Monoterpenoids from Geranyl Pyrophosphate

Carbocations are, of course, electron-deficient species and will therefore seek out electron-rich centres with which to react. In the 

The ring strain at this point in the biosynthesis can also be relieved by means of a Wagner-Meerwein rearrangement (see Chapter 5 for details of this reaction) to produce the much less strained fenchane system. Addition of water, followed by oxidation, gives the ketone, fenchone. 

Similarly, the bornyl carbocation (2.17) can react with water to give borneol and this can be oxidised to camphor, the characteristic odorant of camphor wood. The isocamphane skeleton is formed by a Wagner-Meerwein rearrangement of the bornyl carbocation. 

SESQUITERPENOIDS FROM CIS, TRA 7VS-F ARNES YL PYROPHOSPHATE WITH INITIAL CLOSURE AT THE 6,7-DOUBLE BOND 

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Bxe enzymology of monoterpene biosynthesis has been extensively studied particularly in Salvia species. Systems have been obtained which mediate the formation of mono- and bicyclic monoterpenoids from geranyl pyrophosphate. Not unexpectedly the key enzyme systems are at their most active during maximum... 

The commonest bicyclic monoterpenoid skeleta are shown in Figure 5.1. The bicyclic monoterpenoids are all formed from geranyl pyrophosphate... 

Myrcene (32) is also koown as p-myrcene and its systematic name is 7-methyl-3-methylene-l,6-octadiene. It is very widespread in nature. This is not surprising as it is formed in nature by elimination from geranyl pyrophosphate, the precursor of all monoterpenoids. It can also be formed by elimination of water from alcohols such as geraniol or linalool, and so its presence in namral extracts may be as an artifact (formed during the extraction process) rather than as a genuine plant metabolite. 

The biosynthesis of monoterpenoids and camphor has been described by several authors (108-llU). Ruzicka (115,116) proposed a unified biogenetic scheme for terpenes. The biosynthetic building blocks for these terpenes are iso-prene units. The biosynthetically active isoprene units are isopentenyl pyrophosphate [l] and dimethyl allyl pyrophosphate [2] the compounds that are derived from acetate via mevalonic acid (Scheme V). Geranyl pyrophosphate [3] is the C-10 precursor for the terpenes (117). Banthorpe and Baxendale (ll8) confirmed the biosynthetic pathway of (iamphor via acetate mevalonate by conducting degradation study of camphor, biosynthesized from l c labelled mevalonic acid. The biosynthesis of camphor is summarised in Scheme VI. 

The defence secretion of the milliped Polyzonium rosalbum contains the spiro-monoterpenoid polyzonimine (35) 97 the isolation of the spirocyclic nitro-compound (36)98 might suggest a non-geranyl pyrophosphate biogenetic route from a pyr-rolizidine alkaloid. The production of verbenone in the bark beetle Dendroctonus sp. may be associated with chemical communication.99... 

A problem in the use of dimethylallyl pyrophosphate (3) is its instability. In a study of this problem the half-life of this substance was examined over a range of pH values and temperatures. Both cis- and trans-prenyl pyrophosphates (4 n = 0, 1, or 2) occur in Pinus radiata. Their biosynthesis from [2- C,3R,4K- H]-mevalonic acid proceeded with retention of tritium whereas with [2- C,3K,4S- HJmevalonic acid tritium was lost [except in the case of isopentenyl pyrophosphate (4 n = 0)]. The authors suggest that since they could not detect an isomerase, there may be a cis- and a trans-prenyl transferase both of which eliminate the label derived from [4S- H]mevalonic acid. However, compart-mentalization may have resulted in the isomerase not being available to the administered monoterpenoids, although it may act on geranyl pyrophosphate formed in situ. The absence of 6-cis-famesol derivatives tends to support this idea. Further work on this system again produced no evidence for isomerization or metabolism of [l- H]nerol pyrophosphate to 2-rrans-6-c(s-farnesyl pyrophosphate. 

Terpenes are synthesised in organisms by complex mechanisms from isoprene units, isopentenyl phosphate and dimethy-lallyl diphosphate (pyrophosphate). The first product is geranyl diphosphate, which is the universal precursor of monoterpenoids. The reaction of geranyl diphosphate with another molecule of isopentenyl diphosphate yields famesyl diphosphate, which is the precursor of sesquiterpenoids. Further reaction with isopentenyl diphosphate gives geranylgeranyl diphosphate, the precursor of diterpenoids (see Figure 3.10). 

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