Camphor biosynthesis

Croteau, R., M. Felton, F. Karp, and R. I onaas, 1981. Relationship of camphor biosynthesis to leaf development in sage (Salvia officinalis). PlaM Ph j., 67 820-824. 

Dehal SS, Croteau R, Metabolism of monotetpenes Specificity of the dehydto-genases responsible for the biosynthesis of camphor, 3-thujone and 3-iso thujone. Arch Biochem Biophys 258 287-291, 1987. 

Dihydrocarvone [l] was treated with isopropenyl acetate in the presence of p-toluene sulphonic acid and converted into a mixture of enol acetates [2] and [3], separated by GLC Treatment of [2] with boron trifluoride in methylene chloride at room temperature for 10 minutes gave (+) Camphor [U]. This synthesis is particularly interesting in that it is a chemical analogy for the biosynthesis conversion of a monocyclic into a bi-cyclic monoterpenoid. 

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. 

Borneol, camphene, and a-pinene are made in nature from geranyl pyrophosphate. The biosynthesis of a-pinene and the related camphor is described in the chapter. In the laboratory bornyl chloride and camphene can be made from a-pinene by the reactions described below. Give mechanisms for these reactions and say whether you consider them to be biomimetic. 

Unexpected results have come to light bearing on monoterpenoid biosynthesis (Chapter 1). Banthorpe s group have shown that in the formation of the thujane and camphor skeletons, activity from labelled mevalonic acid can appear predominantly in the C5 unit supposedly derived from isopentenyl pyrophosphate and only to a minor extent in the dimethylallyl pyrophosphate-derived portion. Banthorpe has also presented evidence for a chrysanthemyl intermediate, analogous to presqualene alcohol, in the biosynthesis of artemesia ketone. 

The second reaction involves formation of the cation (the one that is not an intermediate in the first reaction), migration, and elimination. It is difficult at first to see the structure of the resulting cation so we have first drawn it deliberately badly but in the shape of the starting material. These reactions are very biomimetic as almost identical rearrangements occur in the biosynthesis of camphor and its relatives (p. 1440). 

The understanding of the degradation of natural products such as camphor has been greatly enhanced by understanding the catalytic cycle of the cytochrome P-450 enzyme P-450cam in structural detail.3,4 These enzymes catalyze the addition of 02 to nonactivated hydrocarbons at room temperatures and pressures - a reaction that requires high temperature to proceed in the absence of a catalyst. O-Methyltransferases are central to the secondary metabolic pathway of phenylpropanoid biosynthesis. The structural basis of the diverse substrate specificities of such enzymes has been studied by solving the crystal structures of chalcone O-methyltransferase and isoflavone O-methyltransferase complexed with the reaction products.5 Structures of these and other enzymes are obviously important for the development of biomimetic and thus environmentally more friendly approaches to natural product synthesis. 

Normally it is assumed that in terpenoid biosynthesis each isoprenoid unit will be equally labelled by [2- C]mevalonic acid. However, Banthorpe et al. have found that in camphor (30) biosynthesis most of the radioactivity was located at C-6. A significant size pool of dimethyl allyl pyrophosphate (5) is suggested. This... 

Fig. 9. Pathway for the biosynthesis of ( + )-camphor from geranyl pyrophosphate.

Ap fi om their intermediate role in the biosynthesis of other terpenes, little is known about the biological function of M.They are important volatile components of olfactorally active pheromone mixtures (e.g. citral, iridodiol). The bitter principle, Gen-tiopicroside (see), is also a M.In pure form or as mixtures, e.g. balsams, oil of turpentine, valtratum, camphor), M. are used widely in pharmacy, the food industry, perfumery and paint manufacture. Nerol and Geraniol are used in perfumery. 

Originally only compounds with 10 carbon atoms (monoterpenes) were considered as T, and the oxygen-containing T. were classified as camphors. According to the mechanism of biosynthesis, however, all compounds derived from active isoprene are now classified as T. or isoprenes, including steroids, carotenoids, etc. 

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