Novel ring transformation of 5-(2,3,5-tri-O-benzoyl-β-d-ribofuranosyl)isoxazole-4-carbaldehyde with 1,2-diaminobenzenes to 3-cyano-1,5-benzodiazepine C-nucleosides

Syntheses of 3-cyano-7- and 8-substituted-4-(β-d-ribofuranosyl)-1H-1,5-benzodiazepines were reported. Treatment of isoxazole carbaldehyde with 1,2-diamino-4-nitrobenzene in chloroform gave a Schiffʹs base, 4-(2-amino-5-nitrophenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-β-d-ribofuranosyl)isoxazole in 82% yield with no trace of the other regioisomer. The cyclocondensation of the resulting Schiffʹs base in benzene containing trifluoroacetic acid (TFA) gave 3-cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-β-d-ribofuranosyl)-1H-1,5-benzodiazepine in 49% yield. The same reaction of isoxazole carbaldeyde with 1,2-diamino-4-methoxy- and 4-chlorobenzenes afforded the corresponding Schiffʹs bases. Extending the reaction time for Schiffʹs base gave the corresponding cyanobenzodiazepines in good yields. Debenzoylation of the compounds with sodium methoxide produced deprotected C-nucleosides.