A novel route to a chiral building block for the preparation of cyclopentenyl carbocyclic nucleosides. Synthesis and anticancer activity of enantiomeric neplanocins A. Issue 53 (27th August 2020)

• Record Type: Journal Article
• Authors: Łukasik, Beata; Mikina, Maciej; Mikołajczyk, Marian; Pawłowska, Róża; Żurawiński, Remigiusz
• Is Part Of: RSC advances. Volume 10:Issue 53(2020)
• Page Start: 31838
• Page End: 31847
• Publication Date: 2020-08-27
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra06394k
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A novel route to both enantiomers of a cyclopentene building block was developed and applied to the synthesis 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 .