Synthesis of novel pyrimidine apiothionucleosides and in vitro evaluation of their cytotoxicity

• Published in: Tetrahedron Vol. 71; no. 21; pp. 3396 - 3403
• Main Authors: Kotoulas, Stefanos S., Kojić, Vesna V., Bogdanović, Gordana M., Koumbis, Alexandros E.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 27.05.2015; Elsevier
• Subjects: Apiose; Chemistry; Chemistry, Organic; Cytotoxicity; Physical Sciences; Pummerer rearrangement; Pyrimidine base; Science & Technology; Thionucleosides; Pyrimidine base; Pummerer rearrangement; Apiose; Cytotoxicity; Thionucleosides; ANALOGS; NUCLEOSIDE; PUMMERER REACTION; PHARMACOLOGY; BIOLOGICAL EVALUATION; CHEMISTRY; CHEMICAL-SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; DERIVATIVES
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.03.089

A series of novel pyrimidine d- and l-apiothionucleosides were synthesized from l- and d-arabinose, respectively, following a common versatile and overall high-yielding scheme. The key-step was a regio- and stereo-selective Pummerer rearrangement reaction between a pyrimidine nucleobase and an appropriately functionalized thiosugar moiety. The role of the protecting group on the side hydroxymethyl group was studied in terms of productivity and selectivity of the reactions involved in the synthetic scheme. Evaluation of cytotoxic effects of the prepared compounds by MTT assay has shown that some of them exhibit potent antitumor activity (IC50 3–20 μM) against specific cancer cell lines, whereas none had an inhibitory effect on the normal cell line tested. [Display omitted]