Dimethyl 6-Amino-1-methyl-9H-carbazole-2,3-dicarboxylate

Abstract

Abstract:The title compound (2) was prepared in high yield by catalytic transfer hydrogenation of the 6-nitro precursor (1), using hydrazine hydrate as the hydrogen source. Under the conditions employed, the ester groups remain unaffected. The new compound was fully characterised by elemental analysis, . Such compounds are known to act as topoisomerase II poisons and as another common structural feature they possess a heteroaromatic ring fused to the carbazole 2,3-bond. Typically, this is a pyridine unit (like in olivacine and its isomer, ellipticine [3]), but there are also examples for various diazine-fused 1-methyl-and 1,4-dimethylcarbazoles, exhibiting antitumor activity [4]. Among them, pyridazino [4,5-b]carbazoles (representing a 3-aza-olivacine scaffold) have been reported by us [5][6][7][8] and others [9]. As a key intermediate for the synthesis of these tetracycles, 1-methylcarbazole-2,3-dicarboxylic esters have been used and the latter were found to provide a convenient access also to some cytotoxic 4-methylpyrrolo [3,4-b]carbazole-1,3(2H,5H)-diones [10], which again feature the 1-methylcarbazole motif. In the course of extensive structural variation of the A-ring substitution pattern of such b-fused 1-methylcarbazoles, we recently reported the synthesis and cyclisation reactions of some halo-and nitro-substituted 1-methylcarbazole-2,3-dicarboxylic acid dimethyl esters [11]. As a further extension of our building-block library, we here describe the convenient preparation of dimethyl 6-amino-1-OPEN ACCESS

Position-Selective Synthesis and Biological Evaluation of Four Isomeric A-Ring Amino Derivatives of the Alkaloid Luotonin A

“…With the 2-nitro compound 4a [ 16 ] and the new 4-nitro isomer 4b in hands, preparation of the corresponding two amino-substituted Luotonin A derivatives should be feasible in a straightforward manner by reduction of the NO 2 group. While Cagir et al [ 20 ] had obtained 8-amino-Luotonin A from the 8-nitro precursor by reduction with SnCl 2 in moderate yield (40%) and Dallavalle et al [ 25 ] had reported an unsuccessful attempt to selectively reduce the nitro group in 9-nitro-Luotinin A by catalytic hydrogenation in acetic acid, we decided to apply a protocol that had been successfully used for the reduction of nitrocarbazoles into aminocarbazoles [ 26 , 27 ]. This method makes use of hydrazine hydrate as hydrogen source in a catalytic transfer hydrogenation reaction in alcoholic solution or suspension at elevated temperature.…”

9-Aminoquino[2',3':3,4]pyrrolo[2,1-b]quinazolin-11(13H)-one

“…Replacement of gaseous hydrogen with liquid or solid hydrogen sources in catalytic hydrogenation reactions is generally referred to as catalytic transfer hydrogenation [13] and it offers some advantages in terms of safety, as well as easier reaction monitoring and (in some cases) easier work-up. We previously made positive experiences with the selective reduction of a nitrocarbazolediester by catalytic transfer hydrogenation [14], employing Deady's protocol [15]. Recently, we successfully employed this technique also to the synthesis of A-ring amino derivatives of Luotonin A [4].…”