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

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...

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Published inJournal of Zhejiang University. A. Science Vol. 14; no. 10; pp. 760 - 766
Main Authors Dai, Li-yan, Shi, Qiu-long, Zhang, Jing, Wang, Xiao-zhong, Chen, Ying-qi
Format Journal Article
LanguageEnglish
Published Hangzhou Zhejiang University Press 01.10.2013
Subjects
Chains
Civil Engineering
Classical and Continuum Physics
Derivatives
Engineering
Industrial Chemistry/Chemical Engineering
Joining
Mechanical Engineering
Precursors
Purines
Solubility
Solvents
Synthesis
bis-Boc protection
Penciclovir (PCV)
X5
Mitsunobu reaction
2-amino-6-chloropurine
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Summary: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-l,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.
Bibliography:2-amino-6-chloropurine, Mitsunobu reaction, bis-Boc protection, Penciclovir （PCV）
Li-yan DAI, Qiu-long SHI, Jing ZHANG, Xiao-zhong WANG, Ying-qi CHEN （Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China）
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-l,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.
33-1236/O4
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1673-565X
1862-1775
DOI:10.1631/jzus.A1300238