The synthesis of both enantiomers of 3-[(-butyldimethylsilyl)oxy]methyl-4,5--isopropylidenecyclopent-2-en-1-ol was accomplished in six steps based on optically inactive dimethyl -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 IC 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.
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| http://dx.doi.org/10.1039/d0ra06394k | DOI Listing |
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