C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies.
To obtain key sugar derivatives for making homooligomeric foldamers or α/β-chimera peptides, economic and multigram scale synthetic methods were to be developed. Though described in the literature, the cost-effective making of both 3-amino-3-deoxy-ribofuranuronic acid (H-t X-OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H-c X-OH) from D-glucose is described here. The present synthetic route elaborated is (1) appropriate for large-scale synthesis; (2) reagent costs reduced (e.g. by a factor of 400); (3) yields optimized are ~80% or higher for all six consecutive steps concluding -t X- or -c X- and (4) reaction times shortened. Thus, a new synthetic route step-by-step optimized for yield, cost, time and purification is given both for D-xylo and D-ribo-amino-furanuronic acids using sustainable chemistry (e.g. less chromatography with organic solvents; using continuous-flow reactor). Our study encompasses necessary building blocks (e.g. -X-OMe, -X-OiPr, -X-NHMe, Fmoc-X-OH) and key coupling reactions making -Aaa-t X-Aaa- or -Aaa-t X-t X-Aaa- type "inserts". Completed for both stereoisomers of X, including the newly synthesized Fmoc-c X-OH, producing longer oligomers for drug design and discovery is more of a reality than a wish.
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
Adrienn
A
Nagy
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
Barbara
B
Csordás
MTA-ELTE Protein Modelling Research Group, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
Virág
V
Zsoldos-Mády
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
István
I
Pintér
MTA-ELTE Protein Modelling Research Group, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
Viktor
V
Farkas
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. perczel@chem.elte.hu.|MTA-ELTE Protein Modelling Research Group, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. perczel@chem.elte.hu.
András
A
Perczel
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000606:Amino Sugars / Q000138:chemical synthesis*; D060326:Chemistry Techniques, Synthetic / Q000191:economics; D005947:Glucose / Q000737:chemistry; D013237:Stereoisomerism; D014574:Uronic Acids / Q000138:chemical synthesis*
D000596:Amino Acids; D000606:Amino Sugars; D014574:Uronic Acids; D005947:Glucose
Azido sugars; Foldamers; Nucleophilic substitution; Sugar amino acids