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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

Abstract: 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.

Key words: 2-amino-6-chloropurine, Mitsunobu reaction, bis-Boc protection, Penciclovir (PCV)


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DOI:

10.1631/jzus.A1300238

CLC number:

X5

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On-line Access:

2013-10-07

Received:

2013-07-10

Revision Accepted:

2013-09-03

Crosschecked:

2013-09-12

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