A novel route to a chiral building block for the preparation of cyclopentenyl carbocyclic nucleosides. Synthesis and anticancer activity of enantiomeric neplanocins A

Beata Łukasik; Maciej Mikina; Marian Mikołajczyk; Róża Pawłowska; Remigiusz Żurawiński

doi:10.1039/d0ra06394k

A novel route to a chiral building block for the preparation of cyclopentenyl carbocyclic nucleosides. Synthesis and anticancer activity of enantiomeric neplanocins A

RSC Adv. 2020 Aug 27;10(53):31838-31847. doi: 10.1039/d0ra06394k. eCollection 2020 Aug 26.

Authors

Beata Łukasik¹, Maciej Mikina¹, Marian Mikołajczyk¹, Róża Pawłowska², Remigiusz Żurawiński¹

Affiliations

¹ Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences Sienkiewicza 112 90-363 Łódź Poland remzur@cbmm.lodz.pl +48-426803260.
² Division of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences Sienkiewicza 112 90-363 Łódź Poland.

Abstract

The synthesis of both enantiomers of 3-[(tert-butyldimethylsilyl)oxy]methyl-4,5-O-isopropylidenecyclopent-2-en-1-ol was accomplished in six steps based on optically inactive dimethyl meso-tartrate. This key intermediate in the synthesis of cyclopentenyl carbocyclic nucleosides was subsequently applied in the preparation of enantiomeric neplanocins A. The toxic effect of these compounds was investigated for a series of suspension and adherent cancer cell lines and normal human fibroblasts. (-)-Neplanocin A ((-)-NPA) was more toxic against all tested cancer cell lines than its dextrorotary counterpart. The highest toxicity with IC₅₀ values of 7 and 10 μM was observed for the MOLT-4 and A431 cells, respectively. Moreover, (-)-NPA also induced apoptosis in A431 cell while this effect was not observed for (+)-NPA.