Clerodane Diterpenoids Research Articles

Responses of Spodoptera littoralis larvae to Tunisian plant extracts and to neo-clerodane diterpenoids isolated from Ajuga pseudoiva leaves

Thirteen plants growing in Tunisia were tested against Spodoptera littoralis larvae. From the acetone extract of Ajuga pseudoiva leaves, showing interesting antifeedant activity, three new ( 1–3) and two known ( 4–5) active clerodane diterpenoids were isolated following a bioassay-guided chromatography.

Synthesis of Clerodane Diterpenoids and Related Compounds - Stereoselective Construction of the Decalin Skeleton with Multiple Contiguous Stereogenic Centers

Stereoselective construction of contiguous stereogenic centers in the decalin ring - usually four - is central to the synthesis of clerodane diterpenoids and the present review surveys the methods utilized to meet this task. Major strategies for the stereocontrol are: (i) diastereoface-selective reactions on a rigid ring, (ii) conformational preference of a rigid ring structure in an equilibrium condition, and (iii) diastereoselective cyclization. According to the classification based on the methods for construction of the stereogenic centers, an overview will be presented to various synthetic studies on clerodane and related natural products, which are of current interest in view of biological activity.

Clerodane diterpenoids from Salvia blepharophylla

Two clerodane diterpenoids, blepharolides A and B, have been isolated from Salvia blepharophylla Brandegee ex Epling. Their structures were determined using a combination of one- and two-dimensional NMR techniques. The relative stereochemistry for blepharolide A was determined by X-ray diffraction. To our knowledge this is the first crystal structure determination of a 5,6-unsaturated octahydro-1 H-cyclopropa[ a]naphthalene derivative.

Clerodendrins from Clerodendron trichotomum and their feeding stimulant activity for the turnip sawfly

Abstract Adults of the turnip sawfly, Athalia rosae ruficornis , are stimulated to feed pharmacophagously on the leaves of Clerodendron trichotomum by bitter neo -clerodane diterpenoids contained in glandular organs on the leaf surface. Four new neo -clerodane analogues, clerodendrins E, F, G and H, were isolated from leaf surface extracts of C. trichotomum . Clerodendrins E, F and G were characterized as analogues of clerodendrin A, in which the acyl moiety at the C-3 β position was replaced by 2-acetoxy-2-methylpropanoyl, 2,3-diacetoxy-2-methylbutanoyl and 2-methylbutanoyl moieties, respectively. Clerodendrin H was shown to be the 7,8-dihydro-derivative of F. Of the seven clerodendrins (A–H) isolated from C. trichotomum , only the 7,8-dihydro analogues (clerodendrins B, D and H) exhibited distinct feeding stimulant activity to adults of the turnip sawfly.

Synthetic studies on clerodane diterpenoids. 4. The total synthesis of (±)-6β-acetoxy-2-oxokolavenool

The first total synthesis of the title compound in racemic form has been accomplished from ketone 4, a readily accessible compound via an intermolecular Diels-Alder approach developed previously for the synthesis of clerodane diterpenoids.

Isolation and characterization of cytotoxic diterpenoid isomers from propolis.

The methanol extract of Brazilian propolis was fractionated by HPLC, based on HuH13 (human hepatocellular carcinoma) cell cytotoxicity assay. Two isomers of diterpenoid with a molecular formula of C20H30O3 (MW: 318.46) were isolated. The structures of these colorless compounds were determined as clerodane diterpenoids (I, 15-oxo-3, 13Z-kolavadien-17-oic acid; II, 15-oxo-3Z, 13E-kolavadien-17-oic acid).

Portulene Acetal, a Novel Minor Constituent of Portulaca grandiflora with Significance for the Biosynthesis of Portulal

A new clerodane diterpenoid (6) with a caged hemiacetal ring has been isolated as a minor constituent from Portulaca grandiflora and its structure elucidated by extensive spectral studies. The compound might be of significance in the biosynthesis and in the chemosystematics of constituents of the genus Portulaca. The structural features of 6 provide important clues for the proposal of a chemically reasonable scheme for the biosynthesis of portulal (1).

Clerodane diterpenoids, long chain esters of coumaric acid and other compounds from Baccharis myrsinites

A new clerodane diterpenoid and two new long chain esters of trans- and cis-coumaric acid, in addition to known triterpenoids and one known clerodane diterpenoid, have been isolated and characterized from Baccharis myrsinites. The structures were determined by spectroscopic techniques.

Clerodane diterpenoids from Cyathocalyx zeylanica

A new clerodane diterpene, 3-hydroxy-cleroda-4(18),13 Z-dien-15-oic acid, been isolated from the stem bark of Cyathocalyx zeylanica along with a known clerodane diterpenoid, 16-acetoxy-cleroda-3,13-dien-15,16-olide. Their structures were determined on the basis of spectral data including 2D NMR spectra and some previous 13C NMR assignments of the latter compound were revised.

A New Clerodane Diterpenoid Isolated from Propolis

Abstract A physiologically active substance has been isolated from Brazilian propolis and charac­terized as a new clerodane diterpenoid, as indicated by human hepatocellular carcinoma HuH 13 cell cytotoxicity assays. This compound inhibited growth of the hepatoma cells at a concentration around 10 μg/ml and arrested the tumor cells at S phase as revealed by flow cytometry. At higher concentrations it exerted lethal damage. The compound showed cyto­toxicity on human lung carcinoma HLC-2, HeLa, KB and rat W3Y cells, whereas human diploid foreskin and primary rabbit kidney cells were less affected.

