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-nitrophenyl)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-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 Schiffs bases. Extending the reaction time for Schiffs base gave the corresponding cyanobenzodiazepines in good yields. Debenzoylation of the compounds with sodium methoxide produced deprotected C-nucleosides.
Nishimura
N
N
Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan.
Hisamitsu
H
H
Sugiura
M
M
Maeba
I
I
D000447:Aldehydes / Q000138:chemical synthesis*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry; D007555:Isoxazoles / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010655:Phenylenediamines; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment
C421204:5-(2,3,5-tri-O-benzoyl-ribofuranosyl)-isoxazole-4-carbaldehyde; D000447:Aldehydes; D007555:Isoxazoles; D009705:Nucleosides; D010655:Phenylenediamines; D012545:Schiff Bases; D001569:Benzodiazepines; C034193:1,2-diaminobenzene