Terpenoids limonoids

Radioactive tracer work has shown that nomilin (3) is biosynthesized by the terpenoid pathway from acetate in the phloem region of stems and translocated to other parts of plants such as leaves, fruit tissues and seeds (13,14). At those locations, nomilin is further biosynthesized to other limonoids. Limonoid biosynthesis occurs at each location independently, thus the composition of limonoids in fruit tissues, seeds and leaves are different from each of the others. Limonin is biosynthesized from nomilin via obacunone (4), obacunoate (5) and ichangin (6) (15-17) (Fig. 2)... 

Bitter terpenoids, known as limonoids, are biosynthetically related to the quassinoids that are produced by species of Meliaceae. One well known representative from this family is Azadirachata indica, the neem tree, widely used as an antiplasmodial plant in Asia. Rochanakij... 

Calodendrolide (76), a novel degraded terpenoid, has been isolated from Calodendron capense (Rutaceae). It was readily converted into pyroangolen-solide (77) by hydriodic acid. Calodendrolide co-occurs with other limonoids... 

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. 

Nomilin the general biosynthetic precursor of all limonoids, is biosynthesized via the terpenoid pathway from acetate and/or mevalonate in stems. Nomilin is then translocated to other plant tissues, including leaves, seeds, and fruit tissues, where it is converted to the other limonoids independently (Hasegawa et al. 1986 Ou et al. 1988). In most citrus species and hybrids, nomilin is converted to obacunone and then to obacunoate. Obacunaote is then converted to limonin probably via the intermediate ichangin. Nomilinic acid is the predominant acidic limonoid in citrus, but it does not seem to be directly involved in the biosynthetic pathways of major limonoids. 

Figure 7.29 Citrus fruit are a rich source of terpenoids including the Cio diterpenes (+)- and (—)-limonene and a number of more complex limonoids which are distinctive in that the glucosides are tasteless while the aglycones have a bitter taste.

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