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 |
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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 journal › Article
}
TY - JOUR
T1 - Improved synthesis of mercapto C-nucleoside possessing p-phenyl thiol as base using a lithiated coupling reaction
AU - Hatano, Akihiko
AU - Okada, Munehiro
AU - Dezaki, Kentaro
AU - Hirai, Seitaro
PY - 2015/2/18
Y1 - 2015/2/18
N2 - 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.
AB - 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.
KW - C-nucleoside
KW - C-nucleoside
KW - Friedel-Crafts alkylation
KW - Lithiation
KW - Redox-active mercapto
KW - Stereoselective synthesis
UR - http://www.scopus.com/inward/record.url?scp=84921511582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921511582&partnerID=8YFLogxK
U2 - 10.1016/j.tet.2014.12.085
DO - 10.1016/j.tet.2014.12.085
M3 - Article
AN - SCOPUS:84921511582
VL - 71
SP - 1095
EP - 1100
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 7
ER -