Macrolide insecticide

Various examples of use of alkenyltin/vinyl iodide couplings in natural-product synthesis have been provided Evans and Black [33] have obtained the macrolide insecticide (+)-A83 453A [(+)-lepicidin A] (Scheme 4-7), Burke et al. the ionophore antibiotic X-14547A [34] (Scheme 4-8), Kende et al. [35] lankacidin C (Scheme 4-9), while Han and Wiemer [36] have used the combination alkenyltin/vinyl triflate in the total synthesis of (+)-jatrophone. 

Research to date focused on isolating insecticidal prototype leads from marine origin has resulted in the report of about 40 active compounds.44 In an attempt to summarize these compounds and their activity margins, they have been categorized into seven classes of chemical structures polyhalogenated monoterpenes, polyhalogenated C15-metabolites, diterpenes, peptides and amino acids, phosphate esters, sulfur-containing derivatives, and macrolides. 

The antifungal macrolide halichondramide (3), isolated from the Kwajalein sponge of the genus Halichondria, showed significant insecticidal activity at 3 ppm, especially against tobacco budworm. We isolated swinholides A (4) and B (5), from the Red Sea sponge The-onella swinhoei. 

We mentioned earlier the in vitro antimalarial activity of halichondramide and swin-holide A.22 The initial testing of compounds 3 to 5 displayed 75 to 100% mortality of both corn rootworm and tobacco budworm. On titration, they displayed an LCS0 range of 10 to 100 ppm, and induced 30, 85, and 30% corn rootworm larval stunting, respectively. Both halichondramide and swinholide A caused 85% tobacco budworm larval stunting. The significant insecticidal activity of these compounds (3 to 5) indicates that further QSAR studies of the compounds would be valuable. These compounds illustrate the necessity to examine various marine macrolides as potential prototype insecticides. 

The avermectins (Figure 3.67) have no antibacterial activity, but possess anthelmintic, insecticidal, and acaricidal properties, and these are exploited in human and veterinary medicine. The avermectins are also 16-membered macrolides, but their structures are made up from a much longer... 

Macrolide compounds with a hygrolide skeleton such as L-681,110 Bx (14 in Figure 3),44 leucanicidin (15),45 and bafilomycin Ai (16)46 produced by Streptomyces species were shown to have insecticidal activity by inhibiting H+-ATPase.47 They are useful as biological reagents. 

S-Hydroxylation of milbemycins 54a-c, 16-membered ring macrolides isolated from Streptomyces hygroscopicus and showing potent and broad spectrum activity as anthelmintics, acaricides and insecticides, was found to be relatively efficient (yields around 50%) by selenium dioxide oxidation in formic acid and subsequent acidic hydrolysis (Scheme 6) [21]. 

It has been shown for avermectin B that the hydroxyl group at C-5 and a disaccharide moiety are essential for antiparasitic, mitocidal and selective insecticidal activities. Chemical modification of the macrolide-type avermectins resulted in ivermectin which was commercialized to be used in agriculture and animal health care as well as in human medicine. 

These are a family of novel macrolide antibiotics with high order of insecticidal and ascaricidal properties. The miibemycins are structurally related to the aver-mectins except for the fact that they have no substitution at position 13 and, therefore, may be called 13-deoxyavermectin aglycones. Originally nine miibemycins were isolated from the broth of Streptomyces hygroscopicus, subsp. aureolacrimosus [24,25]. Various other milbemycin derivatives were produced by fermentation of different strains of Streptomyces such as strain MA-5920 (prepared by fusion of S. aver-mitilis protoplast with S. hygroscopicus protoplast) [26], E-225 [27] and S. eurythermus [28]. The structure of the miibemycins is represented by the general formula 14 the important members of this class are milbemycin-D (15) and nemadectin (16) [29,30]. 

The avermectins (AVM) are a family of naturally occurring macrolides which are produced by Streptomyces avermitilis and possess potent broad-spectrum anthelmintic, acaricidal and insecticidal activity (25-27). One of the major components of the avermectin complex is AVM Bla. This has been shown to interfere with neurotransmission at excitatory neuronal (nerve-nerve) synapses in the ventral nerve cord of A. suum where the mode of action seems to involve a GABA-ergic mechanism (1, 3) AVM Bla also abolishes the hyper polarizing potentials recorded from muscle bags of A. suum in response to stimulation of inhibitory motorneurones O, 3.). Kass and co-workers (2, 28) suggest that the effect on inhibitory neuromuscular transmission results from blockade of GABA receptors present on the postsynaptic muscle membrane. As the postsynaptic receptors are... 

Structually much more complex molecules have also been submitted to re-gioselective enzymatic hydroxylation. Two such examples have been described involving milbemycin, a sixteen-membered macrolide which exhibits broad-spectrum insecticidal and acaricidal activity, and monensin, a carboxylic polyether antibiotic193- 94l Milbemycin (Fig. 16.1-19) was thus regioselectively hydroxylated at the 13(3 position (followed eventually by a C-29 hydroxylation) to afford the 13P,29-... 

Many macrolides have interesting biological activities such as antiviral, antibacterial, antifungal, anthelmintic, phytotoxic, insecticidal, antitumor, and immunosuppressive activities. Those activities are due to their various biochemical activities and thus some macrolides are important tools as biochemical reagents. 

This chapter deals with recent progress in the chemical modification and structure-activity relationships of 14- and 15-membered macrolides (mainly erythromycin derivatives), 16-membered macrolides (mainly the leucomycin and tylosin families), and the avermectin family of macrolides, showing nematocidal, insecticidal, and arachnidicidal activities. Previous reviews of these macrolides were given by Sakakibara and Omura in the first edition of this book in 1984 [1]. 

Agrochemicals, s also Chemicals Phytochernicab from marine environment, insecticidaL uses of amino acids, 244-245 d/tetpwtes, 243 macrolides, 245-246 overview, 242 peptides, 244-245 phosphate esters, 245... 

T. C. Barden, G. Asato, Z. H. Ahmed, D. J. France, V. Kamesvaran, E. Parker-Jackson, S. Y. Tamura, S.-S. Tseng, B. L. Boolcwalter, New Series of Milbemycin Macrolides (LL-F28249) with Endectocidal, Insecticidal, and Acaricidal Activity, ACS Symposium Series No 504, American Chemical Society, Washington DC, pp. 227-237,1992. 

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