Design, synthesis and cytotoxic evaluation of truncated 3′-deoxy- 3′, 3′ difluororibofuranosyl pyrimidine nucleosides. (November 2020)

• Record Type: Journal Article
• Authors: Sivakrishna, Balija; Shukla, Meenakshi; Santra, Manas Kumar; Pal, Shantanu
• Is Part Of: Carbohydrate research. Volume 497(2020)
• Publication Date: 2020-11
• Subjects: Truncated nucleoside -- Difluoropyrimidine nucleosides -- Oxidative cleavage -- Fluorination -- D-ribose; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2020.108113
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: Truncated 3 ′ -deoxy- 3 ′, 3 ′ difluororibofuranosyl pyrimidine nucleoside derivatives were synthesized from d -ribose via β -apioribo pyrimidine nucleoside intermediates 11a-c . The synthetic approach signifies that truncation at C3′ position of apioribose ring of 13a-c by oxidative cleavage of diols with Pb(OAc)4 and followed by fluorination with DAST as key steps. Cytotoxic evaluation of synthesized truncated nucleoside derivatives 16a-c and 19a-c were tested against MCF7 and MDA-MB-231 breast cancer cell lines. However, only 19a was shown minimal growth suppression activity on MDA-MB-231 cancer cell lines. Graphical abstract: Image 1 Highlights: Synthesis of truncated 3 ′ -deoxy- 3 ′, 3 ′ difluororibopyrimidine nucleosides from a commercially available starting material d -ribose. Formation of carbonyl group on ribofuranosyl nucleosides through simple oxidative diol cleavage by using Pb(OAc)4 and geminal fluorination with DAST afforded truncated difluororibo pyrimidine nucleosides. Cytotoxicity of all synthesized compounds were tested on MCF7 and MDA-MB-231 breast cancer cell lines.