Amino Acids

, Volume 49, Issue 2, pp 223–240 | Cite as

C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies

  • Adrienn Nagy
  • Barbara Csordás
  • Virág Zsoldos-Mády
  • István Pintér
  • Viktor Farkas
  • András Perczel
Original Article

Abstract

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–tX–OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H–cX–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 –tX– or –cX– 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–tX–Aaa– or –Aaa–tXtX–Aaa– type “inserts”. Completed for both stereoisomers of X, including the newly synthesized Fmoc–cX–OH, producing longer oligomers for drug design and discovery is more of a reality than a wish.

Keywords

Sugar amino acids Azido sugars Nucleophilic substitution Foldamers 

Abbreviations

H-RibAFU(ip)-OH or tX

1,2-O-Isopropylidene-3-amino-3-deoxy-α-d-ribofuranuronic acid

H-XylAFU(ip)-OH or cX

1,2-O-Isopropylidene-3-amino-3-deoxy-α-d-xylofuranuronic acid

N3-RibAFU(ip)-OH

1,2-O-Isopropylidene-3-azido-3-deoxy-α-d-ribofuranuronic acid

N3-XylAFU(ip)-OH

1,2-O-Isopropylidene-3-azido-3-deoxy-α-d-xylofuranuronic acid

H-XylAFU(ip)-NHMe

N-Methyl-1,2-O-isopropylidene-3-amino-3-deoxy-α-d-xylofuranuronamide

H-RibAFU(ip)-NHMe

N-Methyl-1,2-O-isopropylidene-3-amino-3-deoxy-α-d-ribofuranuronamide

Ac-RibAFU(ip)-NHMe

N-Methyl-1,2-O-isopropylidene-3-acetamido-3-deoxy-α-d-ribofuranuronamide

Ac-XylAFU(ip)-NHMe

N-Methyl-1,2-O-isopropylidene-3-acetamido-3-deoxy-α-d-xylofuranuronamide

Supplementary material

726_2016_2346_MOESM1_ESM.docx (425 kb)
Supplementary material 1 (DOCX 425 kb)

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Adrienn Nagy
    • 1
  • Barbara Csordás
    • 1
  • Virág Zsoldos-Mády
    • 2
  • István Pintér
    • 1
  • Viktor Farkas
    • 2
  • András Perczel
    • 1
    • 2
  1. 1.Laboratory of Structural Chemistry and Biology, Institute of ChemistryEötvös Loránd UniversityBudapestHungary
  2. 2.MTA-ELTE Protein Modelling Research GroupBudapestHungary

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