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Neo-clerodane diterpenoids from three species of Teucrium
Abstract
Three species of the genus Teucrium have been investigated. Two of them (T. polium subsp. expansum and T. montbretii subsp. heliotropiifolium) contain known neo-clerodane diterpenoids, and the other one (T. cossonii) provides two new neo-clerodane derivatives (teucossins A and B) together with montanin H, a diterpene recently isolated from another Teucrium species. The structures of the new substances [12xi,19,20-triacetoxy-4alpha,18;15,16-diepoxy-neo-cleroda-13(16),14-dien-6alpha-ol (teucossin A) and 12xi,19-diacetoxy-4alpha,18;15,16-diepoxy-6-oxo-neo-cleroda-13(16),14-diene-(20-O-acetyl) 20S,7alpha-hemiacetal (teucossin B)] were established mainly by spectroscopic means.
... 139 2.2.1.3. Type II subtype Ic with a simple epoxy ring 123,129,139,[141][142][143][144][145][146][147][148] (Table 10 compounds 356-376 found in ESI †). Clerodane diterpenes in this subtype generally have either a 3,4 epoxide (e.g., 357 from Scapania parvitexta, 139 359 from Croton eluteria, 142 364 from Thysanathus spathulistipus 143 ) or a 4,18spiro-oxirane (e.g., 369 from Teucrium oliverianum, 146 375 from T. fruticans 123 ). ...
... 2.2.1.2. Type II subtype Ib with other O-containing rings84,111,[128][129][130][131][132][133][134][135][136][137][138][139][140] (Table 9 -compounds 324-355 found in ESI †). Clerodane diterpenoids with an axial oxyfunction at the C-7 position are rare, but a few examples, such as 326-329, have been reported. ...
Covering: 1990 to 2015The clerodane diterpenoids are a widespread class of secondary metabolites and have been found in several hundreds of plant species from various families and in organisms from other taxonomic groups. These substances have attracted interest in recent years due to their notable biological activities, particularly insect antifeedant properties. In addition, the major active clerodanes of Salvia divinorum can be used as novel opioid receptor probes, allowing greater insight into opioid receptor-mediated phenomena, as well as opening additional areas for chemical investigation. This article provides extensive coverage of naturally occurring clerodane diterpenes discovered from 1990 until 2015, and follows up on the 1992 review by Merritt and Ley in this same journal. The distribution, chemotaxonomic significance, chemical structures, and biological activities of clerodane diterpenes are summarized. In the cases where sufficient information is available, structure activity relationship (SAR) correlations and mode of action of active clerodanes have been presented.
... The CH 3 protons gave a singlet at δ 1.43, which is inappropriate for an acetate ester, with the 13 CH 3 signal at δ 23.9. 2-Bond HMBC linked this CH 3 to the orthoester 13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), of the product 21 of pyrolysis of 19-acetylgnaphalin 27 , and of previously isolated teulepicephin 22 15 . The numbering of the carbon atoms is shown on 1. www.nature.com/scientificreports/ of these signals must have been due to the orthoester carbon (four bonds from H 2 -18) and the other due to acetal carbon C-5 (three bonds from H 2 -18). ...
Teucrium yemense, a medicinal plant commonly grown in Saudi Arabia and Yemen, is traditionally used to treat infections, kidney diseases, rheumatism, and diabetes. Extraction of the dried aerial parts of the plant with methanol, followed by further extraction with butanol and chromatography, gave twenty novel neoclerodanes. Their structures, relative configurations and some conformations were determined by MS and 1-D and 2-D NMR techniques. Most were fairly conventional but one contained an unusual stable orthoester, one had its (C-16)–(C-13)–(C-14)–(C-15) (tetrahydro)furan unit present as a succinic anhydride and one had a rearranged carbon skeleton resulting from ring-contraction to give a central octahydroindene bicyclic core, rather than the usual decalin. Mechanisms are proposed for the biosynthetic formation of the orthoester and for the ring-contraction. Four novel neoclerodanes increased the glucose-triggered release of insulin from isolated murine pancreatic islets by more than the standard drug tolbutamide, showing that they are potential leads for the development of new anti-diabetic drugs.
