Limonoid structures

Acetylnimbandiol was insectidical (EI50 = 21 ppm) when fed to the larvae of II. vlrescens, while the structurally related salannin, which lacks the A-ring ketone (Figure 13), was not (Table VII) (57). Nakanishi (58) has pointed out that natural products with electrophilic moieties tend to be cytotoxic and insect antifeedant. Possibly the growth-Inhibitory activity of the limonoids may also be attributed to a nonspecific electrophilic effect. 

Figure 13o Structures of Some Insect Growth Inhibitory Limonoids Isolated from Plant Species in the Meliaceae...

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. 

Anthothecol (94) and hirtin (95) have been interrelated via the trione (96). Dysobinin (97) is a new tetranortriterpenoid from Dysoxylum binectariferum7 An intermediate in a projected limonoid synthesis has been shown to have structure (98) by X-ray analysis. ... 

Other studies show the presence of a diversity of compounds other than limonoids as defenses in the tissues of Meliaceae. Woody tissues of Trichilia trifolia afforded three novel dolabellanes with flexible Curing structures. These substances were very active antifeedants in the Sitophilus bioassay (Ramirez et al., 2000). T. martiana seeds yielded large amounts of 2-((Z,Z)-6,9-heptadecadienyl)furan. T. hirta and T. americana bark have yielded novel steroids by insect bioassay-guided isolation and application of a nanoprobe nuclear magnetic resonance (NMR) technique for structure elucidation (Chaurest etal.,1996). Compounds isolated included hydroxyandrosta-l,4-diene-3,16-dione (Fig. 1.4) and derivatives. However, studies by Wheeler et al. (2001) suggest that other unidentified compounds may also be... 

Pseudomonas sp. 321-18 (21). Hydrolyzing activity is optimal at pH 8.0, whereas lactonizing activity is optimal at pH 6.0. The enzyme attacks limonoids whose structures differ from I in the vicinity of the A or A -ring. The enzyme does not attack XVI and XVIII. 

The powerful antifeedant and insecticide azadirachtin (213), from the neem tree (Azadirachta indica, Meliaceae), is a highly oxidized limonoid with rings A, B, and D intact.2 It is used as a benchmark against which all other antifeedants can be compared (vide infra). The total synthesis of azadirachtin has recently been achieved in 64 steps.96 This is very unlikely to provide a synthetic source of the compound, but it does allow SAR studies to find maximum activity, and opens up the field to possible simpler synthetics modelled on it. As yet, even slight modifications of the structure tend to decrease activity. Azadirachtin (213) has been available commercially, particularly in the United States, but at present the cost of the seeds and the isolation procedure inhibit its wider use. 

Figure 7.6 Structures of the withanolides (14), cardiac glycosides (15) and limonoids (16).

Full papers have appeared on the conversion of turreanthin and its congeners into simple limonoids, the rearrangement of melianone into apotirucallol derivatives," and the structures of azadirone, azadiradione, and epoxyazadira-dione from Melia azadirachta ... 

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... 

BicydononanoUdes.—Utilin, C41H52O17, a complex limonoid from Entandro-phragma utile, has been shown by X-my analysis to have the structure (93) with the unprecedented feature of bond formation between one of the C-4 methyl... 

Quassinoids.—Simarolide (136) had previously been the only substance providing a structural link between limonoids and quassinoids. The related picrasin A (137) has now been isolated from Picrasma quassioides P. ailan-thoides). It was accompanied in the extract by picrasin B (138) which was converted to quassin (139) by bismuth oxide oxidation and methylation. A series of closely related quassin derivatives, nigakilactones A (140), B (141), C (142), E (143), and F (144) occur with quassin in P. ailanthoides. - The structure of amarolide has been revised to (145). Observation of a large coupling between H-9 and H-11 in the n.m.r. spectrum makes the previous... 

The structure of phragmalin (75), a complex limonoid from Entandrophragma caiidatum, has been determined by X-ray analysis." It is closely related to utilin (see Vol. I, p. 177) and occurs in combination with nicotinic and isobutyric acids. 

Tetranortriterpenoids.— Two further new limonoids from Melia azedarach are ohchinolides A (44) and B (45). X-Ray analysis confirmed the structure of ohchinolide Other new limonoids reported this year are pseudrelone B (46) from Pseudocedrela kotschyii (Meliaceae), febrinins A (47) and B (48)... 

In this chapter, our recent studies on the Insecticidal constituents from these two plant species will be presented, concentrating first on the volatile organosulfur compounds recently Isolated from neem seeds (, and then on the azadirachtin-type tetranortrlterpenoid limonoids present In both species (22-26). Our recent studies on the Insecticidal mellaclns of the azadirachtin type suggest structure-activity relationships and a mode of action which may be useful In the design of synthetic analogs. 

To use a more sophisticated example, we can look to the products of the neem tree (Azadirzchta indica), a tropical plant that is known for its pesticidal properties. The seed of this tree is abundant with limonoids and simple terpenoids that are responsible for its biological activity. One particular limonoid found in the seed is Azadirachtin (2.134). The bioactivity of Azadirachtin potentially leads to a wide range of applications in herbal medicine and healthcare products for the treatment of malaria and tuberculosis and in anti-worm, clotting, and blood-detoxification preparations. These uses of Azadirachtin as a biopesticide or herbal medicine is limited due to solubility constraints in water and its instability as a result of its propensity to undergo complicated, irreversible rearrangements under acidic, basic and photolytic conditions. Consequently, there has been much research in the structural modification of Azadirachtin to overcome its solubility constraints to increase stability. This process normally involves many protection and deprotection synthetic steps and chromatographic separations. 

Broughton H B, Ley S V, Slawin A M Z, Williams D J, Morgan E D 1986 X-Ray crystallographic structure determination of detigloyldihydroazadirachtin and reassignment of the structure of the limonoid insect antifeedant azadirachtin. J Chem Soc Chem Commun 46-47... 

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