Azadirachtins

Azadirachtin, which is a tetranortriterpenoid, is an active ingredient of neem Azadirachta indica) seed oil. The structure of azadirachtin is as follows. It controls 200 species of insects, including locusts, gypsy moths, cockroaches, and fall army worms. It has an oral LD50in rats of 5000 mg/kg, making it essentially nontoxic to mammals. 

The neem tree, Azadirachta indica, is native to tropical Asia but has been planted widely in the warmer parts of Africa, Central and South America, and Asia. Extracts from neem seed kernels act as repellents, antifeedants, and growth disruptants. The main active principle in kernels is azadirachtin (AZ), a limonoid with a very complicated structure. A range of other compounds is also present. These neem substances can repel insects, prevent 

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An intramolecular cycloaddition reaction of 117 is the crucial step in the synthesis of the highly functionalized decalin [115] moiety of azadirachtin 119. 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

An unusual cationic domino transformation has been observed by Nicolaou and coworkers during their studies on the total synthesis of the natural product azadirachtin (1-105) [30]. Thus, exposure of the substrate 1-106 to sulfuric acid in CHjClj at 0°C led to the smooth production of diketone 1-109 in 80% yield (Scheme 1.27). The reaction is initiated by proto nation of the olefinic bond in 1-106, affording the tertiary carbocation 1-107, which undergoes a 1,5-hydride shift with concomitant disconnection of the oxygen bridge between the two domains of the molecule. Subsequent hydrolysis of the formed oxenium ion 1-108 yielded the diketone 1-109. 

Scheme 1.27. Cationic domino transformation towards the synthesis of azadirachtin (1-105).

Azadirachtin (Neem) Aza-direct, Neemix Whitefly, caterpillars, leafminer, aphid, DBmoth Various fruits and vegetables Insecticide... 

Axle and collar molecular structure, 27 60-61 Axokine, 3 97 Azaboranes, 4 170, 204 Azacarbocyanine dyes, 9 257 Aza[18]crown-6, 24 41 Aza[18]crown-6 appended a-helical barrels / rods, 24 58 Azacrown ethers, 24 44 Azacrowns, 24 41 Azacryptands, 24 42 Azadirachtin, 24 474 Azafullerenes, 22 231, 232, 243 Azahomofullerenes, 22 243 Azaindene compounds, 29 197 Azalactone method (for Emphaze supports), for covalent ligand immobilization, 6 396t Azamethiphos (salmosan)... 

Azadirachtin [11141-17-6] Bufo quercicus (stuge 12) LC50 (96-h) 0.64 Punzo, 1997... 

Punzo, F. The effects of azadirachtin on larval stages of the oak toad, Bufo quercicus (Holbrook), Florida Scientist, 60(3) 158-165, 1997. 

The seeds from the Indian neem tree, Azadirachta indica, are the source of two types of neem-derived botanical insecticides neem oil and medium polarity extracts. Neem seeds contain numerous azadirachtin (Fig. 9) analogs, but the major form is azadirachtin and the remaining minor analogs are likely to contribute little to the overall efficacy of the extracts. Typically, solvent partitions or other chemical processes are required to concentrate this active ingredient to the level of 10% to 50% seen in the technical grade material used to produce commercial products. 

The reactivity of 464 was also used to prepare perhydrofuropyrans with the same methodology as shown in Scheme 129, but with an epoxide as second electrophile. Diols 467 were obtained in 35-68% yield which, after hydroboration and oxidation reactions (as shown in Scheme 128), gave perhydrofuropyrans 468 in 57-64% yield. This heterocyclic unit is present in many natural products, azadirachtins being probably the most important ones. ... 

However, the acctimulated Information on azadirachtin, while promising, is presently much less than that needed for insecticidal product commercialization (41). The mode of action, structure-activity relationships (SAR s), formulation, and metabolism of azadirachtin are not yet well understood. Furthermore, formulation studies are required prior to product development and commercialization. Consequently, further investigations are needed before the full potential of azadirachtin as an insect control agent or insecticide can be realized. 

Azadirachtin has several effects on a number of economically important species of insect pests, including feeding deterrency. 

The growth-inhibitory activity of azadirachtin fed in artificial diet to three species of agricultural pests, gossypiella, H. zea, and frugiperda, was compared to the activity of a number of limonoids isolated from plants in the Meliaceae and the Rutaceae (Table VI). After azadirachtin, the most active limonoid was cedrelone (Figure 13). Cedrelone was unique among the compounds tested in Table VI since it was the only limonoid, besides azadirachtin, to cause an inhibition in ecdysis (LC50 = 150 ppm) when fed to pink bollworm larvae (54). 

Figure 12. Upper Previously Accepted Stereostructure of Azadirachtin (43). Lower Recently Proposed Stereostructure of Azadirachtin (37)...

Table V, Cotton Leaf Disk "Choice" Bioassay of Azadirachtin with...

PC95 values are concentrationsnf azadirachtin resulting in 95% "protection" of treated disks when compared to untreated disks. 

Another limonoid isolated from neem seeds and determined to be as potent as azadirachtin as an ecdysis inhibitor has been identified as 3-deacetylazadirachtinol (Figure 15) (57). Both compounds were lethal to 50% of the treated H. virescens larvae (EI5Q) at 0.8 ppm in artificial diet (Table VII). Structurally, there are two differences between the compounds. In 3-deacetylazadirachtinol, the C-ll-O-C-13 ether linkage of azadirachtin is reductively cleaved at the 11 position and the acetoxyl group at C-3 is hydrolyzed to a hydroxyl group. 

Table VIII. Ecdysls-Inhlbltory Activity of Azadirachtin Fed in an...

T riterp. azadirachtin-like tetranortritero. azadirachtin (neem teee,Azadirachta indicaA. Juss., Meliaceae, Ang. MI) Quassinoids (biosynthetically related to triterp.) including seco- and further degraded forms Quassia amara L., Sapindales, Ang. from Jamaica quassin DSII, and other metabolites Connolly 1997). 

Aglaja elliptica and Aglaja harmsiana, Meliaceae, Ang., of potency rivaling azadirachtin... 

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