Author:
Varga István,Goldschmidt Gőz Viktória,Pintér István,Csámpai Antal,Perczel András
Abstract
AbstractThe synthesis of d-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4–5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by 1H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized.
Funder
Beregi Fellowship sponsored by Servier Research Institute
Foundation for the Hungarian Peptide and Protein Research
ELTE Thematic Excellence Program
National Research, Development, and Innovation Fund of Hungary
European Union's Recovery and Resilience Instrument
Eötvös Loránd University
Publisher
Springer Science and Business Media LLC
Subject
Organic Chemistry,Clinical Biochemistry,Biochemistry
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