The Importance of Alkaloidal Functions

The importance of the C-3 functionality and its attendant effect on conformation is illustrated by the discovery of the oxazolidinedione vinzoli-dine (107). This group of compounds represents a serendipitous observation of an orally active vinca alkaloid, but unfortunately the clinical application of this compound was not fully realized. 

Functionalized oxazatwistanes with phenolic OH group and nonnatural configuration at C3 (see Schemes 12.19 and 12.21) have shown their utility as organocatalysts in a growing number of reactions [15], underscoring the importance of fundamental research in cinchona alkaloids and the careful investigation of substituent effects. 

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

The importance of 3,4-dioxy function was underlined by Halton et al. who observed that the reaction did not proceed in the absence of these substituents [115]. However, the presence of this function is only a necessary, but not a sufficient condition for the success of the coupling reaction. Elegant syntheses of lignans and aporphine alkaloids are typical examples demonstrating the synthetic value of this approach [116]. 

The ecosystem consists of biological community and physical environment of the area, in which community is established and spends its Ufe. In communities and all organisms, the endo- and exometabolomics important for normal functionality depends on the ecosystem conditions. Therefore the appearance of alkaloids is dependent also on the species and biocoenose life factors. 

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