Diterpenoids biological activity

Diterpenoids have a wide range of biological activities. Their role in plant-insect interactions, both as antifeedants and growth inhibitors, is reviewed. Four ent-kauranes, kaur-16-en-19-oic acid, (-)-kauran-l > -ol, 15 t-hydroxy-(-)-kaur-16-en-19-oic acid, and 17-hydroxy-(-)-kaur-15-en-19-oic acid, have recently been isolated from the leaves of Solidago nemoralis.These compounds were found to have antifeedant activity against Trirhabda canadensis. 

The diterpenoids of Isodon (Labiatae) species have been reviewed. The presence of an a-methylenecyclopentanone moiety in these diterpenoids is important for their anti-tumour and anti-bacterial activity. " Inflexin (79) is a cytotoxin and insect antifeedant which has been isolated from Isodon inflexus. Isodomedin (80) is another member of this series, isolated from /. shikokianus, which shows this type of biological activity. Its structure was assigned on the basis of its H and C n.m.r. spectra and on an interrelationship with kamebanin (81), isolated from /. kameba. 

Carbon-13 NMR studies of the biologically active nor-diterpenoid dilactones from Podocarpus plants. Hayashi, Y. Matsumoto, T. Uemura, M. Koreeda, M. Org. Magn. Resort. 1980,14,86-91... 

The genus Consolida, Aconitum, and Delphinium (Ranunculaceae) are well-known to be rich in diterpene alkaloids, which possess a diverse range of biological activities. These plants have also been the cause of poisonings, which primarily occur in cattle as well as human beings, due to toxicity of their alkaloids. In one of our recent studies, five diterpenoid-derivative alkaloids, lycoctonine (9), 18-O-methyllycoctonine (10), delcosine (11), 14-acetyldelcosine (12), and 14-acetylbrowniine (13) (as shown in Fig. 3) were screened for their antibacterial, antifungal, and antiviral activities [39]. 

In view of the biological activity of taxodione, some attention has been directed at the introduction of a C-6 carbonyl group. The nor-abietatetraene (56) was converted52 into a cis-glycol which on reaction with formic acid gave the C-6 ketone. As an alternative sequence, hydroboronation and oxidation also gave a C-6 ketone. The photosensitized oxidation of 6,7-dehydro-aromatic diterpenoids [e.g. (57)] has also been studied53 with this objective. However, the products were unsaturated ketones [e.g. (58)]. 

The range of biological activity that has been recorded for 14-membered-ring diterpenoids is remarkably wide They were found to function as insect trail pheromones, termite allomones, neurotoxins, cytotoxins, and anti-inflammatory and antimitotic agents. 

To show how this is done in practice, we will examine Nicolaou s synthesis of zoopatenol 212, a biologically active natural diterpenoid (Scheme 2.91). A retrosynthetic analysis of this structure envisions the disconnection of bonds a, b, and c, to lead to rather simple precursors, the bromo ketone 213 and the triol 214. A formal pathway for the assemblage of 212 from these precursors involves several steps, as outlined in Scheme 2.91. This plan appears strategically... 

The MEP pathway is the starting material of major plant terpenoids of economic value e.g., monoterpenes from essential oils, diterpenoids with potent biologic activity (taxol, ginkgolides), vitamins (tocopherol), or vitamin precursors (carotenoids). The first attempts to overexpress some of its genes (especially dxs or dxr) led to enhanced carotenoid production in tomato (18) or monoterpenes in mint (19). 

Diterpenoids are the most important compounds responsible of the biological activities found in numerous Salvia species. Antituberculous effects have been established for S. blepharochlyna [5], S. multicaulis also reported for it s antifungic effect [6] and S. prionitis which possess antiphlogistic and antibacterial properties [7,8] beside its antituberculous activity. 

The biological activity of the diterpenoids of the aphidicolin-stemodin series makes these compounds attractive targets. The total synthesis of stemodin (96) has been described.172 The key spiro-centre at C-9 was constructed by the internal aldol condensation of the keto-aldehyde (97) to afford (98). Several stereoselective syntheses of aphidicolin have been reported with different solutions to the problem... 

If there is already a chiral centre in the molecule that has already been controlled by asymmetric synthesis, the AE reaction will ignore it if it is far enough away. Yamada s synthesis10 of the biologically active diterpenoid 45 illustrates this and demonstrates control when nucleophiles attack an unsymmetrical epoxide. Preliminary disconnections with a Diels-Alder in mind took the chemists back to the diol 48. 

The number of known diterpenoids continues to increase although chemical studies and transformations of the various skeleta have diminished. During the year a number of novel skeletal types have been described, particularly in isolates from termites and marine organisms. The range of biological activities exhibited by the diterpenoids has attracted some attention. 

Some further aspects of the chemistry and biological activity of the insecticidal substances cinnzeylanine and cinnzeylanol have been described. The labelling pattern of colletotrichin (129), biosynthesized from [1- C]- and [1,2- C2]-acetate, has been examined and indicates that it is a nor-diterpenoid with an additional y-pyrone ring. 

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