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Synthesis of Acridine-based DNA Bis-intercalating Agents
The Austin Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia
University of Melbourne, Swanston Street Parkville, Victoria 3052, Australia
* Author to whom correspondence should be addressed.
Received: 12 July 2000; in revised form: 30 August 2001 / Accepted: 18 January 2001 / Published: 28 February 2001
Abstract: Methods for the synthesis of N1, N8-bis(9-acridinyl)-N4-(4-hydroxybenzyl)-spermidine and N1, N7-(hydroxybenzyl)-bis-(3-aminopropyl)amine were investigated. Thus monocyanoethylation of 4-methoxybenzylamine followed by treatment with 4-chlorobutyronitrile gave the dinitrile N-(2-cyanoethyl)-N-(3-cyanopropyl)-4-methoxybenzylamine. Subsequent in situ reduction with lithium aluminium hydride gave the corresponding diamine. Biscyanoethylation of 4-methoxybenzylamine with 2 mole of acrylonitrile followed by reduction yielded the diamine N, N-bis-(3-aminopropyl)-4-methoxybenzylamine. Both diamines reacted smoothly with 9-methoxyacridine to give the bis-(9-acridinyl) compounds 11 and 15 but with 4,5-dimethyl-9-methoxyacridine, the bis compound 16 was produced in only low yields. Demethylation of the dinitriles by a variety of approaches all failed to give the corresponding hydroxybenzyl derivatives. These studies yielded useful methylated tyrosine derivatives which could also be iodinated. This study has been useful for elucidating chemical methods needed for the synthesis of the desired tyrosine-based bis acridine compound and for alerting us to the need to synthesise a more labile protected tyrosine intermediate which will be easily deprotected to afford the desired tyrosine-based bis acridine compound.
Keywords: Acridine; intercalate; anti-cancer; synthesis
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MDPI and ACS Style
Moloney, G.P.; Kelly, D.P.; Mack, P. Synthesis of Acridine-based DNA Bis-intercalating Agents. Molecules 2001, 6, 230-243.
Moloney GP, Kelly DP, Mack P. Synthesis of Acridine-based DNA Bis-intercalating Agents. Molecules. 2001; 6(3):230-243.
Moloney, Gerard P.; Kelly, David P.; Mack, P. 2001. "Synthesis of Acridine-based DNA Bis-intercalating Agents." Molecules 6, no. 3: 230-243.