Synthesis of C-5 Substituted Tubercidin Derivatives.
Annual rept. Feb 79-Jan 80,
CALIFORNIA UNIV DAVIS
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C-5 substituted pyrrolo2,3-dpyrimidine 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-bromoethenyltubercidin 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.