Bornyl pyrophosphate

BORN-OPPENHEIMER APPROXiMATION ADIABATIC PHOTOREACTION DIABATIC PHOTOREACTION BORNYL PYROPHOSPHATE SYNTHASE BOROHYDRIDE REDUCTION ACYL-PHOSPHATE INTERMEDIATE BOSE-EINSTEIN CONDENSATE Bound water,... 

BORNYL PYROPHOSPHATE SYNTHASE Geranyl diphosphate synthase,... 

Curiously, certain cyclases, notably (+)-bornyl pyrophosphate cyclase and (-)-endo-fenchol cyclase, are capable of cyclizing, at relatively slow rates, the 3S-linalyl pyrophosphate enantiomer to the respective antipodal products, (-)-bornyl pyrophosphate and (+)-endo-fenchol (74,75). Since both (+)-bornyl pyrophosphate cyclase and (-)-endo-fenchol cyclase produce the designated products in optically pure form from geranyl, neryl and 3R-linalyl pyrophosphate, the antipodal cyclizations of the 3S-linalyl enantiomer are clearly abnormal and indicate the inability to completely discriminate between the similar overall hydrophobic/hydrophilic profiles presented by the linalyl enantiomers in their approach from solution. The anomalous cyclization of the 3S-enantiomer by fenchol cyclase is accompanied by some loss of normal regiochemical control, since aberrant terminations at the acyclic, monocyclic and bicyclic stages of the cationic cyclization cascade are also observed (74). The absolute configurations of these abnormal co-products have yet to be examined. 

Figure 5. Stereochemistry at Cl of geranyl pyrophosphate and neryl pyrophosphate in the cyclization, via linalyl pyrophosphate, to bornyl pyrophosphate. "Reproduced with permission from Ref. 76. Copyright 1985, Journal of Biological Chemistry".

The availability of the bornyl pyrophosphate cyclases has provided a unique opportunity to directly examine the function... 

Figure 6. Conversion of 6,7-dihydrogeranyl pyrophosphate, via 6,7-dihydrolinalyl pyrophosphate, to dihydro olefins and alcohols by (+)-bornyl pyrophosphate and (+)-pinene cyclases.

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).

In the Figures, GPP indicates geranyl pyrophosphate, NPP indicates neryl pyrophosphate, LPP indicates linalyl pyrophosphate, and BPP indicates bornyl pyrophosphate. 

Cineol, fenchol (the alcohol corresponding to fenchone), y-terpinene and bornyl pyrophosphate, for instance, are built from geranyl pyrophosphate and/or neryl pyrophosphate by polyfunctional enzyme proteins, the so-called carbo-cyclases. No free diffusable intermediates occur. 

The reactions are late steps in the biosynthetic pathway. Thymol, for instance, is formed from y-terpinene via p-cymene, camphor from bornyl pyrophosphate via borneol (Fig. 100). Menthol is derived from piperitenone as shown in Fig. 101. Terpinyl acetate and linalyl acetate are esters of with acetic acid, respectively. 

Bornyl pyrophosphate synthase 2 phosphatase 3 bomeol dehydrogenase... 

Croteau R, Karp F 1979 Biosynthesis of monoterpenes preliminary characterization of bornyl pyrophosphate synthetase from sage Salvia officinalis) and demonstration that geranyl pyrophosphate is the preferred substrate for cyclization. Arch Biochem Biophys 198 512-522... 

Figure 3.11 shows the biosynthesis of (+)-bornyl pyrophosphate (the precursor of (-l-)-borneol (28) and (+)-camphor (29)) and of (+)-sabinene (30) (the precursor of the thujones) from 3R)-20 cyclized in an anti,endo conformation (Wise et al. 1998). Other related products include camphene (31) and 1,8-cineole (32). The chemistry involved in the formation of the final products includes Wagner-Meerwein rearrangements of hydride and (in the case of camphene) a skeletal carbon-carbon bond as well as simple cyclizations. The biosynthesis of (-)-a-and P-pinene (33 and 34) proceeds along similar lines from (3S)-20 and is shown in Figure 3.12. 

The labeling patterns of antipodal bornane and plnane monoterpenes derived from [l- H]geranyl pyrophosphate by partially purified cyclases have recently been determined [(+)- and (-)-bornyl pyrophosphate are labeled at C3, and (+)- and (-)-pinenes at C7].22 2ii These results indicate that the antipodes are derived via enantiomeric cyclizations Involving antipodal linalyl and a-terpinyl intermediates, rather than by... 

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

In examining conformational questions in the bortiyl cyclizations, lR-1- H 2- C- and 1 -1- H 2- C-labeled geranyl pyrophosphates were separately converted to (+)-bornyl pyrophosphate and (-)-bornyl pyrophosphate by partially purified preparations from S. officinalis and T. vulgare, respectively. Each pyrophosphate ester was hydrolyzed, and the resulting borneol was oxidized to camphor (Fig. 4). The stereochemistry at C3 of the derived ketone (corresponding to Cl of the acyclic precursor)... 

Saito, and C. Chang, Mechanism of the pyrophosphate migration in the enzymatic cyclization of geranyl and llnalyl pyrophosphates to (+)-and (-)-bornyl pyrophosphates. Biochemistry 24 7077 (1985). 

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