile route to synthesize N-(Boc-Aminoethylglycin)thymine Ethyl Ester, application to the synthesis of PNA-oligonucleotide conjugates

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Abstract

Peptide nucleic acid oligonucleotide conjugates are attracting immense interest currently because of their use in the biomedical and diagnostic field as antigene and molecular sensors. The efficient PNA synthesis methods can reduce their cost and may increase availability for their wider use. Here we described a facile synthesis of the peptide nucleic acid monomer N-(Boc-Aminoethylglycin)thymine Ethyl Ester [Ethyl 2-(N-(2-((tert-butoxycarbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetate]. The monomer N-(Boc-Aeg)thymine Ethyl Ester has been prepared in a good yield (96%) by highly efficient procedure involving direct coupling of nucleobase thymine with the backbone Ethyl N-(Boc-aminoethyl)-N-(chloroacetyl)glycinate, which was prepared from the reaction of Ethyl N-[(2-Boc-amino)-ethyl]glycinate with chlroacetylchloride. The key intermediate Ethyl N-[(2-Boc-amino)-ethyl]glycinate involved in the synthesis has been prepared via a scalable and cost-effective route with a yield of (98%). The thyminyl PNA monomer was reported to be used in various synthetic applications, and our cost-effective, highly scalable method of synthesis will expand its wider use.

Graphic abstract

A new method for the synthesis of Thymine-based PNA monomer precursor N-(Boc-Aeg)thymine Ethyl Ester in gram scale with high purity is reported here. In this method, the use of expensive coupling reagents is avoided.

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Acknowledgements

Authors are thankful to Dr. Chandra Shekhar Purohit (Associate Professor, SCS, NISER) for extending his research facilities for this work.

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Authors and Affiliations

  1. National Institute of Science Education and Research Bhubaneswar (HBNI), PO: Bhimpur-Padanpur, Jatni, Odisha, 752050, India

    Anuradha Das

  2. S. K. Dash Center of Excellence of Biosciences and Engineering and Technology, Indian Institute of Technology Bhubaneswar, Arugul, Jatni, Odisha, 752050, India

    Biswaranjan Pradhan

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  1. Anuradha Das
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  2. Biswaranjan Pradhan
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Correspondence to Anuradha Das.

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Das, A., Pradhan, B. A facile route to synthesize N-(Boc-Aminoethylglycin)thymine Ethyl Ester, application to the synthesis of PNA-oligonucleotide conjugates. J Chem Sci 132, 32 (2020). https://doi.org/10.1007/s12039-020-1738-y

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  • DOI: https://doi.org/10.1007/s12039-020-1738-y

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