Improved synthesis of mercapto C-nucleoside possessing p-phenyl thiol as base using a lithiated coupling reaction

Akihiko Hatano, Munehiro Okada, Kentaro Dezaki, Seitaro Hirai

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1095-1100
Number of pages6
JournalTetrahedron
Volume71
Issue number7
DOIs
Publication statusPublished - 2015 Feb 18

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Nucleosides
Sulfhydryl Compounds
Lewis Acids
Sulfides
Ribose
Organometallics
Sulfur
Disulfides
Dimers
Melting point
Atoms
Oxidation

Keywords

  • C-nucleoside
  • C-nucleoside
  • Friedel-Crafts alkylation
  • Lithiation
  • Redox-active mercapto
  • Stereoselective synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Improved synthesis of mercapto C-nucleoside possessing p-phenyl thiol as base using a lithiated coupling reaction. / Hatano, Akihiko; Okada, Munehiro; Dezaki, Kentaro; Hirai, Seitaro.

In: Tetrahedron, Vol. 71, No. 7, 18.02.2015, p. 1095-1100.

Research output: Contribution to journalArticle

Hatano, Akihiko ; Okada, Munehiro ; Dezaki, Kentaro ; Hirai, Seitaro. / Improved synthesis of mercapto C-nucleoside possessing p-phenyl thiol as base using a lithiated coupling reaction. In: Tetrahedron. 2015 ; Vol. 71, No. 7. pp. 1095-1100.
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