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Efficient synthesis of exo-N-carbamoyl nucleosides: application to the synthesis of phosphoramidate prodrugs.

ABSTRACT: An efficient protection protocol for the 6-exo-amino group of purine nucleosides with various chloroformates was developed utilizing N-methylimidazole (NMI). The reaction of an exo-N(6)-group of adenosine analogue 1 with alkyl/and aryl chloroformates under optimized conditions provided the N(6)-carbamoyl adenosines (2a-j) in good to excellent yields. The reaction of N(6)-Cbz-protected nucleosides (5a-c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afforded the corresponding phosphoramidate pronucleotides (8a-c) in excellent yield.

SUBMITTER: Cho JH

PROVIDER: S-EPMC3432299 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Efficient synthesis of exo-N-carbamoyl nucleosides: application to the synthesis of phosphoramidate prodrugs.

Cho Jong Hyun JH Coats Steven J SJ Schinazi Raymond F RF

Organic letters 20120503 10

An efficient protection protocol for the 6-exo-amino group of purine nucleosides with various chloroformates was developed utilizing N-methylimidazole (NMI). The reaction of an exo-N(6)-group of adenosine analogue 1 with alkyl/and aryl chloroformates under optimized conditions provided the N(6)-carbamoyl adenosines (2a-j) in good to excellent yields. The reaction of N(6)-Cbz-protected nucleosides (5a-c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afford ...[more]

PMID: 22554490

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