Clerodanes

Tokoroyama T. Synthesis of Clerodane Diterpenoids and Related Compounds -Stereoselective Construction of the DecaUn Skeleton With Multiple Contiguous Stereogenic Centers Synthesis 2000 611-633... 

Demetzos, C. and Perdetzoglou, D. 2002. Diurnal and seasonal variation of the essential oil labdanes and clerodanes from Cistus monspeliensis L. leaves. Biochem. Syst. Ecol. 30 189-203. 

Januario AH, Simone LS, Silvana M, et al. Neo-clerodane diterpenoid, a new metallo-protease snake venom inhibitor from Baccharis trimera (Asteraceae) anti-proteolytic and anti-hemorrhagic properties. Chem Biol Interact 2002 150 243-251. 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

Bioassay-directed isolation of antifungal compounds from the bark of Macaranga monandrayie ( eA. two clerodane-type diterpenes, kolavenic acid and 2-oxo-kolavenic acid, with moderate activity against Phomopsis viticola... 

Bicyclic diterpenes-clerodanes. An important group of Insect antifeedants are the clerodane diterpenoids, which have been isolated from several different plant families (13)(Figure 1). Particularly well studied are the antifeedant activities of caryoptln and clerodin, and their derivatives, from Clerodendron and Caryopteris, Verbenaceae, against the tobacco cutworm Spodoptera litura L. (25-27). 

Two chlorine-containing clerodanes, tafricanlns A and B, with similar antifeedant properties, have been isolated from a South African bush, Teucrium africanum (32). Teucjaponln B, from Teucrlum japonlcum, is also inhibitory to the feeding of Spodoptera litura... 

Belles al. have recently discussed the structure-activity relationships of several natural clerodane diterpenoids and their derivatives, and have compared their activity with that of some synthetic butenollde derivatives (34). 

Figure 1. Clerodanes with insect antifeedant activity.

Solldago is a mostly North American genus of about 125 species. It belongs to the Asteraceae (Compositae), a family with a very distinctive chemistry (57, 58). The genus itself contains several different classes of secondary compounds including a number of diterpenes (59). During the 1960 s and 1970 s Anthonsen in Finland, and McCrindle and his coworkers in Canada, isolated about twenty-five different compounds from the roots of Solidago species, mainly clerodanes and labdanes. But in the last five years attention has turned to the aerial parts of the plant and compounds of several other classes of diterpenes, abietanes and kauranes, have been isolated (60-79) (Table II). 

Clerodanes.—In a study of South African Macowania species, a cis-clerodane acid (28) and labdanolic acid were obtained from M. glandulosa. Deoxymarrubialac-tone (29) has been isolated from Chaiturus marrubiastrum. Linarienone (30) is another ds-fused clerodane which has been obtained from the roots of Linaria japonica (Scrophulariaceae) and correlated with linaridial. The bacchotricuneatins A (31) and B (32) are two new diterpenoid lactones which were isolated from Baccharis tricuneata (Astereae) and whose structures were determined by a combination of spectra and X-ray analysis. 

Mar. ISOPR. Ditero. cleistanthene and clerodane. SHKIM. cinnamic acids. Mar. low Mar. low... 

Esquivel, G., Calderon, J.S., and Elores, E., A neo-clerodane diterpenoid from Scutellaria seleri-ana, Phytochemistry, 47, 135, 1998. 

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. 

The copper-catalyzed conjugate addition of methyhnagnesium iodide to cyclohexenone and trapping of the resulting enolate as its trimethylsilyl enolate, followed by TrSbCle-catalyzed Mukaiyama reaction, are the first steps of an elegant synthesis of enantiomeri-caUy pure clerodanes (equation 45). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

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],... 

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