Cyclic diterpene

While there are a number of acyclic diterpenes such as phytol, cyclization of these acyclic diterpenes, driven by various enzymes, leads to the formation of cyclic diterpenes. A number of other biogenetic reactions, e.g. oxidation, also bring in variation among these cyclic diterpenes. 

However, various bi- and tri-cyclic diterpenes have been isolated from other Salvia species.Extraction of the leaves of 5. divinorum has now yielded a novel bicyclic diterpene, salvinorin (1), C23H28O8 whose structural elucidation forms the subject of this paper. 

The Common and Systematic Nomenclature of Cyclic Diterpenes, prepared by Rowe, J.W. Forest Products Laboratories, USDA, 1968, co-sponsored by ApSimon, J. Fetizon, M. Fujita, E. Gough, L. Hezz, W. Jefferies, P.R. Mangoni, D. Norin, T. Overton, K. Pelletier, S.W. Wenkert, E. a proposal submitted to the International Union of Pure and Applied Chemistry, Commission on Nomenclature. 

J. W. Rowe, The Common and Systematic Nomenclature of Cyclic Diterpenes, 3rd rev., pp. 40, 41,43. Forest Products Laboratory, Forest Service, U.S. Department of Agriculture, Madison, Wisconsin, 1968. 

This chapter is subdivided into sections, each based on the major skeletal types of diterpenes. A widely circulated report on the Common and Systematic Nomenclature of Cyclic Diterpenes by J. W. Rowe, contains proposals made to I.U.P.A.C. for the naming and numbering of diterpenes. Although these proposals have not yet been officially accepted, they are applied in a number of publications and have been used in the present Report. 

The nomenclature of these alkaloids is based upon the standard skeletons atisane, kaurane, and aconane with the numbering and stereochemistry illustrated. These skeletons have been incorporated into a proposal for the Common and Systematic Nomenclature of Cyclic Diterpenes which will be submitted to the lUPAC Commission on the Nomenclature of Organic Chemistry in 1969 and published in M. Fetizon and Le-Van-Thoi s forthcoming book on the cyclic diterpenes. 

Rowe, J.W., The Common and Systematic Nomenclature of Cyclic Diterpenes", 1969, Third revision. 

There are a number of branches between MVA and ent-kaurene that lead to biologically important terpenes other than the gibberellins for example, in plants, a branch at IPP leads to the side chain of cytokinins a branch at FPP leads to squalene and the sterols, also abscisic acid branches at GGPP lead to phytoene, fatty acid esters, chlorophyll esters and non-cyclic diterpenes and branches at CPF lead to (-)-trachylobane, (-f)-beyerene, ( f)-sandaracopiinaradiene (21) and ent-isokaurene (22). (For a review of the pathway to ent-kaurene see reference 23). 

Mixed coupling reactions, using two different carbonyl compounds, can be effected, but they generally lead to mixtures of products and are of limited use in synthesis. Intramolecular reactions with dicarbonyl compounds, on the other hand, provide a good route to cyclic alkenes. The keto-aldehyde 80, for example, gave the cyclic diterpene kempene-2, despite the presence of a saturated ketone... 

Figure Carbon skeletons of various cyclic diterpenes.

Approximately 5 000 naturally abundant acyclic and cyclic diterpenes derived from the parent hydrocarbon phytane are known The (3i ,7i ,ll )-enantiomer of phy-tane has been found in meteorites, oil slate, other sediments and, last but not least, in human liver. Oil slate additionally eontains (-)-(3if,7if,llif)-phytanoic acid which has also been isolated from butter. 1,3(20)-Phytadiene is one among many constituents of tobacco Nicotiana tabacum (Solanaceae) -1,3-phytadiene and its (%)-isomer are found in zooplankton. Chlorophyll in the chloroplasts of plant cells exemplifies an ester of +)-(lE,lR, l/ )-2-phyten-l-ol usually referred to as phytol. 2,6,10,14-Phytatetraene-l,19-diol, better known as plaunotol, is the ehief constituent of the leaves of flie Thai medicinal plant Croton sublyratus (Euphorbiaceae) used as "plau noi" or "kelnac" as an antiulcerative. 

Although fusicoccin is a C-25 compound, GGPP (1) is first converted to a cyclic diterpene and then modified to produce fusicoccin (West, 1981). This compound is similar in some regards to the ophiobolanes (see the section Sesterterpenes, below) (Stoessl, 1981). 

Robinson, D. R. and C. A. West, Biosynthesis of cyclic diterpenes in extracts from seedlings of Ricinus communis L. II. Conversion of geranylgeranyl pyrophosphate into diterpene hydrocarbons and partial purification of the cyclization enzymes. Biochemistry, 9, 80-89 (1970). 

Extracts of several spices, particularly of sage and rosemary, have the ability to prevent the autoxida-tion of unsaturated triacylglycerols. Among the most effective antioxidant constituents of both spices, the cyclic diterpene diphenols, camoso-lic acid (XXXIII in formula 22.9) and camosol (XXXIV) have been identified. 

Mohan, R.S., Yee, N.K.N., Coates, R.M. etal, (1996) Biosynthesis of cyclic diterpene hydrocarbons in rice cell suspensions conversion of 9,10-s/n-labda-8( 17),13-dienyl diphosphate to 9P-pimara-7,15-diene and stemar-13-ene. Arch. Biochem. Biophys., 330, 33-47. 

Fig. 2. The MVA biosynthetic pathway leading to the cyclic diterpene, ent-kaurene. GAj 2" ldehyde is the common precursor for all known gibberellins (now numbering 72). (Figure from Phinney, ).

GGPP is a key branch point metabolite of polyisoprenoid metabolism. Apart from the cyclic diterpenes, it is the precursor of the tetraterpenes (carotenes, xanthophylls), and acyclic diterpenes (phytol). Cyclic diterpenes compete with compounds of established importance for either GGPP or its precursors (e.g., famesyl pyrophosphate). The spotty nature of resin diterpene distribution may in part be explained by the obvious demand for carotenoids and phytyls and the relatively unestablished requirement for these nongibberellin diterpenes. 

Figure 3. Linear and Cyclic Diterpene Skeletal Types... 

Figure 3. Linear diterpene skeletal types and cyclic diterpene skeletal types derived from normal and e iMabdane precursors.

Thirty-nine diterpenes from frontal glands of termites are listed by Wheeler and Duffield in Handbook of Natural Pesticides Vol. IVB, Pheromones (ed. Morgan and Mandava, CRC Press, Boca Raton, 1985, pp. 159), more have been isolated since. It is clear these are insect-produced via the isoprenoid route. When the soldiers of Nasutitermes octopilis were injected with C-labelled acetic acid or mevalonolactone, the C was incorporated into tri- and tetra-cyclic diterpenes (Prestwich, Jones and Collins, Insect Biochemistry, 1981,11, 331). 

Figure 7.3 Some cyclic diterpenes from termites. Cembrene is shown with its isopropenyl group turned inwards. Rearrangement as indicated may lead to bicyclic seconervitenes, tricyclic nervitenes and tetracyclic kempenes. Oxygenated examples of each type are given. The tetrapropionate is a homoditerpene...

Diterpenes are a large group of C20 compounds. Their main structural types are acyclic compounds, cyclic compounds, bicyclic diterpenes and tri- and tetra-cyclic diterpenes. The cosmetic use of this group of compounds is restricted to the antioxidant properties of the phenolic diterpenes extracted from rosemary and sage. 

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