Accelerated effect on Mitsunobu reaction via bis-N-tert-butoxycarbonylation protection of 2-amino-6-chloropurine and its application in a novel synthesis of penciclovir

作者：Dai, Li-yan^*; Shi, Qiu-long; Zhang, Jing; Wang, Xiao-zhong; Chen, Ying-qi

来源：Journal of Zhejiang University-Science A(Applied Physics & Engineering), 2013, 14(10): 760-766.

DOI：10.1631/jzus.A1300238

• 2-amino-6-chloropurine
• Mitsunobu reaction
• bis-Boc protection
• Penciclovir (PCV)

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.

• 出版日期2013-10
• 单位浙江大学