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

• Published in: International journal of peptide research and therapeutics Vol. 24; no. 2; pp. 291 - 298
• Main Authors: Pinzón Martín, Sandra Milena, Medina, Ricardo Fierro, Iregui Castro, Carlos Arturo, Rivera Monroy, Zuly Jenny, García Castañeda, Javier Eduardo
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2018; Springer Nature B.V
• Subjects: Amino acids; Animal Anatomy; Biochemistry; Biomedical and Life Sciences; Chromatography; Drug development; Glycoconjugates; High-performance liquid chromatography; Histology; Life Sciences; Liquid chromatography; Magnetic resonance spectroscopy; Molecular Medicine; Morphology; NMR; Nuclear magnetic resonance; Peptide synthesis; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; Purification; Reagents; glucosyl amino acids; Glycosidic bond; Glycoconjugate; Propylphosphonic acid cyclic anhydride
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-017-9614-4

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.