Quassinoid families

The alkylating-cyclization method may be extended to the enantioselective introduction of an alkyl chain, if a chiral alcohol is used as starting material. The tributyltin hydride mediated radical cyclization of the bromoacetal of 18,19-bisnor-9/i-podocarp-l 3-en-12-one gives a tetracyclic d-lactone, the characteristic structural feature of quassinoids, a complex family of degraded triterpenes82. The hydrogen abstraction in the last step of the reaction has to occur stereoselectively, because only two C-16 diastereomers are formed during the reaction. 

Crude extracts of the root bark from Celastrus paniculatus Willd. (Celastraceae) demonstrated significant activity against cultured P. falciparum (93), and the active principle was shown to be pristimerin, a quinonoid triterpene. The family Simaroubaceae has also yielded a number of compounds with in vivo and in vitro antimalarial activity (94-96) including quassinoids. Bruceantin has been most extensively studied, but is very cytotoxic however, other quassinoids are relatively less toxic to cultured KB cells while retaining potent antimalarial activity (88). Plants from the Meliaceae are commonly used as febrifuges in Africa, and several limonoids from this family, such as nimbolide and gedunin, have also been found to produce moderate inhibition of cultured P. falciparum (97,98). 

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... 

Two major groups of metabolically altered tiiterpenes, the limonoids (tetranortriterpenoids) and the quassinoids (decanortriterpenoids) are derived from euphol (1) (Fig. 25.1) or tirucallol (2) (Fig. 25.2). To date, these compounds are restricted in distribution to the Rutaceae, Meliaceae, Cneora-ceae, Simaroubaceae, and, perhaps, the Burseraceae (Connolly and Hill, 1991), and occur variously in seeds, fruits, and wood of plants of these families. In general, the limonoid and quassinoid content of leaves has not been examined (Taylor, 1983). 

Quassinoids are decanortriterpenes known to occur only in the family Simaroubaceae (Polonsky, 1983, 1986). More than 120 compounds and 5 major structural types have been described (Polonsky, 1986). 

A literature search conducted for the terms quassinoid and simaroubolide (a term used in the 1970s to designate these molecules isolated from plants of the Simaroubaceae family) on the search engines Scopus and Science Direct provided a total of 453 references from 1970 to 2011 Fig. 125.7 illustrates the yearly profile. 

This graph highlights the growing interest in quassinoids between the 1970s and 1980s. This trend could be explained simply by the increasing number of scientific publications at the time, but a study of the literature shows clearly that it is also correlated with the discovery of the anticancer properties of these molecules. Since 1990, the number of articles on this family of molecules has remained stable. 

More than ten years have elapsed since the publication of a comprehensive review on the quassinoids, the bitter principles of the Simaroubaceae family (80). Interest in these terpenoids has increased enormously in recent years due in part to the finding of the American National Cancer Institute in the early 1970s that these compounds display marked antileukemic activity. Furthermore, a wide spectrum of other biological properties for the quassinoids has been discovered and studies on chemical modifications of inactive members to yield biologically active ones were undertaken. New structures have been established also and numerous synthetic approaches have been developed which include the total synthesis of the parent compound, quassin (p. 250) and also that of castelanolide (p. 253). 

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