New Modular and Efficient Approach to 6-Substituted Pyridin-2-yl C-Nucleosides

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• 作者：Milan Urban ; Radek Pohl ; Blanka Klepet&aacute ; //pubs.acs.org/images/entities/rcaron.gif" border="0">ov&aacute ; Michal Hocek
• 刊名：Journal of Organic Chemistry
• 出版年：2006
• 出版时间：September 15, 2006
• 年：2006
• 卷：71
• 期：19
• 页码：7322 - 7328
• 全文大小：141K
• 年卷期：v.71,no.19(September 15, 2006)
• ISSN：1520-6904

文摘

A novel modular, efficient, and practical methodology of preparation of 6-substituted pyridin-2-ylC-nucleosides was developed. An addition of 2-lithio-6-bromopyridine 2b to TBDMS-protected2-deoxyribonolactone 5 gave aduct 7 as an equilibrium mixture of anomeric hemiketals 1-(6-bromopyridin-2-yl)-1-hydroxynucleosides 7a,b and its open form 7c. Reduction of the adduct 7 with Et₃SiH andBF₃·Et₂O afforded the desired 6-bromonucleoside 8a as pure -anomer in a total yield of 32% overtwo steps from 5. Intermediate 8a was then subjected to a series of palladium catalyzed cross-couplingreactions and aminations to give a series of protected 1-(6-alkyl-, 6-aryl-, and 6-aminopyridin-2-yl)-2-deoxyribonucleosides 9. Catalytic hydrogenation of 8a gave an unsubstituted pyridine C-nucleoside,and diazotative oxodeamination of 6-aminopyridine nucleoside 9f by isopentyl nitrite in acetic acid gave6-oxopyridine nucleoside 10i. Deprotection of silylated nucleosides 9 by Et₃N·3HF gave a series of freeC-nucleosides 10.