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Novel Synthesis of N-Glycosyl Amino Acids Using T3P®: Propylphosphonic Acid Cyclic Anhydride as Coupling Reagent

Abstract

In this paper is presented a novel and simple synthetic pathway for obtaining new protected and unprotected N-glucosyl amino acids from 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl amine and Fmoc-l-amino acids. Three methodologies were evaluated, using the coupling reagents: N,N,N′,N′-Tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate, diisopropylcarbodiimide and propylphosphonic acid cyclic anhydride. The obtained products using propylphosphonic acid cyclic anhydride showed less undesired species, easy purification and higher yields than the other two methodologies. Deprotection strategies widely used in solid phase peptide synthesis were applied to develop the synthetic pathway reported and achieve the final products. The protected and unprotected N-glucosyl amino acids were purified using solid phase extraction chromatography and characterized by high performance liquid Chromatography and nuclear magnetic resonance spectroscopy. Different amino acids (Fmoc-l-Asp(OtBu)OH, Fmoc-l-Phe(OH) and Fmoc-l-Lys(Boc)-OH) have been employed to demonstrate the simple and reproducible coupling methodology using propylphosphonic acid cyclic anhydride. The results showed that new protected and unprotected N-glucosyl amino acids can be obtained with high purity and the methodology could be used with any Fmoc-amino acid. The methodology developed could be considered as a synthetic tool for obtaining building blocks for glycopeptide synthesis and potential drugs candidates based on glycoconjugates.

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Acknowledgements

This research was conducted with the financial support of División de Investigación y Extensión sede Bogotá (DIEB), Universidad Nacional de Colombia through the Project code 34828 “Diseño y síntesis química de péptidos y glicoconjugados y evaluación de la actividad antibacteriana contra Escherichia coli ATCC 25922.”

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Correspondence to Javier Eduardo García Castañeda.

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Pinzón Martín, S.M., Medina, R.F., Iregui Castro, C.A. et al. Novel Synthesis of N-Glycosyl Amino Acids Using T3P®: Propylphosphonic Acid Cyclic Anhydride as Coupling Reagent. Int J Pept Res Ther 24, 291–298 (2018). https://doi.org/10.1007/s10989-017-9614-4

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Keywords

  • Glycoconjugate
  • N-glucosyl amino acids
  • Glycosidic bond
  • Propylphosphonic acid cyclic anhydride