... 15 Nine other neoclerodanes had been identi ed from this plant by Sattar et al. without evaluation of their biological activity, 9 whereas other neoclerodanes have been isolated from other Teucrium species. 16,17 Neoclerodanes have been also characterised from Scutellaria species 18,19 and Linaria species, 20 while neoclerodanes from Salvia have been identi ed as inhibitors of HSP90 and as κ-opioid receptor agonists. [21][22][23][24] Here, we disclose the isolation and structures of twenty new neoclerodanes from the butanol (BuOH) extract of T. yemense and report that nine examples enhance the insulin-triggered release of insulin from isolated murine pancreatic islets, indicating potential anti-diabetic activity. ...
Teucrium yemense , a medicinal plant commonly grown in Saudi Arabia and Yemen, is traditionally used to treat infections, kidney diseases, rheumatism, and diabetes. Extraction of the dried aerial parts of the plant with methanol, followed by further extraction with butanol and chromatography, gave twenty novel neoclerodanes. Their structures, relative configurations and some conformations were determined by MS and 1-D and 2-D NMR techniques. Most were fairly conventional but one contained an unusual stable orthoester, one had its (C-16)-(C-13)-(C-14)-(C-15) (tetrahydro)furan unit present as a succinic anhydride and one had a rearranged carbon skeleton resulting from ring-contraction to give a central octahydroindene bicyclic core, rather than the usual decalin. Mechanisms are proposed for the biosynthetic formation of the orthoester and for the ring-contraction. Four novel neoclerodanes increased the glucose-triggered release of insulin from isolated murine pancreatic islets by more than the standard drug tolbutamide, showing that they are potential leads for the development of new anti-diabetic drugs.
... Although a large number of these compounds have been isolated from many plants in the last few years, the genus Teucrium is one of the richest sources of neo-clerodane diterpenes: more than 230 diterpenes have been described. Phytochemical investigations of T. polium have been shown that it contains a lot of diterpenes belong to neo-clerodane type [37][38][39][40][41][42][43][44][45] . ...
Teucrium polium L. is a member of the Lamiaceae family and is represented in the Flora of Syria by two variety: Teucrium polium var. angusti folium and Teucrium polium var. mollissimum. Teucrium polium is a wild-growing flowering plant, found abundantly in Syria, and it is used traditional medicine for its diuretic, antipyretic, antispasmodic, tonic, anti-inflammatory, antihypertensive, anorexic, analgesic, antibacterial and antidiabetic effects. Several reports have demonstrated a wide range of beneficial biological and pharmacological activities of the phenylethanoid, phenylpropanoid, and flavonoide components, while the furano neo-clerodane diterpenoids present in germander have been implicated in the in vivo hepatotoxicity of this botanical. Phytochemical studies of this plant have been carried out. Aerial parts of the plant were extracted with petroleum ether at room temperature, and then extract with methanol in Soxhlet, and finally extract with aqueous methanol at room temperature successively. Fractionation of the methanol extract by column chromatography and purification by crystallization yielded three known flvonoides Cirsimartin 2, Cirsiliol 3, and Apigenin 4. The aqueous methanolic extract yielded one new neo-clerodane type diterpenoid, Syrapolin I 1 (3,12- diacetoxy - 4α,18α ; 15,16- diepoxy - 6 – oxo – neo – cleroda - 13 (16), 14- diene -7α, 20β- dihydroxy-19- hemiacetal). The structure of compounds was proposed on the basis of spectroscopic methods IR, MS, and 1-D (1H, 13C and DEPT) and 2-D (COSY, HETCOR, HMBC) NMR experiment, and comparison with closely related compounds.
... 23 The C-4 spiro-oxirane moiety (in 1 and 3) is present in a number of related natural products, including clerodanes isolated from Polyalthia longifolia var. pendula 24 and Teucrium polium, 25 whereas the 5hydroxy furan-2(5H)-one feature (C-13, C-14, C-15, C-16) seen in 1 is less common, being exemplified by salvidin B from Salvia divinorum 15 and rumphioside A from Tinospora rumphii. 26 The lactol functionality in 2 is rare, having only been reported in teupestalin A 27 and four compounds from Teucrium species. ...
Teucrium yemense (Defl), locally known as Reehal Fatima, is a medicinal plant commonly grown in Saudi Arabia and Yemen. Phytochemical investigation of the aerial parts of T. yemense yielded six new neoclerodane diterpenoids, namely fatimanol A–E (1, 2, 3, 5, and 6) and fatimanone (4), and the known teulepicephin (7). As both the Teucrium genus and the related Lamiaceae family have previously been widely reported to possess anthelmintic and antimicrobial activities, the structural and biological characterization of the seven diterpenoids was pursued. The structures of the new compounds were elucidated from their 2D NMR and MS profiles and by comparison to related compounds. The structure of fatimanol D (5) was confirmed by X-ray crystallographic analysis. The new structures contribute to the breadth of knowledge of secondary metabolites in this genus.
