Mannic acid,a new ent-kaurane dimer diterpenoid and other chemical constituents from different parts of Diospyros mannii

A new dimeric ent-kaurane diterpene, mannic acid (1), and 19 known compounds were isolated from the methanol extract of the stems, roots and leaves of Diospyros mannii Hiern (Ebenaceae). Their structures were established by NMR and MS data. This is the first report of asperglaucide from the family Ebenaceae, while mannic acid (1) and xylopic acid (2) are the first ent-kaurane diterpenes isolated from this family. Their chemotaxonomic value is discussed.     

Volatile constituents of four Inula species of Bulgarian origin

In this study the volatile components of four Inula species (Inula germanica L., I. bifrons (L.) L., I. ensifolia L., and I. salicina L.) were analysed by GC-FID/MS. A total of 141 chemical compounds were identified. A distinct volatile chemical profiles with high variation in the type of compounds was observed. Inula germanica was rich in oxygenated monoterpenes (54.7%), with cis-carvyl acetate (20.7%) and 1,8-cineole (14.6%) as main components. Sesquiterpenoids dominated in I. bifrons (60.3%), while the relatively high percentage of fatty acids characterized the other two species I. ensifolia and I. salicina (44.1 and 39.8%, respectively). Principal component analysis (PCA) and cluster analysis (CA) were used to investigate the variations in the volatiles of different Inula species.     

ent-Kaurane diterpenes from the stem bark of Annona vepretorum (Annonaceae) and cytotoxic evaluation

This work describes a novel ent-kaurane diterpene, ent-3β-hydroxy-kaur-16-en-19-al along with five known ent-kaurane diterpenes, ent-3β,19-dihydroxy-kaur-16-eno, ent-3β-hydroxy-kaur-16-eno, ent-3β-acetoxy-kaur-16-eno, ent-3β-hydroxy-kaurenoic acid and kaurenoic acid, as well as caryophyllene oxide, humulene epoxide II, β-sitosterol, stigmasterol and campesterol from the stem bark of Annona vepretorum Mart. (Annonaceae). Cytotoxic activities towards tumor B16-F10, HepG2, K562 and HL60 and non-tumor PBMC cell lines were evaluated for ent-kaurane diterpenes. Among them, ent-3β-hydroxy-kaur-16-en-19-al was the most active compound with higher cytotoxic effect over K562 cell line (IC₅₀ of 2.49 μg/mL) and lower over B16-F10 cell line (IC₅₀ of 21.02 μg/mL).     

New ent-kaurane and ent-pimarane diterpenoids from Siegesbeckia pubescens

Phytochemical investigation of the aerial parts of Siegesbeckia pubescens afforded two new ent-kaurane diterpenoids (1-2), together with sixteen known ent-kaurane and ent-pimarane diterpenoids (3–18). Their structures were elucidated on the basis of extensive spectroscopic methods The absolute configurations of 1–2 and 12 were determined by single-crystal X-ray diffraction analyses. All compounds were evaluated for their cytotoxic activities against two human cancer cell lines A375 and HCT-116.     

Epoxy-isosidol: A new diterpenoid from Sideritis biflora

The new diterpenoid ent-3β-acetoxy-7α,18-dihydroxy-15β,16-epoxykaurane has been isolated from Sideritis biflora. Twelve previously known ent-kaurane derivatives have also been obtained from the same source.     

Two new ent-kaurane diterpenoids from Wedelia trilobata (L.) Hitchc

Two new ent-kaurane diterpenoids, 16α,17,19-trihydroxy-18-nor-ent-kauran-4β-ol (1) and 17-chloro-16β-hydroxy-ent-kauran-19-oic acid (2) were isolated from the whole plant of Wedelia trilobata, together with five known ones (3–7). Their structures were elucidated on the basis of extensive spectroscopic analyses, including NMR and MS techniques. Compound 1 is an 18-nor-ent-kaurane type diterpenoid which is rare in nature, and compound 2 is the first chlorine-containing ent-kaurane diterpenoid so far isolated from plant family of Asteraceae. Known compound 4 was obtained from the genus Wedelia for the first time. Compounds 4–6 selectively showed in vitro antibacterial activity against three assayed Gram-(+) bacteria, especially 5 and 6 which showed the antibacterial activity against Staphylococcus aureus with MIC values (3.125–6.25 μg/mL) comparable to reference compound Kanamycin (MIC 3.125 μg/mL). Compounds 4–6 further displayed significant antibacterial activity against Gram-(−) bacterium Shigella dysenteriae with MIC value 3.125–12.5 μg/mL.     

