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Fragmentation Study Using H/D Exchange and ESI-MSn to Facilitate Structural Elucidation of Novel Macrocycles

Objective

  • Detailed fragmentation study of azithromycin aglycone and its derivatives by means of ESI-MSn and H/D exchange – detailed understanding of fragmentation pathways of different 15-membered azalides
  • H/D exchange  experiments - insight into fragmentation routes of analysed compounds
  • Comparison of fragmentation patterns of macrocyclic [M+H]+ ions and sodium adduct ions [M+Na]+ -influence of an alkali metal interacting with the aglycone ring on the product-ion spectra

  • The synthesis of new macrolide antibiotics involving structural modifications of azithromycin leads to novel classes of compounds. New chemical series were based on an aglycone ring as a core structure.
  • Understanding the fragmentation of the different structural modifications of 15-membered azalides enables easier structure elucidations of newly synthesised compounds, proces impurities, related substances and degradation products.
  • Comprehensive fragmentation study on azithromycin and it’s analogues using ESI-MSn and H/D exchange on both [M+H]+ and [M+Na]+ gave insight characteristic fragments.

  • Characteristic elimination of sugars from azithromycin in deuterated solvent gave ions at m/z 596, 597 and 598.
  • The most intense signal at m/z 596 corresponded to the elimination of cladinose sugar moiety.
  • The elimination of desosamine sugar from compound azithromycin gave two ions with signals at m/z 597 and m/z 598.
  • Possible structures representing the elimination of sugars from azithromycin in deuterated solvent are given in scheme.

References

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