... In accordance with the present study, it has been reported that Teucrium polium protects against memory impairments in scopolamine-and diabetes-induced memory impairment models [22,53]. Teucrium polium has been reported to contain diterpenes and flavonoids [54]. The notable activity of Teucrium polium in memory augmentation could be related to its terpenic and flavonoid compounds [55]. ...
Objective. The effects of hydroalcoholic extract of Teucrium polium and metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated. Methods. The rats were divided into: (1) Control, (2) Diabetic, (3) Diabetic-Extract 100 (Dia-Ext 100), (4) Diabetic-Extract 200 (Dia-Ext 200), (5) Diabetic-Extract 400 (Dia-Ext 400), and (6) Diabetic-Metformin (Dia-Met). Groups 3-6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally). Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P < 0.01). In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P < 0.01). Lipid peroxides levels (reported as malondialdehyde, MDA, concentration) in the brain of Diabetic group were higher than Control (P < 0.001). Treatment by all doses of the extract and metformin decreased the MDA concentration (P < 0.01). Conclusions. The results of present study showed that metformin and the hydroalcoholic extract of Teucrium polium prevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.
... Tested extract showed a suffi cient pharmacological activity compared to that of indomethacine (8). Phytochemical investigations led to the isolation of different compounds such as: tridoids and fl avonoids (9), neo-clerodane diterpenoids (10,11), abietane diterpenoids (12) and furanoid diterpenes (13). Moreover, the essential oil from T. polium grown in other countries in the region and of Mediterranean Basin has been also investigated (14)(15)(16)(17)(18)(19). ...
Chemical composition of the essential oil of the aerial parts of Teucrium polium L. grown in Jordan was determined by GC/MS. The oil obtained by hydrodistillation (yield: 0.8 ± 0.04% w/w), was found to contain 39 components, of which 37 were identified. The major components determined were 8-cedren-13-ol (24.8%), β-caryophllene (8.7%), germacrene D (6.8%) and sabinene (5.2%).
... It is widely used in folk medicine; an infusion of the aerial parts is used for abdominal colic and headache, as vermifuge, depurative, antispasmodic, and antidiabetic, and to treat kidney stones (Al-Khalil 1995;Oran and Al-Eisawi 1998;Abu-Irmaileh and Afifi 2000). Different chemical compounds have been isolated and identified from T. polium worldwide, principally: tridoids and flavonoids (Rizk et al. 1986), neo-clerodanediterpenoids (Alcazar et al. 1992;Bedir et al. 1999), abietane diterpenoids (Cuadrado et al. 1992), and furanoidditerpenes (Malakov and Papanov 1983). Utilizing gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS) analysis, several research groups have evaluated the essential oil of T. polium grown in different geographic areas and revealed the presence of several compounds varying in their major constituent(s) and their concentration depending on the geographic origin (Hassan et al. 1979;Rizk et al. 1986;Cakir et al. 1998;Eikani et al. 1999;Aburjai et al. 2006;Kabouche et al. 2007). ...
A protocol for in vitro propagation of the wild germander (Teucrium polium L.) was developed. In vitro plants were developed from ex vitro axillary buds. Then, shoot tips were excised and established on Murashige and Skoog medium. Proliferation of shoots was tested
with different levels of 6-furfurylaminopurin, 6-benzyladenine, or thiadiazuron. The highest proliferation of T. polium was obtained when 6-benzyladenine and 6-furfurylaminopurin were used at 2.0 and 1.6mgl−1, respectively. Thiadiazuron gave the lowest response for shoot proliferation. Rooting was experimented at different levels
of Indol-3-butric acid, Indol-3-acetic acid, or 1-naphthaleneacetic acid. 1-Naphthaleneacetic was the only growth regulator
which promoted root induction. Rooted plants were acclimatized successfully with 75% survival and grown in the greenhouse.
In vitro- and in vivo-grown plants were analyzed for essential oil production. In vitro-grown T. polium on MS medium supplemented with 6-benzyladenine and 1-naphthaleneacetic gave higher oil yield than that grown on hormone-free
Murashige and Skoog medium. In vivo (wild)-grown T. polium produced different oil yield when collected in different months (April and October). β-caryophyllene, used as a marker compound
in the essential oil, was identified and quantified by gas chromatography (GC) analysis. Gas chromatography/mass (GC-MS) spectrometry
analysis was also used to identify other components of in vitro cultures and to compare with in vivo-grown plants.
