Structural Chemistry

, Volume 23, Issue 6, pp 1785–1796

Synthesis, NMR and X-ray structure analysis of macrolide aglycons

  • Irena Ćaleta
  • Ana Čikoš
  • Dinko Žiher
  • Ivica Đilović
  • Marko Dukši
  • Dubravka Gembarovski
  • Ivan Grgičević
  • Mirjana Bukvić Krajačić
  • Darko Filić
  • Dubravka Matković-Čalogović
  • Ivica Malnar
  • Sulejman Alihodžić
Original Research

Abstract

Macrolide aglycons (E)-9-hydroxyimino-6-O-methylerythronolide A (4), 9a-aza-9-deoxo-9,9-dihydro-9a,11-O-dimethyl-9a-homoerythronolide A (5) and 9a-aza-9-deoxo-9,9-dihydro-9a-homoerythronolide A (6) were prepared by multistep syntheses. A conformational study of these new macrolide aglycons was performed using single crystal X-ray crystallography to gain information about the solid state, while a combination of NMR spectroscopy and molecular modelling was employed to study the solution structures. The crystal structures were found to be stabilised by a complex network of hydrogen bonds and van der Waals interactions. To some extent, the same building motif of infinite molecular chains held together by O–H···O hydrogen bonds was present in the crystal structure of all three compounds. Thorough analysis and comparison of the obtained solid state structures with their solution counterparts showed no significant differences between them, confirming the constrained flexibility of the macrocyclic ring. Moreover, in all three compounds, in both solution and solid state, the macrolactone ring adopts energetically more favoured folded-out conformations.

Keywords

Macrolide Aglycon NMR MS Single crystal X-ray analysis Structure analysis 

Supplementary material

11224_2012_9984_MOESM1_ESM.docx (85 kb)
Supplementary material (DOCX 85 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Irena Ćaleta
    • 1
    • 3
  • Ana Čikoš
    • 1
    • 3
  • Dinko Žiher
    • 1
    • 3
  • Ivica Đilović
    • 2
  • Marko Dukši
    • 1
    • 3
  • Dubravka Gembarovski
    • 1
    • 3
  • Ivan Grgičević
    • 1
    • 3
  • Mirjana Bukvić Krajačić
    • 1
    • 3
  • Darko Filić
    • 1
    • 3
  • Dubravka Matković-Čalogović
    • 2
  • Ivica Malnar
    • 1
    • 3
  • Sulejman Alihodžić
    • 1
    • 3
  1. 1.GlaxoSmithKline Research Centre Zagreb LtdZagrebCroatia
  2. 2.Department of Chemistry, Faculty of ScienceUniversity of ZagrebZagrebCroatia
  3. 3.Galapagos Research Center LtdZagrebCroatia

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