Structure-Activity Relationship of Clerodane Diterpenoids Acting as Antifeedant Agents

Considering the feeding-deterrent activities exhibited toward Tenebrio monitor (L.) (Coleoptera: Tenebrionidae) of several diterpenes with the clerodane skeleton isolated in our laboratory, a structure-activity relationship study was undertaken. A series of different clerodane diterpenoids was analyzed by performing an exhaustive study of their electronic and conformational behaviors. The results indicate that the antifeedant activity of these clerodane diterpenoids is mediated, at least, through two binding sites. Apparently one important factor contributing to the biological activity is a high conformational flexibility for the torsion angle of the β-furyl group

Cytotoxic constituents of Baccharis gaudichaudiana.

Three new labdane diterpenes, gaudichaudols A-C [1-3], a new clerodane diterpenoid, gaudichaudone [4], and the known clerodane, articulin acetate [5] have been isolated from the aerial parts of Baccharis gaudichaudiana, together with the known compounds, apigenin, hispidulin, spathulenol, and ursolic acid. Through the application of 1D- and 2D nmr spectroscopy, the structures of the new diterpenoids [1-4] were, in turn; elucidated as 15,16,18,19-tetrahydroxylabd-5-ene, 15-O-acetyl-16,18,19-trihydroxylabd-5-ene, 16-O-p-trans-coumaroyl-15,18,19-trihydroxylabd-5-ene, and 2 beta-hydroxy-15,16-epoxycleroda-1(10),15,16-trien-18,19-olide++ +. The isolated compounds were evaluated in P-388 lymphocytic leukemia cells as well as a battery of human cancer cell lines. Among the diterpenoids, gaudichaudol C [3], gaudichaudone [4], and articulin acetate [5] exhibited significant cytotoxic activity against certain cancer cells.

Molecular connectivity and hydrophobicity in the study of antifeedant activity of clerodane diterpenoids

AbstractFeeding deterrent activities of twelve clerodane diterpenoids towards Tenebrio molitor (Coleoptera: Tenebrionidae) larvae have been correlated using molecular connectivity indexes (3χc, 4χc, °ΔX) and hydrophobicity constants (log K′w) obtained by reverse‐phase liquid chromatography (RPLC). The equations obtained suggest that both the degree of branching and the electronic characteristics of the compounds under study have a dominant role in the observed antifeedant activity. The information obtained from the correlations should be useful in designing more potent analogues.

Spruce budworm (Choristoneura fumiferana) antifeedants 3. Structure–activity relationship among some angularly functionalized decalin compounds

Several angularly functionalized decalins, synthethized during the preparation of three keto diacetate decalins, models for clerodane diterpenoids, were tested for antifeedant activity against the spruce budworm, Choristoneura fumiferana. Definite biological activity was observed for some of these compounds. A structure–activity relationship was discussed on the basis of these results.

クレロダンジテルペノイドの合成研究―天然物合成における立体制御の事例

Synthetic studies on the clerodane diterpenoids, a rapidly growing group of natural products, are reviewed from the standpoint of stereocontrols for the construction of a unique four contiguous stereogenic centers on their bicyclic skeleton. Strategies for the clearance of the stereochemical problems are described according to the types of major stereochemical features-namely trans and cis with respects to the ring fusion, and cis and trans disposition of C1-unit at C-8 and C-9 positions. The description involves the methods for enantioselective synthesis. Brief mentions are made on the synthetic methods for the related natural products (sesqui-, di- and sesterditerpenoids) with “clerodane” skeleton or substitution (hence with common problems of the stereocontrol) and on the investigations for the construction of the specific groupings in bioactive clerodane diterpenoids. The preliminary approaches as well as the methods used in the successful total synthesis are introduced in the modern light of stereocontrols.

Reaction of diazomethane with clerocidin. Preparation of new clerodane diterpenoid derivatives

Reaction of 1 with diazomethane in MeOH gave the ketone 2 as well as the diepoxide 4. The alcohol 3, obtained by hydrolysis of 2 was acetylated and oxidized to give 6.

Clerodane and aromatic seco-clerodane diterpenoids from salvia rhyacophua.

The known clerodane diterpenes salviarin 1 and 6β-hydroxy-7,8-dehydrobacchatricunactin 2, were isolated from Salvia rhyacophila together with five new clerodane diterpenoids 3-6 and 12. The structures of diterpenes 3-6 were established on spectral evidence and chemical transformations. Rhyacophiline is an aromatic seco-clerodane diterpenoid whose structure 12 was established by spectral means and X-ray diffraction analysis.

The absolute stereochemistry of some clerodane diterpenoids isolated from Teucrium species

The absolute configurations of four previously isolated clerodane diterpenoids, montanin C, 12-epiteupolin II, teugnaphalodin and teubutilin B, have been established by chemical correlation with some derivatives of 19-acetylgnaphalin, a neo-clerodane whose absolute stereochemistry is known. The above four compounds also belong to the neo-clerodane series.

Biosynthesis of the clerodane furano-diterpene lactone skeleton in Tinospora cordifolia

The isotope ratios in cis-clerodane furanoditerpene lactones labelled from [4 R- 3H 1, 2- 14C]MVA suggested two 1,2-hydrogen shifts and two 1,2-methyl shifts during the formation ofthe ring system of these diterpenes. Chemical degradation of clerodane diterpenoids radiolabelled from [2- 14C]MVA revealed that the gem-methyls of geranylgeranyl pyrophosphate (GGPP) retained their identity during the cyclization.

Tilifodiolide, tetraline-type diterpenoid of clerodanic origin from Salvia tiliaefolia

From the aerial parts of Salvia tiliaefolia Vahl, the known nisovalvipuberulin and two new clerodane diterpenoids, salvifolin and tilifodiolide, were isolated. The structure of salvifolin was deduced from spectral data. The structure of tilifodiolide was established by chemical and spectral means and X-ray diffraction analysis