Synthesis and biological evaluation of new salicylate macrolactones from anacardic acids

Abstract

No âmbito de uma linha de pesquisa que visa a obtenção de novas substâncias bioativas, a partir de lipídeos fenólicos não-isoprenóides de Anacardium occidentale, descrevemos a síntese e avaliação citotóxica de novas macrolactonas salicílicas, preparadas a partir da mistura de ácidos anacárdicos, principal constituinte do líquido da casca da castanha de caju (LCC) in natura.In connection with our ongoing investigation in the search for new bioactive compounds using non-isoprenoid phenolic lipids from Anacardium occidentale as starting material, we describe the synthesis and cytotoxicity screening of some novel salicylate macrolactones prepared from anacardic acids, the major constitutents of natural cashew nut-shell liquid (CNSL). Keywords: cashew nut shell liquid, anacardic acids, salicylate macrolactones IntroductionNon-isoprenoid phenolic lipids exist in plants from a number of different families, notably the Anacardiaceae shrub, many small plants, and certain bacterial sources. The cashew tree (Anacardium occidentale), a species originally native to Brazil where it is still cultivated, also grown in a large number of other tropical and sub-tropical countries, represents one of the major and cheapest sources of this class of compounds. 1 As the main component of natural cashew nut-shell liquid (CNSL), anacardic acids (1) are the most widely distributed phenolic lipids. Chemically, the anacardic acids feature a convenient salicylic acid system and a long sidechain at the 6-position, in which a double bond is found at C-8 in the monoene, diene and triene components ( Figure 1). Anacardic acids are reported to exhibit a variety of biological activities, 2 and also have stimulated much research in order to prepare drug analogues for application in several fields. 3 In the course of ongoing investigations aiming at new drug candidates, the particular structural behavior and abundance of anacardic acids have prompted us to search for a strategy to convert these materials into analogues of an emerging family of antitumor natural products, for example: oximidines I, II, and III, 4 apicularens A and B, 5 and salicylhalamides A and B 6 (Figure 2), which present a benzofused macrolactone bearing an unusual N-acylated enamide 1218 Logrado et al. J. Braz. Chem. Soc. side-chain. Related to the fact that these benzolactone enamides do not display any significant structural correlations to the profiles of known anti-cancer drugs, they constitute a very attractive new class of lead compounds in the search for antineoplastic agents and have therefore shown considerable interest concerning to isolation, chemical synthesis and mechanistic studies of the biochemical mode of action. [4][5][6][7] Other macrolactones structurally related to the above macrolides include lasiodiplodin, 8 cis-and transresorcylide, 9 and curvularin 10 ( Figure 3). These orsellinic acid type macrolides also have attracted the attention of many synthetic chemists regarding both chemical and physiological activities. 11-13 For instance, methyldehydrola...

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Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

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