Jump to main content
Jump to site search


Synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products

Author affiliations

Abstract

The present work deals with the synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products like physalins, with potential as antitumor agents. This synthetic methodology involves several key reactions: (a) synthesis of polyfunctionalized cycloheptenones by [4 + 3] cycloaddition reactions of furan precursors with oxyallyl cations; (b) Nicholas reaction with propargyl cations stabilized as dicobalt hexacarbonyl complexes; (c) demetallation and hydration of the resulting acetylenes; (d) stereoconvergent aldol cyclization to generate a key oxatricyclic intermediate and (e) a β-fragmentation process that affords, under hypoiodite photolysis, the desired product with moderate to good yield. The final compounds are the result of a radicalary β-fragmentation at the level of C2–C6 with respect to the tertiary hydroxyl group on C6, with an unexpected contraction from a ten- to a nine-membered ring system, via a radical addition to the carbonyl group on C4. The synthetic methodology has been scaled up to multigram level with good overall yield. Further biological, biochemical and biophysical studies are being carried out in our laboratory on these 1,7-epoxycyclononane derivatives to determine the potential of this kind of oxabicyclic compound as future hits and/or leads for the development of new anticancer drugs. The preliminary evaluation of the anticancer activity of the representative synthesized compounds, against the leukaemia cancer cell lines K-562 and SR, shows a promising activity with a GI50 = 0.01 μM and a LC50 = 7.4 μM for a conveniently functionalized 10-oxabicyclo[5.2.1]decane.

Graphical abstract: Synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products

Back to tab navigation

Supplementary files

Publication details

The article was received on 23 Jan 2018, accepted on 06 Feb 2018 and first published on 06 Feb 2018


Article type: Paper
DOI: 10.1039/C8OB00194D
Citation: Org. Biomol. Chem., 2018, Advance Article
  •   Request permissions

    Synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products

    Á. M. Montaña, S. Ponzano, M. Sanasi and G. Kociok-Köhn, Org. Biomol. Chem., 2018, Advance Article , DOI: 10.1039/C8OB00194D

Search articles by author

Spotlight

Advertisements