Keywordsβ-caryophyllene–Essential oil–
In vitro propagation–
Teucrium polium
... On the other hand, Teucrium polium has been reported to contain diterpenes and flavonoids (Malakov et al., 1982;Fernandez et al., 1985;Harborne et al., 1986;Alcazar et al., 1992). Up till now, no AChE inhibitory activity or in vivo antiamnesic result of this species has been reported; however, the notable activity of Teucrium polium in memory augmentation could be again related to its terpenic components. ...
Salvia species and Melissa officinalis are used for their memory-enhancing effects in European folk medicine. Teucrium polium was reported to be used in Anatolia for memory-enhancement in a very old book written by an Ottoman herbalist-physician.
Alzheimer's disease (AD) is a progressive neurological disorder mostly affecting the elder population. Currently, there is no cure for the treatment of severe type of AD. Therefore, in this study, the hydroalcoholic extracts of three traditionally used Lamiaceae species for memory-enhancement; Salvia triloba L., Melissa officinalis L., and Teucrium polium L., were assessed for their in vivo antiamnesic activity along with in vitro anticholinesterase and antioxidant activities.
Scopolamine-induced antiamnesic activity was determined in mice by passive avoidance test, while anticholinesterase effect was measured by spectrophotometric Ellman method at 0.25, 0.50, 1.0, and 2.0 mg ml(-1) and antioxidant activity was assessed by scavenging effect against 2,2-diphenylpicrylhydrazyl (DPPH). Total phenol contents of the extracts were determined by Folin-Ciocalteau method.
Salvia triloba was the most effective in antiamnesic experiment at 100, 200, and 400 mg kg(-1) doses having 22.7, 57.1, and 71.4% of relative effects, respectively. Teucrium polium was also active dose-dependently, whereas Melissa officinalis was completely inactive. In the anticholinesterase assay, the extracts showed similar inhibitions against acetylcholinesterase and Teucrium polium had the highest inhibition (65.8% at 1.0 mg ml(-1)). Concerning the antioxidant effect, all the extracts exerted the highest activity among all having IC50 values between 0.227 and 0.428 mg/ml.
Our data suggest that Teucrium polium among the screened plants deserves to be examined further as a herbal alternative for AD treatment.
Teucrium polium, from Lamiaceae family, is a medicinal plant. Due to overexploitation, low distribution and habitat destruction, this plant, is facing extinction. Plant biotechnology and tissue culture is an alternative method for plant secondary metabolites production. The present study aimed to enhance the production of secondary metabolites and antioxidant capacity of Teucrium polium L. using methyl jasmonate and salicylic acid elicitors. Leaf explants from hydroponically cultured 4-month-old plants were inoculated on Murashige and Skoog medium (MS) containing 2, 4-dichlorofenoxy acetic acid (2, 4-D) in concentrations of 0, 0.5, 1, 1.5 mg/L alone or in combination with benzyl aminopurin (BAP) at, 0.5, 1, 1.5, 2 mg/L concentrations. According to the results, the best callus induction (100%) was achieved at MS medium containing 1.5 and 2 mg/L BAP .Calli obtained from this treatment were subsequently treated with Methyl Jasmonate or Salicylic Acid at 0, 50 and 100 μg/L concentrations. After 40 days, the content of phenolics, flavonoid compounds and total antioxidant capacity were evaluated in a completely randomized design with three replications. Based on biochemical assays, the greatest total phenol content, flavonoids and total antioxidant capacity belong to calli treated with 100 μg/L acid salicylic (SA) and after that to cali treated with 50 μg/L methyl jasmonate(MeJa), while the difference between them was significant. The results of means comparison showed applying 100 μg/L SA on calli in medium with 1.5 mg/L BAP had the greatest effect on total flavonoid content. Therefore, the use of appropriate concentrations of these elicitors can play an effective role in enhancing the medicinal compounds in Teucrium polium.
