Insecticidal terpenoids

The increased resistance of some primitive and wild strains of cotton to bollworms and tobacco budworms has been attributed to certain terpenoids. Some of these were isolated from flower bud extracts and have been identified as hemigossypolone (64), heliocide H2 (65), heliocide H3 (66), heliocide H, (67) and heliocide M (68). 

The structmes of the isolated compounds have also been confirmed by synthesis (Gray et al., 1976 Stipanovic et al., 1978). 

Heiiocide H, proved to be four or five times as toxic to insects as hemigossy-polone or heiiocide Hj. This indicates that the insecticidal activity within this class is highly dependent on the stereochemistry of the products. According to Stipanovic et al. (1978), it should be possible to breed cotton varieties that contain the most effective mixture of heliocides. 

(1968a) Proc. 13th Internal. Congr. Entomol., Moscow. 

Bullivant, M. J. and Pattenden, G. (1974) lUPAC, Third Internal. Congr. Pestic. Chem.. Helsinki, Abstr. Book, 342. 

---

Fig. (27). Structures of the 30 convulsant/insecticidal terpenoids of the seco-prezizaane (1-13) and picrotoxane/picrodendrane types (14-30) whose binding data to rat and housefly GABA receptors were included in the Quasar receptor-surface modelling study [163].

A few individual terpenoids, as well as less expensive mixtures of these compounds, find practical applications. Some examples are the tli terpenoid Vitamin A, the sesquiterpenoid santonin (as an anthelmintic), and the pyrcthnns, pyrctholonc esters of the monoterpenoid chrysanthcmic acid (used as an insecticide). A number of sesquiterpenoid lactones of the germacranolide. guaianolide and elemanolide types have shown promise as rumor inhibitors. 

Several terpenoids, particularly those with a lactone moiety, have been examined for plant growth-regulating activity. Incidentally, several of these compounds exhibit anti-tumor and insecticidal activity. They are classified into mono-(CjQ), sesqui-(Ci5), di-(C2Q), tri-(Cgg) and tetraterpenes (C40) Some representative candidates among these classes possessing biological activity are as follows ... 

Among the various classes of natural products, the terpenoids have sometime occupied a special position and received chemist s attention. A large number of these compounds exhibit significant biological activities such as antifungal, antibacterial, antiviral, antitumor and insecticidal properties. The interest in this type of natural products is manifested by a large number of articles dealing with their isolation and synthesis that appear in scientific literature [1]. In recent decades an enormous effort has been focused on the development of new methods for the stereoselective synthesis of the above-mentioned diterpenes. 

More epoxides (1) with juvenile hormone activity (Vol. 2, p. 7) have been made by epoxidizing the Wittig products of citronellal (2), and some of these substances also increase silk production.Reduction of the double bond sometimes increases the activity against Oncopeltus fasciatus. Insecticidal activity is also reported for certain terpenoid cyclopropanes [e.g. (3), made from limonene and ethyl diazoacetate] and for isobornyl thiocyanoethyl ether (made from cam-phene and ethylene chlorohydrin followed by treatment with potassium thiocyanate). The insect-repelling activity shown by thujic acid amides (4) is... 

Bowers [7] found that some compounds used as insecticide synergists (e.g., piper-onyl butoxide) possess juvenoid activity, and so he synthesized analogues of the synergists, e.g., some aromatic terpenoid ether compounds, and examined their morphogenetic activity against T. molitor and milkweed bug, Oncopeltus fasciatus. He found the first synthetic compound (4, Fig. 25.2.2) with high activity [8]. 

Chrysanthemol from the leaves of Artemisia ludiviciana (Asteraceae) belongs to the cyclopropane monoterpenes Cinerins, jasmolins and pyrethrins (all including derivatives 1 and 11) are esters of /rara-chrysanthemic and pyrethric acid with terpenoid hydroxypentenones such as cinerolone, jasmolone and pyrethrolone. These are the active insecticidal constituents of pyrethrum recovered from dried flowers of several Chrysanthemum species (e.g. Chrysanthemum cinerariaefolium, Asteraceae). Some synthetic esters of chrysanthemic acid are also applied as insecticides. 

