Isoprene, coupling Pyrophosphate

In similar fashions, the core pathway up to C25 compounds (five isoprene units) is formed by sequential addition of C5 moieties derived from IPP to a starter unit derived from DMAPP. Thus, sesquiterpenes are formed form the precursor 2E, hS-farnesyl pyrophosphate (FPP), and diterpenes from 2E, 6E, IO -geranylgeranyl pyrophosphate (GGPP). The parents of triterpenes and tetraterpenes are formed by reductive coupling of two FPPs or GGPPs, respectively. Rubbers and other polyisoprenoids are produced from repeated additions of C5 units to the starter unit GGPP. 

Continuation of the head-to-tail addition of five-carbon units to geranyl (or neryl) pyrophosphate can proceed in the same way to farnesyl pyrophosphate and so to gutta-percha (or natural rubber). At some stage, a new process must be involved because, although many isoprenoid compounds are head-to-tail type polymers of isoprene, others, such as squalene, lycopene, and /3- and y-carotene (Table 30-1), are formed differently. Squalene, for example, has a structure formed from head-to-head reductive coupling of two farnesyl pyrophosphates ... 

Prostaglandins and terpenes are still other classes of lipids. Prostaglandins, which are found in all body tissues, have a wide range of physiological actions. Terpenes arc often isolated from the essential oils of plants. They have an immense diversity of structure and are produced biosynthetically by head-to-tail coupling of two five-carbon isoprene equivalents —isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

The activated derivative of isoprene pyrophosphate (IPP), as noted in the Introduction, comprises the five-carbon starting synthon for a host of hydrocarbon-Uke compounds that occur in both animals and plants. The term terpene is customarily used to denote the class of compounds made up of two isoprenes. Triterpene thus comprises compounds built from six isoprenes or 30 carbon atoms. That leads to an enormous number of possible structures since there are few restraints on the manner in which IPP couples. Literally hundreds of 30-carbon triterpene natural products have thus been isolated and characterized. Only one member of that group, lanosterol (4-1), is relevant to this discussion of steroids. 

As a general rule, natural products derived from isoprenoid units arise from head-to-tail reactions of that synthon. The majority of the structures of such products built up by condensation of IPP will as a result display a branched methyl on every fifth atom in the chain. Thus, reaction of IPP (1-5) with the isomer with the internal double bond (1-6) proceeds by head-to-tail coupling with expulsion of a pyrophosphate ion. The free alcohol from the product 2-1 (Scheme 2.2) is the fragrant terpene geraniol. Reaction of 2-1 with a second isoprene unit in this case again takes place by head-to-tail reaction to afford 2-2. The free alcohol from this 15-carbon triene is known as farnesol and is generally classed as a sesquiterpene (Latin sesqui-, one and a half). The molecule is displayed in the unlikely conformation 2-2b, in anticipation of the next reaction. 

There is an extraordinarily important class of molecules called steroids. The carbon framework common to all steroids is three cyclohexanes and a cyclopentane fused together (Fig. 12.77).This arrangement is often referred to as three rooms and a bath. Steroids are formed in Nature from isoprene units. We will start our summary of the biosynthesis with two units of farnesyl pyrophosphate, which can be enzymatically coupled in a tail-to-tail fashion to give the symmetrical triterpene called squalene (Fig. 12.78). 

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