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
N1 - Funding Information:
This work was supported in part by The Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan . We thank Prof. Osamu Kitagawa, Shibaura Institute of Technology, for the measurements of optical rotation.
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
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
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U2 - 10.1016/j.tet.2014.12.085
DO - 10.1016/j.tet.2014.12.085
M3 - Article
AN - SCOPUS:84921511582
SN - 0040-4020
VL - 71
SP - 1095
EP - 1100
JO - Tetrahedron
JF - Tetrahedron
IS - 7
ER -