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A computational approach to the synthesis of dirithromycin

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Abstract

Dirithromycin is a macrolide antibiotic derived from erythromycin A. Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the condensation mechanism has been analyzed computationally by the AM1 method in the gas phase. First, the formation of the Schiff bases of dirithromycin and epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and epidirithromycin were considered. Finally, the epimerization of the Schiff base of epidirithromycin to the Schiff base of dirithromycin was investigated. Our results show that, even though carbinolamine forms faster for epidirithromycin than the corresponding structure for dirithromycin, dirithromycin is the major product of the synthesis.

Figure Synthesis of dirithromycin

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Acknowledgements

The authors would like to thank Boğaziçi Araştırma Fonu project 01M101 and TUBITAK (The Scientific and Technical Research Council of Turkey) Münir Birsel Foundation for financial support. The authors would also like to thank Dr. Nurcan Tüzün, Aliment Özen and Cem Öztürk for their efforts to support this project.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Art and Sciences, Boğaziçi University, Bebek, 34342, Istanbul, Turkey

    Dilek Duran & Viktorya Aviyente

  2. Laboratory of Computational Biology, Faculty of Engineering and Natural Sciences, Sabanci University, Orhanlı, Tuzla, 34956, Istanbul, Turkey

    Canan Baysal

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  1. Dilek Duran
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  2. Viktorya Aviyente
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  3. Canan Baysal
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Correspondence to Viktorya Aviyente.

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Duran, D., Aviyente, V. & Baysal, C. A computational approach to the synthesis of dirithromycin. J Mol Model 10, 94–101 (2004). https://doi.org/10.1007/s00894-003-0172-7

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  • DOI: https://doi.org/10.1007/s00894-003-0172-7

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