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http://dx.doi.org/10.5012/bkcs.2014.35.9.2649

Highly Efficient Synthesis of Conformationally Fixed Bicyclo[3.1.0]hexyl Nucleosides with an Ethenyl Group at C3'-Position as Potential Antiviral Agents  

Kim, Seong Jin (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Woo, Youngwoo (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Park, Ah-Young (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Kim, Hye Rim (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Son, Sujin (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Yun, Hwi Young (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Chun, Pusoon (College of Pharmacy, Inje University)
Moon, Hyung Ryong (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Publication Information
Abstract
Synthesis of north-5'-methylbicyclo[3.1.0]hexyl adenine and hypoxanthine nucleosides with an ethenyl group at C3' position was successfully achieved by a highly facile method. Methylbicyclo[3.1.0]hexanone (${\pm}$)-7 with three contiguous chiral centers and its epimer (${\pm}$)-6 was remarkably simply constructed only by four steps involving a carbenoid insertion reaction in the presence of rhodium (II) acetate dimer as a metal catalyst, giving a correct relative stereochemistry of the generated three chiral centers. Due to steric hindrance from the concave face of the bicyclo[3.1.0]hexanone system, a Grignard reaction of (${\pm}$)-7 with ethenylmagnesium bromide showed exclusive diastereoselectivity towards the b-face. The Grignard reaction chemoselectively proceeded without reacting with ester functionality. Coupling reaction of glycosyl donor (${\pm}$)-11 with 6-chloropurine nucleobase afforded only the desired $N^9$-alkylated nucleoside without the formation of $N^7$-regioisomer. By the conventional method, 6-chloro group was converted into 6-amino and 6-hydroxy groups to give the desired adenine and hypoxanthine bicyclo[3.1.0]hexyl carbanucleosides with 3'-ethenyl group, respectively.
Keywords
5-Methylbicyclo[3.1.0]hexanone; Carbenoid cycloaddition; 3'-Ethenyl; North conformation; Mitsunobu reaction;
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