Abstract
The first examples of chemical modification of antibiotic oligomycin A are described. The interaction of oligomycin A with hydroxylamine yielded six-membered nitrone annelated with the antibiotic at the positions 3,4,5,6,7. The reaction with 1-aminopyridinium iodide in pyridine led to pyrazolo[1,5-a]pyridine conjugated with the antibiotic at the positions 2 and 3 (product of addition to the C2–C3 double bond followed by spontaneous oxidation). The structures of the compounds obtained were supported by NMR and mass spectrometry methods including the 15N-labeling of compounds.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Wender, P. A. et al. Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues. Org. Lett. 8, 589–592 (2006).
Smith, R. M., Peterson, W. H. & McCoy, E. Oligomycin, a new antifungal antibiotic. Antibiot. Chemother. 4, 962 (1954).
Salomon, A. R., Voehringer, D. W., Herzenberg, L. A. & Khosla, C. Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F0F1-ATPase. Proc. Natl Acad. Sci. USA 97, 14766–14771 (2000).
Alekseeva, M. G., Elizarov, S. M., Bekker, O. B., Lubimova, I. K. & Danilenko, V. N. F0F1ATP synthase of streptomycetes: modulation of activity and oligomycin resistance by protein Ser/Thr kinases. Biologicheskie Membrany (Rus) 26, 41–49 (2009).
Kim, B. S., Surk Sik Moon, S. S. & Hwang, B. K. Isolation, identification, and antifungal activity of a macrolide antibiotic, oligomycin A, produced by Streptomyces libani. Can. J. Bot. 77, 850–858 (1999).
Kobayashi, K. et al. Oligomycin E, a new antitumor antibiotic produced by Streptomyces sp. MCI-2225. J. Antibiot. 40, 1053–1057 (1987).
Li, Y. C. et al. Mitochondria-Targeting Drug Oligomycin Blocked P-Glycoprotein Activity and Triggered Apoptosis in Doxorubicin-Resistant HepG2 Cells. Chemotherapy. 50, 55–62 (2004).
Laatsch, H. et al. Oligomycin F, a new immunosuppressive homologue of oligomycin A. J. Antibiot. 46, 1334–1341 (1993).
Yamazaki, M. et al. 44-Homooligomycins A and B, new antitumor antibiotics from Streptomyces bottropensis. Producing organism, fermentation, isolation, structure elucidation and biological properties. J. Antibiot. 45, 171–179 (1992).
Thomas, D. I., Cove, J. H., Baumberg, S., Jones, C. A. & Rudd, B. A. Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide. J. Gen. Microbiol. 137, 2331–2337 (1991).
Panek, J. S. & Jain, N. F. J. Total Synthesis of Rutamycin B and Oligomycin C. Org. Chem. 66, 2747–2756 (2001).
Wagenaar, M. M., Williamson, R. T., Ho, D. M. & Carter, G. T. Structure and absolute stereochemistry of 21-hydroxyoligomycin A. J. Nat. Prod. 70, 367–371 (2007).
Szilagyi, L. & Feher, K. Oligomycins B and C: complete ab initio assignments of their 1H and 13C spectra and a study of their conformations in solution. J. Mol. Structure 471, 195–207 (1998).
Carter, G. T. Structure determination of oligomycin A and C. J. Org. Chem. 51, 4264–4271 (1986).
Herczegh, P. et al. Cycloaddition reactions of carbohydrate derivatives. Part IV. Synthesis of a tetrahydroxyindolizidine through a cyclic nitrone prepared from D-xylose. Tetrahedron Lett. 34, 1211–1214 (1993).
Grigor'ev, I. Nitrones: novel strategies in synthesis. in Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis. Novel Strategies in Synthesis (ed. Feuer H) 129 (John Wiley & Sons Inc., Hoboken, USA, 2008).
Heaney, F. & O'Mahoney, C. J. The influence of oxime stereochemistry in the generation of nitrones from ω-alkyloximes by cyclization or 1,2-prototropy. Chem. Soc. Perkin Trans. 1, 341–349 (1998).
Mason, J. in ‘Multinuclear NMR’ (ed. Mason, J.) 359 (Plenum Press, NY, 1987).
Harju, K. et al. Solid-phase synthesis of pyrazolopyridines from polymer-bound alkyne and azomethyne imines. J. Comb. Chem. 8, 344–349 (2006).
Tominaga, Y., Hidaki, S., Matsuda, Y. & Kobayashi, G. Reaction of pyridinium and quinolinium N-imines with ketenethioacetals. Yakugaku Zasshi 104, 440–448 (1984).
Gösl, R. & Meuwsen, A. 1-Aminopyrydinium Iodide. Organic Synthesis 43, 1–3 (1963).
Acknowledgements
This work was supported by the program ‘Research and development in the priority directions of development îf scientific-technological complex of Russia in 2007–2012’, contract no. 02.512.12.2056, 2009 ‘Development and validation of test systems for screening of oligomycin A derivatives’. We are grateful to Alexey S Trenin (Gause Institute of New Antibiotics) for the investigation of antifungal properties of our compounds.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lysenkova, L., Turchin, K., Danilenko, V. et al. The first examples of chemical modification of oligomycin A. J Antibiot 63, 17–22 (2010). https://doi.org/10.1038/ja.2009.112
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ja.2009.112
Keywords
This article is cited by
-
Study on retroaldol degradation products of antibiotic oligomycin A
The Journal of Antibiotics (2014)
-
A novel acyclic oligomycin A derivative formed via retro-aldol rearrangement of oligomycin A
The Journal of Antibiotics (2012)
-
Synthesis and properties of a novel brominated oligomycin A derivative
The Journal of Antibiotics (2012)
-
Generation of reduced macrolide analogs by regio-specific biotransformation
The Journal of Antibiotics (2011)
