Accelerated effect on Mitsunobu reaction via bis-N-tert-butoxycarbonylation protection of 2-amino-6-

• 作 者: Li-yan DAI Qiu-long SHI Jing ZHANG Xiao-zhong WANG Ying-qi CHEN
• 机 构: Department of Chemical and Biological Engineering, Zhejiang University,
• 出 处: Journal of Zhejiang University-Science A(Applied Physics & E
• 发表日期: 2013年10期
• 关键词: hydroxyethyl latter alcohols selectivity diacetate purine solubility derivative

Solubility of 2-amino-6-chloropurine in Mitsunobu solvents could be significantly improved after its exocyclic amino group is protected via N-tert-butoxycarbonylation.The bis-Boc protected 2-amino-6-chloropurine also shows excellent activity and N9 selectivity in the coupling with various alcohols by a Mitsunobu reaction.Then,a new practical and efficient method is established for the synthesis of penciclovir(PCV) from bis-Boc-2-amino-6-chloropurine 9 and the side chain of 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxane 5—the latter being a more easily prepared cyclic precursor of the diacetate side chain used in the conventional process.The coupling of 9 with 5 proceeded regioselectively at a N9 position of purine derivative for a good yield under Mitsunobu conditions.

Solubility of 2-amino-6-chloropurine in Mitsunobu solvents could be significantly improved after its exocyclic amino group is protected via N-tert-butoxycarbonylation. The bis-Boc protected 2-amino-6-chloropurine also shows excellent activity and N9 selectivity in the coupling with various alcohols by a Mitsunobu reaction. Chen, a new practical and efficient method is established for the synthesis of penciclovir (PCV) from bis-Boc-2-amino-6-chloropurine 9 and the side chain of 5- -hydroxyethyl) -2,2-dimethyl-1,3-dioxane 5-the latter being more likely prepared cyclic precursor of the diacetate side chain used in the conventional process. The coupling of 9 with 5 proceeded regioselectively at a N9 position of purine derivative for a good yield under Mitsunobu conditions.