Plant sesquiterpenes and other terpenoids aie major detenninants of insect-plant interactions (2i 16V Many insecticidal and antifeedant terpenoids are epoxides including monoteipene Q2, 18. sesquiteipene QQ, 19-23). diteipene (Jl, 24) and triteipene derivatives (25-27) typified by the potent antifeedant azadirachtin (28-30). Most biolo cal effects have been determined with Lepidoptera and non-chrysomelid Coleoptera. Occasionally, the same compound, while normally inhibitory to herbivores, may for adapted insect species or at low concentrations have a stimulatory effect (13). Insects, in turn, synthesize their own defensive (21, and pheromonal (22) terpenoids. Plants may utilize insect pheromones such as the sesquiterpene alarm pheromone, rranj-B-famesene, in their own defense (34. 35). Inhibitory cyclic sesquiterpenes (Table I) and diterpenes (Table II) for insect herbivores have been identified from at least 28 genera of the terpenoid-rich Compositae. These studies were largely confined to extrafloral tissues. 

Figure 2. Stereostructures of some natural and derivatized insecticidal tetranortri-terpenoids isolated from Azadirachta indica and Melia azedarach.

Knowledge of the spectrum of insecticidal activity is limited for most of the terpenoids. The results of d-limonene trials against a wide range of insect groups indicate that this important constituent of citrus oil is toxic to some life stages of some species via some routes of exposure (4,5,6,2) Its utility as a broad-spectrum insecticide, however, does not seem feasible. Spectrum of repellent activity has been evaluated for several types of terpenes, and reproductive effects have been described for some chemicals (1,8). 

Topical Exposure. Dosing of female house fly females with five monoterpenoids yielded toxic effects when applied alone at high doses. d-Limonene was the most active of the five (Table I). Use of the synergist piperonyl butoxide enhanced the activity of d-limonene, pulegone, and linalool considerably, by 17, 21, and >14 fold, respectively. These results indicate that those three terpenoids insecticidal activity is expressed more fully when the oxidative detoxification process is inhibited. It is not surprising that flies can detoxify them rapidly, considering the relatively simple hydrocarbon structures of the monoterpenoids. 

Other synthetic terpenoid derivatives prepared as potential insecticides include further thiocyanato compounds among which is longifolyl thiocyano-acetate [668]. Relatively little attention would, however, seem to have been paid to the preparation of terpenoid organophosphorus compounds as potential insecticides or of terpenoid organotin compounds as potential fungicides. 

But, without doubt, the most exciting new possibilities for the control of insect pests, where terpenoids can be expected to play a major role, arise as a result of recent important advances in our understanding of insect physiology. These new approaches, which hold promise of eventually doing away with many, if not most, of the presently employed highly toxic insecticides capable... 

Himanen SJ, Nerg A, Nissinen A, Pinto DM, Stewart CN Jr, Poppy GM, Holopainen JK (2009) Effects of elevated carbon dioxide and ozone on volatile terpenoid emissions and multitrophic communication of transgenic insecticidal oilseed rape (Brassica mpus). New Phytol 181 174-186... 

Sesquiterpene lactones are secondary metabolites that belong to the group of C15 terpenoids. They are formed from three isoprene units. One of their methanol groups, a part of the isoprene group, was oxidized to lactones [10]. It constitutes an important group of secondary metabolites which play an important role in plant defense, as antimicrobials and insecticides. This group of secondary metabolites shows allelopathic prospective. 

Stipanovic R D, Bell A A, 0 Brien D H, Lukefahr M J 1978 Heliocide Hj. A new insecticidal C25 terpenoid from cotton. J Agr Food Chem 26 115-118... 

DDT was first synthesized in 1874 and its insecticidal properties discovered in 1939. Technical DDT is a stable, white, amorphous powder composed of up to 14 analogs and isomers. In 1942, hexachlorocyclohexane (benzene hexachloride) was discovered to be an effective and simple insecticide. Of its isomers, y-HCH has the greatest insecticidal activity and is marketed as lindane, whereas a-HCH and )3-HCH are more toxic to mammals. Chlordane, a mixture of terpenoid compounds, was discovered in 1945 to be a highly effective residual insecticide. In 1948, the most active principle of chlordane, termed heptachlor, was developed, along with two other cyclodiene derivatives, aldrin and dieldrin. It has been subsequently shown that microbial conversion of heptachlor in the environment yields heptachlor epoxide, which exhibits toxicity equal to or greater than that of the parent compound whereas photochemical conversion yields the equally toxic photoheptachlor. Also during 1948, a product obtained by the chlorination of turpentine and containing a considerable number of chlorinated camphenes was sold as toxaphene. 

Isman, M.B., H. Matsuura, S. MacKinnon, T. Durst, G.H.N. Towers J.T. Amason. 1996. Phytochemistry of the Meliaceae so many terpenoids, so few insecticides. In Phytochemical Diversity and Redundancy in Ecological Interactions, eds. J.T. Romeo, J.A. Saunders P. Barbosa, pp. 155-178, Plenum Press, New York. 

---