Diterpenoids discovery

Since the discovery of the high anticancer activity of taxol, much attention has been drawn to its asymmetric synthesis. The total synthesis stood for more than 20 years as a challenge for organic chemists. The compound taxoids are diterpenoids isolated from Taxus species and have a highly oxidized tricyclic carbon framework consisting of a central eight-membered and two peripheral six-membered rings (see Fig. 7-2).21... 

The discovery of a potent and selective K-opioid receptor agonist compound, salvinorin A (54), a hallucinogenic neoclerodane diterpenoid from Salvia divinorum Epling and Jativa, has created particular interest in recent years, since it is the first nonnitrogenous compound found to demonstrate this type of activity. 

This discovery of diterpenoids in this species roused the interest for the genus, especially of researchers in Canary Islands (Tenerife) and Spain (Madrid and Granada) many indigenous species were collected and studied and a considerable number of papers were published. 

The naturally occurring diterpenoids with the taxane skeleton are the typical constituents of 7ax s. The constituents of the yew became the active subject of phytochemical and synthetic work since the discovery of terpenes belonging to the taxane group (8-10). 

The discovery of the novel diterpenoid anticancer agent taxol in 1971 by Monroe Wall and his collaborators ranks in retrospect as one of the most significant discoveries ever made in the field of naturally occurring anticancer agents. Although extensive researches have been done on natural anticancer agents, only a handful of plant-derived natural products have been found to show clinically useful activity, and taxol is clearly a member of this group. 

Diterpenoids constitute the second largest class of terpenoids with over 2200 compounds belonging to some 130 distinct skeletal types. The discovery of new types and new members has been most dramatic during the past decade, mostly as a result of screening of marine flora and fauna (89, 144, 397). Figure 8.1.17 lists diterpene types relevant to our present discussion. An essentially complete list will be found elsewhere (378). 

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. 

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