Abstract
We have developed a new route for synthesizing mercapto C-nucleoside possessing a phenyl thiol group, using organometallic reagents. Duplexes incorporating redox-active nucleobase analogues display a high melting temperature under oxidation condition. Originally, we had anticipated the production of mercapto C-nucleoside using a Friedel-Crafts coupling reaction via bis(toluoyl) protected ribose and tert-butyl phenyl sulfide in the presence of Lewis acid. However, an undesired coupling compound was formed by cleavage of the S-tert-butyl group of S-tert-butyl phenyl sulfide by Lewis acids (BF3 Et2O, SnCl4). The highly stereoselective synthesis of mercapto C-nucleoside was, however, achieved by the addition of p-(tert-butyl)thiophenyllithium to a disiloxane-protected 2-deoxyribonolactone. This route showed moderately good yield at all steps. The tert-butyl moiety coupled to the sulfur atom at the phenyl group was converted to a 2-nitrophenylsulfenyl (Nps) group, and the Nps group was easily cleaved by ethanethiol to afford the desired compound and its disulfide dimer.
Original language | English |
---|---|
Pages (from-to) | 1095-1100 |
Number of pages | 6 |
Journal | Tetrahedron |
Volume | 71 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2015 Feb 18 |
Keywords
- C-nucleoside
- C-nucleoside
- Friedel-Crafts alkylation
- Lithiation
- Redox-active mercapto
- Stereoselective synthesis
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry