Cyclization of geranyl pyrophosphate

Croteau, R. B. In Flavor Precursors Teranishi, R. Takeoka, G. R. Guntert, M., Eds. Monoterpene Biosynthesis cyclization of geranyl pyrophosphate to (+)-sabinene Amercian Chemicd Society Symposium Seriers 490 Washington, DC, 1991, pp. 8-20. 

Croteau, R., Felton, M. and Ronald, R.C. (1980b) Biosynthesis of monoterpenes preliminary characterization of /-encfo-fenchol synthetase from fennel (Foeniculum vulgare) and evidence that no free intermediate is involved in the cyclization of geranyl pyrophosphate to the rearranged product. Archives of Biochemistry and Biophysics 200(2), 534-546. 

With the preceding reviews of the enzymology of monoterpene cyclization and of model studies relevant to the cyclization process, it is possible to formulate a unified stereochemical scheme for the enzymatic cyclization of geranyl pyrophosphate (Figure 4). The proposal which follows is consistent with the implications of parallel advances in related fields, most notably the contributions of Cane (8,16,24,25,52), Arigoni (67) and Coates (68,69) on the stereochemistry of sesquiterpene and diterpene cyclizations, and of Poulter and Rilling (29,70) on the stepwise, ionic mechanism of prenyl transferase, a reaction type of which several monoterpene, sesquiterpene and diterpene cyclizations are, in a sense, the intramolecular equivalents. 

Because the coupled isomerization-cyclization of geranyl pyrophosphate proceeds without detectable free intermediates, no ready means has been available to examine the isomerization to linalyl pyrophosphate in isolation. In an attempt to dissect the normally cryptic isomerization step from the tightly coupled reaction sequence, a non-cyclizable analog of geranyl... 

Figure 8. Sulfonium ion analogs of the linalyl (I) and o-terpinyl (II) carbonium ion intermediates in the cyclization of geranyl pyrophosphate to (+)-bornyl pyrophosphate (III) and (+)-a-pinene (IV).

Cyclase preparations have been obtained which catalyze the cyclization of geranyl pyrophosphate to essentially all major structural classes of monoterpenes. These cyclases are membrane bound in the synthesizing cells, but are readily solubilized (Charlwood and Charlwood, 1991a Croteau, 1987). 

The formation of oxygenated derivatives usually involves oxygenation of the parental hydrocarbons. The essential oil of Artemisia absinthum contains /-sabinyl acetate (42%) (20), geranyl pyrophosphate with a soluble enzyme, is the key cyclic precursor of 3-thujone and other C-3-oxygenated... 

Croteau R (1992) Biosynthesis of thujane monoterpenes. In Hopp R,Mori K (eds) Recent developments in flavor and fragrance chemistry. VCH, Weinheim Germany, p 263 Croteau R (1992) Monoterpene biosynthesis cyclization of geranyl pyrophosphate to (+)-sabinene. In Teranishi R, Takeoka GR, Guntert M (eds) Flavor precursors thermal and enzymatic conversions. American Chemical Society, Washington DC, ACS Symp Series 490, p 8... 

Gambliel, H. and Croteau, R. (1984) PineneCyclase-I and Cyclase-II. Two enzymes from sage (Su/via officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. /. Biol Chem., 259, 740-748. 

Fig. 3. Stereochemical scheme for the enzymatic cyclization of geranyl pyrophosphate (GPP) to bornyl pyrophosphate (BPP) via linalyl pyrophosphate (LPP).

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