synthesis of acridine-based dna bis-intercalating agentsdna合成acridine-based bis-intercalating代理.pdfVIP

Molecules 2001, 6, 230-243 molecules ISSN 1420-3049 Synthesis of Acridine-based DNA Bis-intercalating Agents Gerard P. Moloney1*, David P. Kelly2, P. Mack2 1 The Austin Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia. Fax (03) 2 University of Melbourne, Swanston Street Parkville, Victoria 3052, Australia. *Author to whom correspondence should be addressed; e-mail: G.Moloney@.au Received: 12 July 2000; in revised form 30 August 2000 / Accepted: 18 January 2001/ Published: 28 February 2001 1 8 4 Abstract: Methods for the synthesis of N , N -bis(9-acridinyl)-N -(4-hydroxybenzyl)- 1 7 spermidine and N , N -(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-methoxy- benzylamine. 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