Synthesis and enantiomeric purity evaluation of a new small library of promising bioactive chiral derivatives of xanthones

For the last years, searching new chiral derivatives of xanthones (CDX) with potential pharmacological properties has remained in the area of interest of our group [1,2]. Recently, we have described the ability of CDX to inhibit the growth of different human tumor cell lines [1]. In fact, some of them exhibited interesting dose-dependent growth inhibitory effects on the evaluated cell lines being dependent on the stereochemistry.

Based on this work, herein we describe the synthesis of a new library of promising bioactive analogues, in enantiomerically pure form, with good yields, short reaction times and no racemization. The optimization of the synthetic pathways to obtain the xanthonic derivative used as chemical building block was also described.

The enantiomeric excesses for all synthesized CDX were measured by HPLC on (S,S)-Whelk-O1® chiral stationary phase under polar-organic elution conditions, achieving values higher than 99%.

The evaluation of growth inhibitory activity on human tumor cell lines of the synthesized CDX is in progress.

Acknowledgements:

This research was partially supported by the Strategic Funding UID/Multi/04423/2013 and UID/QUI/00062/2013 through national funds provided by FCT – Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020, and the Portuguese NMR Network.

References

[1] Fernandes C.; Masawang K.; Tiritan M. E.; Sousa E.; Lima V.; Afonso C.; Bousbaa H.; Sudprasert W.; Pedro M.; Pinto M. M. Bioorgan. Med. Chem. 2014, 22, 1049.

[2] Fernandes, C.; Oliveira, L.; Tiritan, M. E.; Leitao, L.; Pozzi, A.; Noronha-Matos, J. B.; Correia-de-Sá, P.; Pinto, M. M., Eur. J. Med. Chem., 2012, 55, 1.