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Stereoselective synthesis of 2'-beta-carbon-substituted 2'-deoxy-4'-thioribonucleosides from 4-thiofuranoid glycal
Kazuhiro Haraguchi1, Noriaki Shiina, Yuichi Yoshimura
1School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Abstract:
The 4-thiofuranoid glycal 6 was converted into 1-chlorinated derivative 7 through LDA lithiation. When 7 was treated with LTMP, successful C-2 lithiation occurred, and subsequent treatment of the lithiated species with MeI gave 8. Dechlorination of 8 with Na/liq.NH3 yielded the 2-methyl glycal 9. Glycosidation of 9 with silylated thymine was mediated with PhSeCl as an electrophile, and gave the beta-isomer 10 stereoselectively. Removal of the 2'-phenylselenenyl group of 10 was effected with tributyltin radical, and subsequent deprotection furnished the target 2'-beta-methyl 4'-thiothymidine (11). In a similar manner, the corresponding cytosine analogue 12 could also be synthesized.
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