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Concise Synthesis of 4'-Modified Thymidines via 1,5-Hydrogen Atom Transfer/Intermolecular 1,4-Addition Process
Yuta Ito1, Kang Juri1, Yasufumi Fuchi1
1Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima 770-8514, Japan.
Abstract:
A concise approach is presented for preparing 4'-modified thymidines from oxime imidates using readily generated 4'-carbon radicals. This method produces 4'-modified thymidines from natural thymidine using the Mitsunobu reaction, the protection of 3'-hydroxy group (when necessary), and 1,5-hydrogen atom transfer (1,5-HAT)/intermolecular 1,4-addition with electron-deficient olefins. Moreover, using a one-pot synthesis involving 1,5-HAT/intermolecular 1,4-addition, followed by the hydrolysis of the imidate intermediate under basic conditions, 4'-modified thymidine was diastereoselectively isolated. This is because the 4'-isomer transferred to the water layer in the work-up process.
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