Stereoselective synthesis of 1'-C-branched arabinofuranosyl nucleosides via anomeric radicals generated by 1,2-acyloxy migration.
Stereoselective C-C bond formation at the anomeric position of uracil and adenine nucleoside has been accomplished through reaction of the anomeric radical, generated by 1,2-acyloxy migration, with a radical acceptor. The present method consists of the following steps: (1) electrophilic addition (bromo-pivaloyloxylation) to 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-protected 1',2'-unsaturated nucleoside, (2) tin radical-mediated reaction of the resulting adduct with a radical acceptor. The use of allyl(tributyl)tin gave the 1'-C-allylated uracil nucleoside 14 in 66% yield together with the unrearranged 2'-C-allylated product 15 (6%). Radical acceptors such as styryl(tributyl)tin and 3-bromo-2-methylacrylonitrile can also be used in the reaction of 5, giving 16 (70%) and 17 (76%) without the formation of unrearranged product. The radical-mediated C-C bond formation of the adenine counterpart 12 was also investigated.
Haraguchi
Kazuhiro
K
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan harakazu@pharm.showa-u.ac.jp
Itoh
Yoshiharu
Y
Matsumoto
Kouichiro
K
Hashimoto
Kyoko
K
Nakamura
Kazuo T
KT
Tanaka
Hiromichi
H
D000225:Adenine / Q000737:chemistry; D002384:Catalysis; D007202:Indicators and Reagents; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014001:Tin / Q000737:chemistry; D014498:Uracil / Q000737:chemistry
D007202:Indicators and Reagents; D009705:Nucleosides; D009942:Organometallic Compounds; D014498:Uracil; D014001:Tin; D000225:Adenine