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

Bulletin of the Korean chemical society

Hye Rim Kim¹  Ah-Young Park¹  Sujin Son¹  Pusoon Chun¹  Hwi Young Yun¹  Seong Jin Kim¹  Hyung Ryong Moon¹  Youngwoo Woo¹ 

关键词: 5-Methylbicyclo[3.1.0]hexanone;    Carbenoid cycloaddition;    3′-Ethenyl;    North conformation;    Mitsunobu reaction;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

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 (±)-7 with three contiguous chiral centers and its epimer (±)-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 (±)-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 (±)-11 with 6-chloropurine nucleobase afforded only the desired N9-alkylated nucleoside without the formation of N7-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.

【 授权许可】

Unknown