The genus Teucrium L. has a long-term use in folk medicine, however there are some implications for human health related to the consumption of germander-containing products. Numerous cases of hepatotoxicity have been reported, mostly in Europe, where the plants were used as herbal products for weight loss and still are used in folklore medicine to treat hypercholesteraemia and diabetes. During the last decades several cases of germander toxicity including chronic hepatitis as well as acute cytolytic hepatitis and a case of death have been reported. The most well known toxic Teucrium species are Teucrium chamaedrys, T. polium and T. capitatum, the use of which as herbal medicines and dietary supplements should be strictly controlled. The neo-clerodane diterpenoids occurring in Teucrium species have been the subject of intensive studies, since they have been correlated to the toxic effects of the genus. Studies in mice showed that the hepatotoxicicity of the genus is being induced by this type of diterpenes, which are transformed into their reactive metabolites by P450. Teucrin A and teuchamaedrin A have been subjected to numerous studies in order to reveal the mechanism of action. This chapter aims to summarize the diterpenes isolated from Teucrium spp., as well as the hepatotoxicity of some of them.
Unefficiency of chemical treatments and recent plant protection that is focused on natural products, have pointed the importance of finding natural substances that can help in a control of plant virus diseases. Current knowledge about the antiviral effects of essential oils, although limited, indicates the potential of these secondary metabolites to control or at least reduce the spread of viral infection. Essential oils isolated form Teucrium species showed antiviral activity in tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) infected plants. The aim of this chapter is to present findings dealing with antiphytoviral potential of selected species of genus Teucrium and to improve the knowledge about possible application of essential oils for the prevention of diseases caused by plant viruses. Essential oil of Teucrium arduini applied on the leaves of local host plants, significantly reduced the number of lesions on both TMV and CMV infected plants. Aside from Teucrium arduini, four additional Teucrium species (T. montanum, T. polium, T. chamaedrys and T. flavum) are also source of bioactive molecules with antiphytoviral activity against CMV infection. This promising biological activity of Teucrium species opens new area of research that could help in a control of virus diseases of plants.
The plant Teucrium polium (T.p.) possesses a wide range of pharmacological activities due to the presence, in particular, of different phytochemicals, phenols and flavonoids. We examined the effects of the T.p. extract on impulse activity of hippocampal neurons in a rat model of Alzheimer’s disease. Adult albino rats were divided into three groups (5 animals in each). The control group C obtained intracerebroventricular (i.c.v.) infusions of saline, animals of group Aβ were i.c.v. infused with amyloid β peptide 25–35, Aβ(25–35), and group Aβ+T.p. was treated by both Aβ(25–35) infusions and introductions of the T.p. extract. In group Aβ, a greater proportion of hippocampal neurons with post-tetanic depression after high-frequency stimulation of the entorhinal cortex, lower values of the frequency of background activity generated by the above neurons, and relatively weaker modifications of spike activity (post-tetanic potentiation and depression) were observed. Daily administrations of the T.p. extract partially but considerably reversed the above-mentioned negative shifts in spike activity of hippocampal neurons caused by Aβ(25–35). We suggest that T.p. extract containing important phytochemicals is capable of ameliorating the memory dysfunction caused by Aβ(25–35) via blocking amyloid deposition and a positive influence on the functions of hippocampal neurons.
Furanoditerpenoids are a special group of diterpenoids composing of one or more furan rings, which are rarely found in nature. This review aims to survey the various naturally occurring furanoditerpenoids and their pharmacological activities. A fairly large number of furanoditerpenoids have been reported from the families Euphorbiaceae, Fabaceae and Lamiaceae, and a few ones from the families Asteraceae, Codoniaceae, Dioscoreaceae, Fossombroniaceae, Jamesoniellaceae, Meliaceae, Menispermaceae, Olacaceae, Psathyrellaceae, Sapindaceae and Scapaniaceae. Their distribution correlates strongly with the taxonomic divisions. Most of these plants are widely used in traditional medicines, and furanoditerpenoids have therefore been disclosed with a wide range of bioactivities including anti-cancer, anti-inflammation and anti-microorganism. To structure this review, the furanoditerpenoids were classified into seven types, including clerodane-type (Type I), labdane-type (Type II), cassane-type (Type III), abietane-type (Type IV), spongian-type (Type V), prenylbisabolane-type (Type VI) and miscellaneous type (Type VII). On the basis of 170 references, this review covers the distribution, phytochemistry, synthesis and pharmacological activities of furanoditerpenoids, describing 444 compounds. The information provided in this review might shed light on further research and development of furanoditerpenoids as potential therapeutic agents.
This book series will be kept up to date by concluding every volume with supplementary notes on monographs that have already been published. These notes are not meant to cover all recent references but focus on new and clinically relevant information about the adverse reaction profile of the herbal drug in question.
