Tetrahedron, Vol. 53. No. 5, 1743-1750, pp. 1997 Copyright Q 1997 Elsevier Science Ltd Printed in Great Britain. All rights reserved PII: SOO40-4020(96)01096-4 0040-4020/97 $17.00 + 0.00 Total Synthesis of the Marine Pentacyclic Alkaloid Meridine Nataly Bontemps, Evelyne Delfourne *, Jean Bastide, Christian Francisco and Franz Brachers Unkrsitb de Perpignw Centre de Phyropharrnacie URA CNRS 461,52 avenue de Villeneuve, 66860 Perpgnan Cedex, France, 9 lnstihlt ftir Pharmazeutlsche Chemie, Bmthovenstr. 55, 38106 Braunschweig, Germany Abstract : The synthesis of the marine pyridoacndine alkaloid merldrne (1) has been accomplished in eght steps from 25 dimethoxy-3-nitroanlllne m 9 % overall yield. 0 1997, Elsevier Science Ltd. All rights reserved. Marine organisms constitute a source of natural products in which unique biologically active structures account for the continuing interest in these compounds. 1 Meridine 1, a marine alkaloid was isolated by Schmitz et al. from the ascidian Amphicarpa meridiana. 2 For our part, we recently reported on the isolation and structure elucidation of cystodamine 2, another structurally related novel pentacyclic alkaloid from the Mediterranean ascidian Cysrodyres dellechiajei.3 Because of the general cytotoxicity of this family, and the few biological studies on meridine,4 we were interested in devising a synthesis of this compound that would generate intermediates that might possess potential anti-tumor properties. The recently reported synthesis of 1 by Kitahara et al.5 based on an hetero-Diels-Alder strategy prompts us to report our quite different approach. 2 l,R=OH 2, R = NH2 Fax : 33 04 68 66 22 23. E. mail : delfourne@univ-perpfr 1743