Diterpenes from Baccharis species

The aerial parts of Baccharis minutiflora afforded in addition to known compounds eight new ent-kaurane derivatives, one being a homo kaurane, while the aerial parts of B. alatemoides gave two pairs of epimeric clerodane derivatives, which, however, had to be modified chemically before they could be separated. The stereochemistry of these diterpenes could not be elucidated with certainty.     

New germacranolides and other constituents from Trichogoniopsis morii

Trichogoniopsis morii afforded, in addition to known compounds, a new toxol derivative, two diterpenes, a labdane and an ent-kaurane derivative, an eudesmanolide and five germacranolides, a furanoheliangolide and four 1-oxo-germacranolides. The structures were elucidated by spectroscopic methods and a few chemical transformations. The chemotaxonomy of the genus Trichogoniopsis is discussed briefly.     

New sesquiterpene lactones from Inula species

An investigation of Inula helenium, I. royleana, I. salicina and I. bifrons afforded in addition to known sesquiterpene lactones 20 new lactones, the eudesmanolides 3, 6 and 8–12, the germacranolides 14–18 and 20–22, the guaianolides 23 and 25, the pseudoguaianolide 26, the xanthanolides 28 and 32 and the cyclopropane analogue 30. Structures and configurations of these new compounds were established by extensive PMR studies and by some chemical transformations. Some of the investigated species contain besides the widely distributed pentaynene 33 several known thymol derivatives together with a new one (40).     

4β,19-Epoxy-norkaurene and other diterpenes from Mikania banisteriae

The aerial parts of Mikania banisterae afforded four new diterpenes, ent-kaur-16-en-18-al, 18-acetoxy-ent-kaurene, 18-hydroxy-16α,17-epoxy-ent-kaurane and 4β-19-epoxy-18-nor-ent-kaurene.     

Two new ent-kaurane diterpenoids from the leaves of Sphagneticola trilobata

Two new ent-kaurane diterpenoids, namely 3α,16α-dihydroxy-ent-kauran-19-oic acid (1) and 3α,9β-dihydroxy-ent-kauran-19-oic acid (2), together with eight known compounds were isolated and identified from the leaves of Sphagneticola trilobata. Their structures were elucidated on the basis of extensive spectroscopic analysis including 1D, 2D NMR and MS techniques. Known compounds 4, 5 and 8−10 were obtained from S. trilobata for the first time. These compounds were tested for their in vitro α-glucosidase inhibitory activity and their tyrosinase inhibitory potential. Compounds 2, 3 and 6 were found to show in vitro α-glucosidase inhibitory activity with IC₅₀ values ranging from 0.398 to 0.476 mM, which were close or more potent than reference compound acarbose (IC₅₀ 0.410 mM). Compounds 2 and 6 were further revealed to show in vitro tyrosinase inhibitory activity (IC₅₀ 29.25 and 40.74 μM) but inferior to that of the positive control kojic acid (IC₅₀ 12.55 μM).     

Cytotoxic ent-kaurane diterpenoids from Isodon sinuolata

Five (1–5) ent-kaurane diterpenoids and 17 other known ones, were isolated from the leaves and stems of Isodon sinuolata. Their structures were determined on the basis of spectroscopic methods including 1D and 2D NMR spectroscopic analysis. All compounds were evaluated for cytotoxicity against a small panel of cell lines. Some compounds exhibited significant cytotoxicity.     

