Geranyl pyrophosphate incorporation

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). 

The experiments you would want to do would include studying the incorporation of labelled (even doubly labelled) geranyl pyrophosphate and olivetol, synthesizing some of your proposed intermediates in labelled form, and seeing if they were incorporated into THC in the plant. However, attempts at these experiments have not been very successful because of poor incorporation of labelled compounds into the plant. 

H of loganin (35 R = Me). However, the first Cjo acyclic precursor must be geranyl pyrophosphate 6 n = 1) since two tritium atoms are incorporated" by the [2- C,3R,4R- H]isomer and none by the (4S)-isomer. The mechanism proposed by Arigoni for this cyclisation involves the trialdehyde (33). Potty et al. have isolated an enzyme from Citrus spp. which oxidises geraniol (27) to the corresponding aldehyde. 

The labelling pattern [ in (53)] found from the incorporation of mevalonic acid into coriamyrtin (53 R = H) and tutin (53 R = OH) are consistent with a y-curcumene origin. Both laboratories showed that the methyl and methylene groups were equally labelled, and Arigoni found significantly more radioactivity at C-12 than at the other positions. This result implies a significant pool of geranyl pyrophosphate in the plant. 

Previous results on helicobasidin (51) have suggested that y-bisabolene (54) is not a precursor. A similar conclusion has been reached for trichodermol (52) and trichothecin (53). Hanson and co-workers showed that tritium from [2- H,2- C]geranyl pyrophosphate (4 n = 1) is incorporated into all three bicyclic sesquiterpenoids. The suggested explanation is that the tritium atom is transferred by a 1,4-shift as shown in Scheme 6. The involvement of trichodiene (50) was confirmed by Machida and Nozoe. They also isolated deshydroxy-trichodermol and trichodiol A (55), which may be a precursor of the tricyclic system (see arrows). Bisabolene derivatives, as expected, were not incorporated. ... 

The direct incorporation of dimethylallyl pyrophosphate into carotenoids has not been reported. The incorporation of geranyl pyrophosphate into carotenoids has not been demonstrated either, but Varma and Chichester (1962) showed the incorporation of free geraniol into jS-carotene by carrot root slices. This result, plus those of later studies, indicate that higher plants... 

In cell-free extracts of Artemisia annua and Santolina chamaecyparissus, chrysanthemyl alcohol and its pyrophosphate are incorporated into artemisia ketone and alcohol. Artemisia alcohol (95) is converted into artemisia ketone (94) and tranj-chrysanthemic acid in the preparation from S. chamaecyparissus (Banthorpe et al., 1977a). IPP and DMAPP are incorporated into irregular monoterpenes whereas geranyl and neryl-OPP are not. An enzymatic sulf-hydryl group is involved. 

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