Clerodane diterpene

Akaike, S. et al., A new ent-clerodane diterpene from the aerial parts of Baccharis gaudichaudiana, Chem. Pharm. Bull, 51, 197, 2003. 

Tojo, E. et al., Clerodane diterpenes from Haplopappus deserticola. Phytochemistry, 52, 1531, 1999. 

Phytochemical studies of these species led to the isolation and structural characterization, by NMR and MS analysis, of many secondary metabolites, mainly flavonoids, and expecially flavonol glycosides, clerodane diterpenes, and triterpenes having the lupane, ursane, and oleanane skeletons. Particularly flavonoids and their glycosides have a chemotaxonomic interest in the genus and in general in the Chrysobalanaceae family. 

In the course of our phytochemical work we studied seven Licania species all belonging to Venezuelan flora, collected in Puerto Ayacucho, Estado Amazonas and in the Parque Nacional Henry Pittieri, Maracay, Estado Aragua. A number of new and known secondary metabolites, mainly flavonoids, especially flavonol glycosides, sterols, and triterpenes having the lupane, ursane, and oleanane skeleton were isolated and characterized. The last part of this chapter deals also with the isolation of clerodane diterpenes from the methanol extract of L. intrapetiolaris by Oberlies et al., 2001 [4]. All the Licania species investigated up to now are reported in Table 1. 

Finally, the triterpenoid cucurbitacin B, isolated from L. intrapetiolaris, showed activity in the KB (human oral epidermoid carcinoma) assay with EC50 value of 0.008 pg/ml. The clerodane diterpenes intrapetacin A and intrapetacin B displayed moderate activity vs KB as well [4],... 

The Brazilian plant Vellozia bicolor contains the isopimarane diterpene 12-chloroillifunone C (436). The corresponding epoxide, which is also found in this plant, is not converted to 436 under the isolation conditions (623). Teuracemin (437), a novel weo-clerodane diterpene, was isolated from Teucrium racemosum and is the 7-hydroxy derivative of the known tafricanin A (624). Examination of fresh plant material revealed the presence of 437. The new weo-clerodane ajugarin-I chlorohydrin (438) has been characterized from the Indian plant Ajuga parviflora... 

Salah, A. M., Bedir, E., Ngeh, T. J., Kahn, I. A., Wedge, D.E. Antifungal clerodane diterpenes from Macaranga monandra (L.) Muell. Et Arg. (Euphorbiaceae). J Agric Food Chem2003 51 7607-7610. 

Fig. (19). Neo-clerodane diterpenes from Linaria saxatilis var. glutinosa.

The clerodanes are a notable example of feeding deterrents2 and further examples have been discovered recently. The natural insect antifeedant clerodin (100) forms the basis of the name of this type of diterpenes called the neo-clerodane diterpenes. Ateo-clerodanes are compounds with a clerodane skeleton and exactly the same absolute configuration as clerodin. Those that have the opposite absolute configuration are referred to as ent-neo- cl erod an es. 

Ajugarin I (clerodane diterpene) Ajuga remota (Lamiaceae) Insect antifeedant... 

Caryoptin (clerodane diterpene) Caryopteris dioarkata (Verbenaceae) Antifeedant (bitter)... 

In 1962, the AC of clerodin 7,32 a key compound of the clerodane diterpenes, was determined as shown in Figure 12 by the X-ray Bijvoet method.33 Since this AC was believed to be correct, clerodin 7 was then treated as a reference compound for newly isolated members of this diterpene family. For example, in 1974, the ACs of caryoptin 8 and 3-epicary op tin 9 were determined to be as shown by CD and/or chemical correlation with 7. 

Figure 12 The absolute configurations of clerodane diterpenes as determined by X-ray crystallography/CD/chemical correlation. However, the ACs of compounds in brackets were later reversed.

To date more than 100 species from the large genus Baccharis have been investigated chemically. The most widespread compounds are clerodane diterpene derivatives, but labdane derivatives have also been isolated. Furthermore, typical acetylenic compounds, baccharis oxide, a unique triterpene, and derivatives of hydroxyacetophenone are present, although it is mainly other biologically active constituents, e.g. flavonoids, sesquiterpenes and essential oils that have been reported in the last years. The constituents of Baccharis species compiled from different sources are presented below. 

Tortoriello and Aguilar-Santamaria [120] investigated in detail the spasmolytic mechanisms of action of one of these plants, B. serraefolia. The results suggest that the extract does not interact with classical receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intracellular store. Different chemical compounds, such as clerodane diterpenes and flavonoids, which are typical constituents from the Baccharis genus, have been considered as the active principles of many spasmolytic drugs. A bioassay-monitored fractionation of an extract from B. genistelloides yielded a mixture that blocked the calcium-induced contractions of KCl-depolarized rat portal vein preparations [121], Pharmacological tests of two pure compounds isolated from the mixture revealed a dilactonic clerodane-diterpene, Fig. (70) as the active compound. 

Fig (70). Structure of an spasmolytic clerodane-diterpene isolated from Baccharis genistelloides... 

Khan et al. (11) used a Chromatotron CPTLC apparatus in the separation of some unusual clerodane diterpenes (e.g.. Compound 5) in a chemotaxonomic study of the flacourtiaceous species Zuelania guidonia. Silica gel sorbent and a... 

Khan, M. R., Gray, A 1., and Waterman, P. G. (1990) Clerodane diterpenes from Zuelania guidonia stem bark Phytochemistry 29, 2939-2942. 

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