Synthesis and antituberculosis activity of novel unfolded and macrocyclic derivatives of ent-kaurane steviol

New derivatives of steviol 1, the aglycone of the glycosides of Stevia rebaudiana, including a novel class of semisynthetic diterpenoids, namely macrocyclic ent-kauranes were synthesized. These compounds possess antituberculosis activity inhibiting the in vitro growth of Mycobacterium Tuberculosis (H37R_V strain) with MIC 5–20 μg/ml that is close to MIC 1 μg/ml demonstrated by antituberculosis drug isoniazid in control experiment. For the first time it was found that the change of ent-kaurane geometry (as in steviol 1) of tetracyclic diterpenoid skeleton to ent-beyerane one (as in isosteviol 2) influences on antituberculosis activity.     

Chemical composition of Xylopia nitida: Diterpenes and alkaloids

From the roots of Xylopia nitida, were obtained a new natural diterpene, the ent-kaur-16-en-18,19-diol and a new aporphine alkaloid, the 5,6,6a,7-tetrahydro-1-methoxy-(6aS)-4H-benzo[de][1,3]benzodioxolo [5,6-g]quinoline. Some known compounds were also isolated, ent-trachylobane, ent-trachyloban-18,19-diol, ent-trachyloban-18-oic acid, ent-trachyloban-19-oic acid, (−)-xylopine, 1-O-ethyl-β-D-glucopyranose and a mixture of β-sitosterol and stigmasterol. This is the first phytochemical study about X. nitida. In this paper chemotaxonomic significance of these compounds is discussed.     

Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (?)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain.     

New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae)

Fractionation of a MeOH/CH₂Cl₂ (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16α,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7β-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-β-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism.     

Diterpenoids and acetylenic lipids from Aralia racemosa

Phytochemical investigation of Aralia racemosa L. afforded three known diterpenoids and two known acetylenic lipids. The presence of these compounds is consistent with the compound classes reported from other members of genus Aralia. The structures of these compounds were determined by NMR, IR, and LC-MS spectroscopic methods. This is the first report of acanthoic acid from A. racemosa. We present corrected NMR data for (16R)-17-hydroxy-ent-kauran-19-al, which is also reported from A. racemosa for the first time.     

Eudesmanolides and diterpenes from Wedelia trilobata and an ent-kaurenic acid derivative from Aspilia parvifolia

The reinvestigation of the aerial parts of Wedelia trilobata afforded, in addition to known compounds, six new eudesmanolides, two ent-kaurenic acid derivatives as well as a degraded one. A corresponding hydroxy compound was present in Gnaphalium undulatum. From Aspilia parvifolia new ent-kaurenic acid epoxides were isolated. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly.     

Isolation of gibberellin precursors from heavily pigmented tissues

The kauranoid precursors of gibberellins are difficult to isolate from heavily pigmented plant tissues. In this paper, we describe relatively simple and efficient procedures for the purification of these compounds from tissues containing chlorophyll and other high molecular weight pigments. Extracts of shoots from Thlaspi arvense L. were subjected first to size exclusion chromatography using ethyl acetate as the eluting solvent. This procedure resulted in the separation of kauranoids as a class of compounds from chlorophyll. Typically, a 90% reduction in mass of the kauranoid enriched-fraction was observed. This fraction was subjected to reverse phase high performance liquid chromatography and individual fractions analyzed by combined gas chromatography-mass spectrometry. Five kauranoids were identified in shoot extracts of T. arvense: ent-kaur-16-ene, ent-kaur-16-en-19-ol, ent-kaur-16-en-19-oic acid, trachylobanoic acid, and 7β, 13-dihydroxykaurenolide. The metabolic relationships of these compounds to the gibberellins previously identified in this species (JD Metzger, MC Mardaus [1986] Plant Physiol 80: 396-402) are discussed. In addition, the utility of size exclusion chromatography in preparative situations is demonstrated by the purification of ent-kaurenoic acid in milligram quantities from the florets of Helianthus annuus L.