The synthesis of a functionalized derivative of ellipticine : 5-(hydroxymethyl)-9-methoxy11-methyl-6h-pyrido[4,3-b] carbazole n-methyl carbamate

Abstract

The synthesis of 11 was examined towards the goal of preparing sufficient quantities for biological testing. The preliminary results of its activity against some human cancer tumor cells are presented.

The acid 1 was treated with thionyl chloride and then dimethyl amine to give the amide 2 in excellent yield. The reduction of this amide with lithium aluminum hydride followed by treatment with methyl iodide gave a good yield of the methiodide 1. The displacement of trimethylamine from 1 by heating it with potassium cyanide gave the nitrile 4 in low yield. Methanolysis of 4 cleanly gave the ester 5. The acid catalyzed condensation of 5 with 3-acetylpyridine followed by quaternization at the pyridine nitrogen with 4-nitrobenzyl bromide gave the salt 7 in good yield. The intermolecular ring closure that converted 7 into 8 occurred in nearly quantitative yield. The dequaternization of 8 by heating with tributylphosphine gave the ester 9 in an acceptable yield. Reduction of 9 with lithium aluminum hydride gave an excellent yield of the alcohol 10. Treatment of 10 with 4-dimethylaminopyridine and excess methyl isocyanate gave the title compound in an acceptable yield.