The chemical constituents of the Labiatae family have been studied mainly for their economic value which is closely related to their high content of essential oils. These consist mostly of volatile mono- and sesquiterpenes. There is much less information on the diterpenoid content of these plants although the latter has been considered (1) potentially more useful for taxonomic purposes.
A new neo-clerodane glucoside, teulamioside, was isolated from the acetone extract of the aerial parts of Teucrium lamiifolium, in addition to the previously known diterpenes montanin E and teuspinin. The structure of teulamioside [(12S)6β-acetoxy- 15, 16; 18,19-diepoxy-neo-cleroda- 13(16),14-dien-20,12-olid-18β-yl- β-d-glucopyranoside] was established by chemical and spectroscopic means.
A new neo-clerodane, scutecyprin, has been isolated from the aerial parts of Scutellaria cypria var. elatior. The structure of scutecyprin was established by comparison of its NMR spectroscopic data with those of closely related compounds.
Some 4α, 18-epoxy-neo-clerodane diterpenoids possessing oxygenated functions at the C-6 and C-19 carbons have been subjected to oxirane-opening reactions with several reagents obtaining chlorohydrins, 4-hydroxy-6,18-ethers, 4-hydroxy-18-O-methyl- and 18-O-acetyl derivatives, allylic C-18 primary alcohols and 4,6,18 and 4,6,19- orthoacetates. These results revealed that the functionality at C-6 and its stereochemistry determine the course of the reaction and affect the retention or inversion of the configuration at the C-4 asymmetric centre. In the light of these reactions, a hypothesis on the biogenetic pathway of some neo-clerodane diterpenoids isolated from Teucrium species is proposed. Moreover, useful criteria for establishing the stereochemistry at C-4 in these derivatives, as well as the unambiguous assignment of the structure of montanin E by an X-ray diffraction analysis and the results achieved in the biological assay as insect antifeedants of several non-natural neo-clerodane derivatives are also reported.
A novel neo-clerodane diterpene, teucrasiolide, was isolated from the aerial parts of Teucrium asiaticum as a mixture of C-15 epimers. Its structure, (15R and 15S, 20R)-15,19-diacetoxy-4α, 18-epoxy-6-oxo-20, 7α-(20-O-acetyl)-hemicetal-neo-cleroda-11E, 13Z-dien-16,15-olide, was established by spectroscopic means.
A novel chlorine-containing neo-clerodane diterpene, teuracemin, (19-acetoxy-18-chloro-15,16-epoxy-4α,7β-dihydroxy-3,6-dioxo-neo-cleroda-13(16),14-dien-20,12S-olide), and three known compounds, teutrifidin, 4α,18-epoxytafricanin A and 20-oxo-teuflavin, were isolated from the aerial parts of Teucrium racemosum.
Some 4α, 18-epoxy- neo -clerodane diterpenoids possessing oxygenated functions at the C-6 and C-19 carbons have been subjected to oxirane-opening reactions with several reagents obtaining chlorohydrins, 4-hydroxy-6,18-ethers, 4-hydroxy-18- O -methyl- and 18- O -acetyl derivatives, allylic C-18 primary alcohols and 4,6,18 and 4,6,19- orthoacetates. These results revealed that the functionality at C-6 and its stereochemistry determine the course of the reaction and affect the retention or inversion of the configuration at the C-4 asymmetric centre. In the light of these reactions, a hypothesis on the biogenetic pathway of some neo -clerodane diterpenoids isolated from Teucrium species is proposed. Moreover, useful criteria for establishing the stereochemistry at C-4 in these derivatives, as well as the unambiguous assignment of the structure of montanin E by an X-ray diffraction analysis and the results achieved in the biological assay as insect antifeedants of several non-natural neo -clerodane derivatives are also reported.
The analysis of the DQF-COSY, TOCSY, and NOESY 1H-NMR spectra, assisted by molecular mechanics calculations, of several neo-clerodane diterpenoids possessing hydroxyl or acetoxyl substituents at the C-12 position, provided an useful method for establishing the C-12 stereochemistry. The preferred rotamer of the C-9 side-chain of these compounds, as well as the identification of their diastereotopic protons at C-11 was also achieved. Thus, the method allowed the assignment of a 12S stereochemistry for teupyrin B (7), teugracilin C (10), montanin H (13), and the diacetyl derivative of teulepicephin (15), all of them previously isolated from Teucrium species, and whose configuration at C-12 remained unknown.
