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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

Convenient and Efficient Syntheses of Peptide Nucleic Acid Purine Monomers

Author(s): Ahmed S. Abdelbaky*, Ivan A. Prokhorov, Elena V. Gnuskova, Olga V. Esipova and Yulia G. Kirillova

Volume 23, Issue 19, 2019

Page: [2122 - 2130] Pages: 9

DOI: 10.2174/1385272823666191014161442

Price: $65

Abstract

Currently, peptide nucleic acids (PNAs) play an important role as therapeutic agents, molecular tools for diagnosis and detection of genetic diseases as well as in biosensor probes. This research aims to optimize the synthesis of aeg- and γ-(S)-Me PNA monomers based on L-Ala, intended for oligomerization according to the Boc protocol. The monomers were obtained through the condensation of the corresponding pseudopeptides with carboxymethyl purine nucleic bases. During the work, the optimization of benzyloxycarbonyl- N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-ylacetic acid was carried out. The synthesis of benzyloxycarbonyl-N6-adenine-9-yl-acetic acid was conducted in three stages based on adenine with an overall yield of 22%. At the same time, the conditions for effective recrystallization of the mixture after alkylation of benzyloxycarbonyl-N6-adenine with ethyl bromoacetic acid ether have been developed to isolate the desired N9-regioisomer. Also, the optimization of a known method for producing benzyloxycarbonyl-N2-guanine-9-ylacetic acid from 2-amino-6-chloropurine was carried out. The total yield of the five-stage scheme was 55%. Condensation of aeg- and γ-(S)-Me pseudopeptides with benzyloxycarbonyl-N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-yl-acetic acid was performed by the standard carbodiimide method, DCC/HOBt in DMF followed by the removal of C-terminal methyl protective group by alkaline hydrolysis. The structure of the new compounds obtained was confirmed by spectral analysis methods. This work provides simple and optimized methods for obtaining protected carboxymethyl purine bases and increasing the efficiency of the synthesis and synthesized purine PNA monomers in an acceptable yield.

Keywords: aeg-PNA, γ-PNA, carboxymethyl-nucleobases, adenine, guanine, benzyloxycarbonyl protective group, PNA monomers.

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