Synthesis of 6h-pyrido[4,3-b]carbazoles

Abstract

A few 6H-pyrido[4,3-b]carbazoles were prepared for cytotoxicity testing in cultures of human lung cancer cells. Methyl 6-methoxyindoleacetate 13 , prepared by reduction of methyl 4-(2-nitro-5-methoxyphenyl)-3-oxobutyrate 11 , was condensed with 3-acetylpyridine to give the vinyl indole 14 which was quarternized with p-nitrobenzyl bromide. Cyclization of this salt with the aid of sodium methoxide and ethyl nicotinate methiodide gave the 6H-pyrido[4,3-b]carbazole 16 . Brief treatment with tributyl phosphine in boiling DMF gave the ester 17 which, after reduction with LilH4 followed by treatment with methyl isocyanate, gave 5-hydroxymethyl-9-methoxy-11-methyl-6H-pyrido[4,3-b] carbazole N-methylcarbamate 4 9-Methoxyolivacine 19 was oxidized to the aldehyde 22 with seO 2. Reduction to the carbinol 24 . proceeded smoothly with NaCNBH 3 in acid medium. Treatment with methyl isocyanate gave the carbamate 6 and the acetate 7 was prepared by acetylation of the carbinol 24 .