Amino Acids

, Volume 48, Issue 11, pp 2619–2633

Origin of problems related to Staudinger reduction in carbopeptoid syntheses

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

DOI: 10.1007/s00726-016-2289-x

Cite this article as:
Csordás, B., Nagy, A., Harmat, V. et al. Amino Acids (2016) 48: 2619. doi:10.1007/s00726-016-2289-x
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Abstract

We report the solid phase synthesis of –GG-X-GG– type α/β-carbopeptoids incorporating RibAFU(ip) (1a, tX) or XylAFU(ip) (2a, cX) sugar amino acids. Though coupling efficacy is moderate, both the lengthier synthetic route using Fmoc derivative (e.g., Fmoc-RibAFU(ip)-OH) and the azido derivative (e.g., N3-RibAFU(ip)-OH) via Staudinger reaction with nBu3P can be successfully applied. Both X-ray diffraction, 1H- and 31P-NMR, and theoretical (QM) data support and explain why the application of Ph3P as Staudinger reagent is “ineffective” in the case of a cis stereoisomer, if cX is attached to the preceding residue with a peptide (–CONH–) bond. The failure of the polypeptide chain elongation with N3-cX originates from the “coincidence” of a steric crowdedness and an electronic effect disabling the mandatory nucleophilic attack during the hydrolysis of a quasi penta-coordinated triphenylphosphinimine. Nevertheless, the synthesis of the above α/β-chimera peptides as completed now by a new pathway via 1,2-O-isopropylidene-3-azido-3-deoxy-ribo- and -xylo-furanuronic acid (H-RibAFU(ip)-OH 1a and H-XylAFU(ip)-OH 2a) coupled with N-protected α-amino acids on solid phase could serve as useful examples and starting points of further synthetic efforts.

Keywords

CarbopeptoidsStaudinger reactionSugar amino acidsIminophosphorane

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-RibAFU(ip)-NHMe

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

H-XylAFU(ip)-NHMe

N-methyl-1,2-O-isopropylidene-3-amino-3-deoxy-α-D-xylofuranuronamide

H-XylAFU(ip)-NHMe2

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

Supplementary material

726_2016_2289_MOESM1_ESM.docx (152 kb)
Supplementary material 1 (DOCX 152 kb)

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Barbara Csordás
    • 1
  • Adrienn Nagy
    • 1
  • Veronika Harmat
    • 1
  • Virág Zsoldos-Mády
    • 2
  • Ibolya Leveles
    • 3
  • 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
  3. 3.BME Department of Applied Biotechnology and Food ScienceBudapestHungary