Biogenetic isoprene rule

Battersby and Co-workers (25-28), Money et al (29) and Leete et al (30) all reported the specific incorporation of [2- C] mevalonic acid and [2- C] geraniol into representative examples of the corynanthe, aspidosperma and iboga groups of alkaloids, and in each case the distribution of radioactivity was in full agreement with the monoterpene hypothesis developed by Thomas (23) and Wenkert (2U), and according to the biogenetic isoprene rule that monoterpene are formed in nature by suitable modification of geranyl pyrophosphate (31). 

Isoprene rule. In the light of the fact that the then known mono- and sesquiterpenes were built up of two or three isoprene units, respectively, O. Wallach in 1887 prtmosed his simple isoprene rule . In 1953 L. Ruzicka formulated his biogenetic isoprene rule which proved to be a milestone in the chemistry of the terpenoids. According to this rule, all terpenoids are derived from acyclic parent structures monoterpenes are formed from geranyl pyrophosphate (GPP, Cio), sesquiterpenes from famesyl pyrophosphate (FPP,... 

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). 

The isoprene rule (337) and its evolved version, the biogenetic isoprene rule (336, 337), have proven to be of fundamental consequence in the development of terpene chemistry. According to the biogenetic isoprene rule, which was formally enunciated by Ruzicka in 1953, terpene structures may be rationalized, or preliminary structures deduced, by accepted reaction mechanisms from hypothesized acyclic precursors such as geraniol, farnesol, geranylgeraniol, etc. Biosynthetic investigations (20, 75, 87, 100, 110, 160, 162, 179, 263) over the past three decades have fully confirmed the biogenetic isoprene rule, and have provided detailed information on several fundamental steps in isoprenoid biosynthesis. 

According to the biogenetic isoprene rule, sesquiterpenes arise from a linear precursor such as farnesol. There is considerable biosynthetic evidence to support this, and farnesyl pyrophosphate is considered as the immediate biosynthetic precursor of almost all sesquiterpenoids (110, 263). Conceptually, cyclization of farnesyl pyrophosphate can proceed from either the tail end (by ionization of the pyrophosphate moiety) or the head (by a or OH" attack on A ), Both... 

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