Isoprene-rule diterpenes

The sesquiterpenes, diterpenes, and poly terpenes can be considered most simply from a structural point of view as products composed of multiple units of isoprene. Structures currently assigned to some of the sesquiterpenes may have to be revised as the study of terpene chemistry advances, since many of these have been based on the validity of the isoprene rule for terpene structures and exceptions to this rule are becoming known (37). 

Early studies indicated that terpenes were composed of five carbon units. By 1860, isoprene, a compound with the empirical formula C5H8, could be derived by pyrolysis of turpentine and rubber. Further, isoprene could be transformed into a C10H16 compound that subsequently decomposed back to the original five-carbon unit. Wallach recognized that terpenes could be subdivided into several groups hemiterpenes, true terpenes, sesquiterpenes, and diterpenes. In 1887, he proposed that monoterpenes (true terpenes) as well as other terpenoids were composed of isoprene units, a concept that became known as the isoprene rule (Wallach, 1887). The structure of isoprene was not solved until much later (Spurgeon and Porter, 1981). 

In contrast to the previously discussed mono-, sesqui-, and diterpenes that are biosynthesized by linear condensation of five carbon units, triterpenes arise via dimerization of two famesyl pyrophosphate units to produce an intermediate compound, squalene (1) (Fig. 23.2). Squalene (usually as the 2,3-epoxide) may then be cyclized by several mechanisms from different conformations on an enzyme surface to produce the parent skeletal types of many different kinds of triterpenes that undergo subsequent modification (Banth-orpe and Chari wood, 1980 Harrison, 1985). The structures of many triterpenes and steroids may be explained by the biogenetic isoprene rule see Chapter 18) (Connolly and Hill, 1991). 

Wallach proposed that one isoprene (2-methyl-l, 3-butadiene) unit of five carbon atoms could serve as this function. This idea was eventually elaborated on by Ruzicka and Bloch into the isoprene rule. Eventually, as we will see, the family of terpenes (Cio), sesquiterpenes (C15), diterpenes (C20), sesterpenes (C25), triter-penes (C30), and truly large compounds (polymers) found in latex and gutta-percha comprises tens of thousands of individual, unique compounds all of which may be considered as derived from isoprene (2-methyl-l,3-butadiene) and that the pair of C5 isomers, isopentenyl diphosphate and dimethylallyl diphosphate, compounds linked by interconversion (Scheme 11.41) under the influence of the isopentenyl isomerase (EC 5.3.3.1) serve as the biochemical parents to the family. ... 

Terpenes are defined and classified by the so-called isoprene rule, introduced by Wallach in 1887 [22]. Two isoprene units make one terpene unit. They are grouped according to the number of isoprene units, for example, mono terpenes [Ciol. sesquiterpenes [C15], diterpenes [C20], triterpenes [C30], and tetraterpenes [C40] contain 2, 3, 4, 6, and 8 isoprene units, respectively. A subsidiary classification is based on the number of carbon rings present in the terpene ... 

Two units of isoprene combine to form terpenes, Cjo compounds such as geraniol. Three isoprene units form sesquiterpenes, C15 compounds such as famesol. Diterpenes are C20 compotmds, triterpenes are C30 compounds, and so on. Myriad terpenoid compounds are known, and most can be traced to derivatives of isoprene as starting material. Most terpenes follow the isoprene rule, which dictates the head-to-t ul formation described earlier. AH of the terpenes shown in Figure 12.76 do not stricdy follow the pattern, but each has at least one head-to-tail connection. 

The multiples of isoprene units in a terpene serve to classify it Cio, monoterpenes C15, sesquiterpenes C20, diterpenes C30, tri-terpenes to which the steroids are closely related C25, sesterpenes. It is a curious thing to note that the isoprene rule, sound and powerfully useful not least for structure elucidation, has unnatural foundations. Isoprene (4.1) is not a naturally occurring compound. Instead the clay from which the terpenes are so orderly fashioned is isopentenyl pyrophosphate (4.14) and dimethylallyl pyrophosphate (4.15). The latter is seen in many natural compounds, e.g. (4.11) as a prenyl ... 

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