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Synthesis 2003(13): 1989-1994
DOI: 10.1055/s-2003-41039
DOI: 10.1055/s-2003-41039
PAPER
© Georg Thieme Verlag Stuttgart · New York
Synthesis of Dinucleotide Thiophosphoramidates as Anti-HIV New Prodrugs
Further Information
Received
6 May 2003
Publication Date:
28 August 2003 (online)
Publication History
Publication Date:
28 August 2003 (online)
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Abstract
Sequential transesterification of diphenyl phosphite with 5′-O-(4,4′-dimethoxytrityl)thymidine (1) and hydrogen sulfide gave O-[5′-O-(4,4′-dimethoxytrityl)thymidine-3′-yl] H-thiophosphonate (2), and subsequent condensation of 2 with AZT or d4T in the presence of diphenyl chlorophosphoate provided the dinucleotide H-thiophosphonates 3 or 3′. The Antherton-Todd reaction of 3 or 3′ with l-amino acid methyl ester in a solution of CCl4-Et3N-H2O-MeCN gave the dinuleotide thiophosphoramidates 4 or 4′, and removal of the dimethoxytrityl protecting group in formic acid yielded the target products AZT/d4T thiophosphoramidates 5 and 5′.
Key words
nucleotides - phosphorus - antiviral agents - esterification - drugs
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