The volatile constituents of Teucrium scordium L. ssp. scordioides, T. polium, and T. montanum, obtained by hydrodistillation, were investigated by GC-FID and GC/MS analyses. A total of 296 constituents were identified, representing 89.8-98.4% of the oil compositions. The oils of T. polium and T. montanum consisted mainly of sesquiterpenes (64.3 and 72.7%, resp.), with germacrene D (4; 31.0%) and δ-cadinene (10; 8.1%) as the main constituents, respectively. In contrast, the monoterpene menthofuran (1; 11.9%) predominated in the oil of T. scordium ssp. scordioides, and this clearly distinguished this species from the other Teucrium taxa investigated up to date. The chemistry of the volatiles of eight Teucrium taxa from Serbia and Montenegro were compared using multivariate statistical analysis, and this provided chemotaxonomically important conclusions.
From the aerial parts of Teucrium montbretii subsp. libanoticum 10 neoclerodane diterpenoids were isolated. Three of them are new [3beta-hydroxyteubutilin A (1), 12-epi-montanin G (2), 20-epi-3,20-di-O-deacetylteupyreinidin (3)], whereas the other seven, namely, 6-ketoteuscordin (4), teuscordinon (5), 6beta-hydroxyteuscordin (6), montanin D (7), 3,20-di-O-deacetylteupyreinidin (8), montanin G (9), and 3-O-deacetylteugracilin A (10), are previously known structures. The structures of 1-3 were determined by spectral and chemical methods.
Due to its liver toxicity, the medicinal use of germander (Teucrium chamaedrys L.) was banned in some countries. Nevertheless, alcoholic extracts are still permitted as flavour ingredients since they are fundamental in providing a bitter aromatic taste. Teucrin A represents the substance of major concern regarding the potential toxicity of germander. Hence, teucrin A represents the best analytical and toxicological marker of alcoholic extracts of T. chamaedrys. A sensitive high-performance liquid chromatography method to detect teucrin A in beverages is reported. Teucrin A was prepared by isolation from the plant extract using column chromatography and crystallization. The identity and purity (99%) were established by melting point, nuclear magnetic resonance and liquid chromatography-mass spectrometry. The high-performance liquid chromatography procedure was validated and its intra- and interday performance was established (relative standard deviation < or = 13% and error < or = 10%). In-house validation was carried out by analysing samples of beverages not containing T. chamaedrys spiked with a range of concentrations of teucrin A. The limit of detection was 0.1 ppm and the limit of quantification was 0.3 ppm. Teucrin A accounted for about 70% of the neo-clerodane diterpenoids found in the total extract of a specimen of T. chamaedrys. The content (+/- standard deviation) in 18 batches of different geographical origin was 2338 +/- 740 ppm, per cent coefficient of variation = 32, minimum-maximum = 999 - 3445 ppm. The mean level of teucrin A in 10 bottles of the same brand was 6.1 +/- 0.8 ppm, per cent coefficient of variation = 12. In 10 different brands found on the Italian market, the content of teucrin A ranged from not detectable to 10 ppm.
A new furanoid diterpene of clerodane type, Montanin-D [1], is isolated from the bitter fraction of the arial parts of Teucrium montanum L., spread in Bulgaria. Its structure is established on the basis of spectral evidance and chemical transformations.
Keywords
Two known furanoid diterpenes Teucrin A (1) and Teucrin E (2) were isolated from the bitter fraction of the aerial parts of Teucrium chamaedrys L. Besides these two compounds, Teuchamaedryn A (3) and B (4) were isolated from the better fraction as well. The structure and the stereochemistry of Teuchamaedryn A, B and Teucrin E were established on the basis of spectral evidence, chemical transformation and correlation.
Two new furanoid diterpenes of clerodane type, 6β-hydroxyteuscordin (1) and 2β, 6β-dihydroxyteuscordin (3) have been isolated from Teucrium scordium var. scordium, Lamiaceae. Their structures and stereochemistry have been determined on the basis of chemical reactions and spectroscopic evidence.
Die Struktur der Diterpenoide (I) wird aufgeklärt.
The structure and stereochemistry of teucrins H1, H2, H3 and H4, four novel diterpenes from Teucrium hyrcanicum have been established by detailed studies of the PMR and 13C NMR spectra, CD results and chemical transformations. Teucrin H4, a minor constituent is shown to possess a unique stereochemistry hitherto not reported for related diterpenoids.
