Novel ring transformation of 5-(2,3,5-tri-O-benzoyl-beta-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-(beta -D-ribofuranosyl)-1H-1,5- benzodiazepines were reported. Treatment of isoxazole carbaldehyde with 1,2 -diamino-4-nitrobenzene in chloroform gave a Schiffs base, 4-(2-amino-5-nit rophenyl)iminomethyl-5-(2,3,5-tri-O-benzoyl-beta -D-ribofuranosyl)isoxazole in 82% yield with no trace of the other regioisomer. The cyclocondensation of the resulting Schiffs base in benzene containing trifluoroacetic acid ( TFA) gave 3-cyano-8-nitro-4-(2,3,5-tri-O-benzoyl-beta -D-rbofuranosyl)-1H-1 ,5-benzodiazepine in 49% yield. The same reac tion of isoxazole carbaldeyde with 1,2-diamino-4-methoxy- and 4-chlorobenzenes afforded the correspondin g Schiffs bases. Extending the reaction time for Schiff's base gave the cor responding cyanobenzodiazepines in good yields. Debenzoylation of the compo unds with sodium methoxide produced deprotected C-nucleosides. (C) 2000 Els evier Science Ltd. All rights reserved.