Participation of sulfur occurred during the Mitsunobu reaction: synthesis of novel isodideoxythionucleosides

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Lak Shin Jeong, Su Jeong Yoo, Hyung Ryong Moon, Yun Ha Kim and Moon Woo Chun


Abstract

Novel isodideoxythionucleosides have been synthesized from our versatile intermediate, L-4-thioarabitol derivative 5 using the Mitsunobu reaction as a key step. It is found that the sulfur atom of the 4-thiofuranose derivative takes part in the Mitsunobu reaction.


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  10. To a solution of triphenylphosphine (1.5 mol) in dry THF was added dropwise diethyl azodicarboxylate (DEAD, 1.5 mol) at 0 °C and the reaction mixture was stirred at room temperature for 2 h. To this mixture was added a solution of benzoic acid (1.5 mol) in THF followed by a solution of 9(1.0 mol) in dry THF and the reaction mixture was stirred at 60 °C for 8 h. More triphenylphosphine (1.5 mol), DEAD (1.5 mol) and benzoic acid (1.5 mol) were added to the mixture at room temperature and the mixture was stirred at 60 °C for 15 h. Since starting material 9 still remained on TLC, more triphenylphosphine (1.5 mol), DEAD (1.5 mol) and benzoic acid (1.5 mol) were again added to the mixture at room temperature and the mixture was further stirred at 60 °C for 6 h. The mixture was evaporated and the residue was purified by silica gel column chromatography (hexanes–ethyl acetate 15:1) to give 11a(85%) and 11b(15%).
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