Synthesis Of Glucosyl Amino Acid Derivatives For Obtaining N-Glucopeptides Via Spps: Optimization Of The Synthetic Route

Building blocks of Fmoc-Asn-beta-(2,3,4,6-tetra-O-Acetyl-D-glucopyranosyl)-OH (5) Fmoc-Asn-beta-(2,3,4,6-tetra-O-Acetyl-D-mannopyranosyl)-OH (5 a), and Fmoc-Asn-beta-(2,3,4,6-tetra-O-Acetyl-D-galactopyranosyl)-OH (5 b) were synthesized from D-glucose, D-mannose, and D-galactose, respectively. The final products and their intermediates were characterized by means of NMR experiments. The synthetic route was optimized, and scaling to obtain 5 g of the Fmoc-Asn-beta-(2,3,4,6-tetra-O-Acetyl-D-glucopyranosyl)-OH significantly diminished the amount of solvents and reagents consumed, yielding a faster, cheaper and easy to implement process. The methodology developed allowed obtaining the building blocks with good yields and high purity with only one purification process. The Fmoc-Asn-beta-(2,3,4,6-tetra-O-Acetyl-D-glucopyranosyl)-OH building block (5) was used to synthetized N-glycopeptides derived from LfcinB. The results showed that the incorporation of the building block into the growing chain significantly affects the synthetic process using the SPPS (Solid Phase Peptide Synthesis) Fmoc/tBu strategy. It was established that the position of the building block in the sequence, as well the number of the building blocks incorporated, diminished the yields and purity of the final product. The methodologies reported could be used to synthetized building blocks containing monosaccharides and could contribute to improving N-glycopeptide synthesis.