Synthesis of C-5 Substituted Tubercidin Derivatives.

Abstract

C-5 substituted pyrrolo(2,3-d)pyrimidine nucleosides are synthesized via reactions of 5-mercuritubercidin (2). Palladium catalyzed carbonylation of 2 in methanol gave 5-methoxycarbonyltubercidin (5) which could be converted to the nucleoside antibiotic sangivamycin (6) by reaction with ammonia. Reduction of 5 with LiBH4 in tetrahydrofuran gave 5-hydroxymethyltubercidin (7). Longer carbon chains were introduced by the palladium catalyzed coupling of olefins with mercuritubercidin. 5-Mercuritubercidin and methyl acrylate in 0.1 M Li2PdCl4 in methanol gave (E)-5-(2-methoxycarbonylethenyl) tubercidin (3) which on treatment with aqueous hydroxide was hydrolyzed to (E)-5-(2-carboxyethenyl) tubercidin (8). Nucleoside 8 was converted to (E)-5-(2-bromoethenyl)tubercidin 9 by N-bromosuccinimide in N.N-dimethylformamide. 3-Chloro-l-butene reacted with 2 and Li2PdCl4 to give a mixture of E and Z 5-(2-buten-l-yl) tubercidin (13,14). Styrene coupled with 2 to give 5-styryltubercidin 12. Finally the mercury could be replaced directly by iodine in DMF to give 5-iodotubercidin (15). Characterization of the C-5 substituted tubercidin derivatives by 13C NMR is discussed.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 1980
Accession Number
ADA126663

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  • Donald E. Bergstrom

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  • University of California

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  • Biomedical

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  • Alcohols
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  • Chemistry

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