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

Objective

• 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

• D. Gembarovski et al, J. Pharm. Biomed. Anal. 86 (2013) 1–10
• M. Matanovic Skugor at al, Bioorg. Med. Chem. 18 (2010) 6547–6558
• Z. Marusic Istuk et al, Bioorg. Med. Chem. 19 (2011) 556–566
• M. Bukvic Krajacic et al, Eur. J. Med. Chem 52 (2007) 138–145
• Pesic et al, Eur. J. Med. Chem 49 (2012) 365-378