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

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.