Diterpenoids physiological activity

Over the last seventy years over sixty species of Aristolochia have been exploited for chemical examination by research groups throughout the world and a variety of compounds have been isolated. The spectrum of physiologically-active metabolites from Aristolochia species covers 14 major groups based on structure aristolochic acid derivatives, aporphines, amides, benzylisoquinolines, isoquinolones, chlorophylls, terpenoids, lignans, biphenyl ethers, flavonoids, tetralones, benzenoids, steroids, and miscellaneous. The aristolochic acid derivatives, host of phenanthrene derived metabolites were further classified into aristolochic acids, sodium salts of aristolochic acids, aristolochic acid alkyl esters, sesqui- and diterpenoid esters of aristolochic acids, aristolactams, denitroaristolochic acids, and aristolactones. The terpenoids can further be subdivided into 4 groups mono-, sesqui-, di- and tetraterpenoids. 

The physiological activity of extracts from yew species has been known for millennia. In 1856, Lucas (358) isolated a mixture of alkaloids, which he called taxine and, 100 years later, Graf (359) showed this to be a mixture of at least seven compounds. Over 250 taxane diterpenoids are now known. Paclitaxel (312) was isolated from Taxus brevifolia (the Pacific Yew) in 1967 [360, 361] and its structure determined by X-ray crystallography in 1971 (362). The discovery of its anticancer properties led to a huge amount of research into its extraction, synthesis, production, and application. Bristol-Myers Squibb trademarked the name Taxol for paclitaxel and they, other pharmaceutical companies and academic researchers have invested much into the study of pacUtaxel and the search for active analogues and prodrugs. Some of the more significant materials in this series are shown in Fig. 8.59. 

Asao, K., lio, H., and Tokoroyama, T. (1989) Total synthesis of (+)-agelasidine C, a physiologically active marine diterpenoid with hypotaurocyamine group. Chem. Lett., 1813-1814. 

Plant products have also been detected in non-plant organisms. Morphine 1, the archetypal plant alkaloid, has in fact been shown to be a physiological plasma constituent and its production in mammals could be traced to the liver expression of the critical enzymes of its biosynthesis.17 In addition, the plant hormone abscisic acid 12 has been detected as an endogenous constituent of human brain,18 while caffeine 13 was isolated from a marine gorgonian (Paramuricea chamaelon)19 and the atisane diterpenoid serofendic acid 14, an inhibitor of the oxidant-induced mitochondrial death pathway and putative activator of mitoK(ATP) channels, has been characterised from foetal calf serum.20... 

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