A new clerodane diterpenoid, chamaepitin has been isolated from Ajuga chamaepitys. The previously known clerodanes, 19-acetylgnaphalin, auropolin, teucrin A and teuflin, have been isolated from Teucrium species (T. polium subsp. belion, T. polium subsp. capitatum and T. asiaticum) collected in Majorca. X-ray diffraction analysis on crystals of auropolin has allowed the assignment of configuration at C-20 as S for this compound.
Two new diterpenoids, teucrolivins G and H, have been isolated from the aerial parts of Teucrium oliverianum (Labiatae). The structures of teucrolivin G [6α,19-diacetoxy-4α,18;15,16-diepoxy-3-oxo-neo-cleroda-13(16), 14-dien-12,8β,10β-acetal, 1] and teucrolivin H [19-acetoxy-4α,18;15, 16-diepoxy-6α-hydroxy-3-oxo-neo-cleroda-13(16),14-dien-12,8β,10β-acetal, 2] were established mainly by spectroscopic means, including an X-ray diffraction analysis of the former (1). Compounds 1 and 2 possess an unusual 2,6-dioxabicyclo [2.2.1] heptane structural moiety which, to the best of our knowledge, has now been found for the first time in natural products.
Two new neo-clerodane diterpenoids have been isolated from the aerial parts of Teucrium oxylepis subsp. marianum. Their structures, 4α,18;15,16-diepoxy-6β,12S-dihydroxy-neo-clerado-13(16),14-dien-20,19-olide (teucroxylepin) and 12S-acetoxy-6β,18; 15,16-diepoxy-4α,6α-dihydroxy-neo-cleroda-13(16),14-dien-20,19-olide (12-O-acetylteugnaphalodin), were established by chemical and spectroscopic means. In addition, 10 already known neo-clerodane diterpenoids were also isolated from the same source.
From the aerial parts of Teucrium creticum a new neo-clerodane diterpenoid, teucretol, has been isolated, together with the previously known diterpenoids 6,19- diacetylteumassilin, 19-acetylgnaphalin and teucjaponin B. The structure of teucretol, 6,19-diacetoxy-4α,18;15,16-diepoxy-neo-cleroda-13(16),14-diene-12ξ,20-diol, was established by chemical and spectroscopic means.
This review describes the major advances reported during the last five years on the chemistry of these diterpenoids.
Four newneo-clerodane diterpenoids have been isolated from the aerial parts ofTeucrium gracile. The structures of these compounds, 3β,19-diacetoxy-4α,18;15,16-diepoxy-6β-hydroxy-neo-cleroda-13(16),14-dien-20,12Solide (teugracilin A), 19-acetoxy-4α,18;15,16-diepoxy-3β,6β-dihydroxy-neo-cleroda-13(16),14-dien-20,12S-olide (3-O-deacetylteugracilin A), 19-acetoxy-4α, 18;15,16-diepoxy-3β,6α-dihydroxy-neo-cleroda- 13(16),14-dien-20,12S-olide (teugracilin B) and 12ξ,19-diacetoxy-4α,18;15,16-diepoxy-neo-cleroda-13(16),14-diene-3β,6α-diol (teugracilin C), were established by chemical and spectroscopic means. In addition, the already knownneo-clerodane derivative teumicropodin [3β,19-diacetoxy-4α,18;15,16-diepoxy-6α-hydroxy-neo-cleroda-13(16),14-dien-20,12S-olide] has been isolated from the same source.
From the aerial part of Teucrium fragile a new neo-clerodane diterpenoid, teugin, has been isolated. Its structure, 15,16-epoxy- 2β,6β-dihydroxy-neo-cleroda-3,13(16),14-triene-18,19:20,12S-diolide, was established mainly by spectroscopic means.
The structure of a clerodane-6,7-dione (2), isolated from Teucrium polium L., has been established, and related to that of the corresponding 7-hydroxy-6-ketone picropolin (3). The stereostructures of (2) and (3) are tentatively assigned.
Three new neo-clerodane diterpenoids, teulepicin, 19-acetylteulepicin and teulepicephin, have been isolated, together with the previously known flavone cirsiliol from the aerial parts of Teucrium lepicephalum. The structures of the diterpenoids were established by chemical and spectroscopic means and by correlation with known substances. In addition, 19-acetylteulepicin and the already known neo-clerodane diterpenoid 19-acetylgnaphalin have been isolated from the species T. buxifolium.
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