900 Research Article Received: 24 October 2008 Revised: 19 December 2008 Accepted: 27 January 2009 Published online in Wiley Interscience: 5 May 2009 (www.interscience.wiley.com) DOI 10.1002/ps.1771 Synthesis and insecticidal activity of new pyrethroids Flaviano O Silv ´ erio, a Elson S de Alvarenga, a* Shaiene C Moreno b and Marcelo C Picanc ¸o b Abstract BACKGROUND: Pyrethroids are among the most potent pesticides known, with great potential for structural variation with retention or enhancement of potency. The simple methyl ester is easier to prepare (at least one step shorter) than the more complex pyrethroids modified on the alcohol moiety. The objective was to synthesise methyl esters of pyrethroid acids containing an aromatic ring on the acid moiety and evaluate their biological activity against Ascia monuste orseis Latr., Tuta absoluta Meyrick, Periplaneta americana (L.), Musca domestica L. and Sitophilus zeamais (Motsch.). RESULTS: The synthetic sequence required seven steps: protection of the hydroxyl groups of D-mannitol, diol oxidative cleavage with sodium metaperiodate, alkene formation by Wittig reaction with methoxycarbonylmethylidene(triphenyl)phosphorane, cyclopropanation, acetal hydrolysis with perchloric acid and oxidative cleavage with sodium metaperiodate gave methyl (1S, 3S)-3-formyl-2,2-dimethylcyclopropane-1-carboxylate. The final step comprised reaction of the aldehyde with five different aromatic phosphorus ylides to give the pyrethroids. CONCLUSION: An efficient and versatile synthesis of ten new pyrethroid methyl esters has been accomplished from the readily available D-mannitol in seven steps. All compounds showed insecticidal activity, and methyl (1S,3S)-3-[(Z)-2-(4- chlorophenyl)vinyl]-2,2-dimethylcyclopropane-1-carboxylate was the most active, killing 90% of A. monuste orseis and 100% of T. absoluta and P. americana. c  2009 Society of Chemical Industry Keywords: insecticide activity; pyrethroids; pyrethrins; Periplaneta americana; Ascia monuste orseis; Tuta absoluta 1 INTRODUCTION Pyrethroids are among the most potent pesticides known, with great potential for structural variation with retention or enhancement of potency. Their importance arises from their outstanding rapid knockdown action on flying insects, combined with a very low mammalian toxicity. 1–5 The presence of aromatic groups on the alcoholic moiety increases the stability of the pyrethroids in the presence of air and light in relation to the natural pyrethrins (Fig. 1). This increased stability made possible the use of the pyrethroids in crop protection, thus leading to considerable structural modifications on this part of the molecule. 6–8 While a large variety of modifications have been performed on both the alcohol and acid portions, there are no reports of insecticidal activity for the simple methyl esters with an aromatic ring on the acid moiety. 8,9 A great number of methyl esters are known in the literature as intermediates, but their insecticidal activity has not been evaluated. The methyl esters could be transformed into other pyrethroids by modifying the alcohol moiety, but that would require at best a further step (transesterification). The simple methyl ester is more viable economically (cheaper to prepare) than the more complex pyrethroids modified on the alcohol moiety. The methyl esters are stable, as are the commercial pyrethroids, to air and light, and could be employed in crop protection. Some of the aryl groups in the acid portion were selected from the more complex m-phenoxybenzyl esters, which are known insecticides. 10 The insecticidal activity of the synthesised compounds against five insect species of economic importance, Ascia monuste orseis Latr. (Lepidoptera: Pyralidae), Tuta absoluta Meyrick (Lepidoptera: Gelechiidae), Periplaneta americana (L.) (Dictyoptera: Blattidae), Musca domestica L. (Diptera: Muscidae) and Sitophilus zeamais Motsch. (Coleoptera: Curculionidae), were evaluated. These species represent four different orders of insects. The kale leaf worm, A. monuste orseis, is a key pest of Brassicaceae (kale, cabbage, cauliflower, broccoli, mustard and radish), mainly in subtropical and tropical regions. 11 The tomato leafminer, T. absoluta, is one of the main pests of tomato crop nowadays. Its larvae attack leaves, stems, sprouts, flowers and fruits, causing severe damage to the crop. 12 Sitophilus zeamais, the maize weevil, is a cosmopolitan grain-store pest, mainly in maize, and in the south of Brazil has been causing great damage in several fruitful cultures, such as ∗ Correspondence to: Elson S de Alvarenga, Departamento de Qu´ ımica, Univer- sidade Federal de Vic ¸osa, 36570-000 Vic ¸osa, Brazil. E-mail: elson@ufv.br a Departamento de Qu´ ımica, Universidade Federal de Vic ¸osa, 36570-000 Vic ¸osa, Brazil b Departamento de Biologia Animal, Universidade Federal de Vic ¸osa, 36570-000 Vic ¸osa, Brazil Pest Manag Sci 2009; 65: 900–905 www.soci.org c  2009 Society of Chemical Industry