A labdane diterpenoid in which the labdane skeleton has double bonds at positions 8(17) and 14 and carries an R-hydroxy group at position 13.
Identification
(3R)-3-methyl-5-[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylenedecahydronaphthalen-1-yl]pent-1-en-3-ol
(+)-manool
(13R)-Labda-8(20),14-dien-13-ol
(13R)-labda-8(27),14-dien-13-ol
(13R)-manool
(5S,9S,10S,13R)-labda-8(17),14-dien-13-ol
labda-8(17),14-dien-13(R)-ol
manool
Species
Europe PubMed Central results
Facile access to optically active labdane-type diterpenes from (+)-manool. Synthesis of (+)-coronarin E, (+)-15,16-epoxy-8(17),13(16),14-labdatriene, and (+)-labda-8(17),13(Z)-diene-15,16-diol.
Author: Villamizar J, Fuentes J, Salazar F, Tropper E, Alonso R.
Abstract: An efficient method for the synthesis of (+)-coronarin E (1), (+)-15,16-epoxy-8(17),13(16),14-labdatriene (2), and (+)-labda-8(17),13(Z)-diene-15,16-diol (3) from (+)-manool is described.
DOI: 10.1021/np030166o
Antiproliferative activity of Greek propolis.
Author: Pratsinis H, Kletsas D, Melliou E, Chinou I.
Abstract: The butanolic extract and the isolated chemical constituents, mainly diterpenes and flavonoids, from Greek propolis have been tested for their cytostatic activities against human malignant and normal cell strains. The extract and the diterpenes were found to be the most active against HT-29 human colon adenocarcinoma cells, without affecting normal human cells. Manool, a diterpene isolated for the first time from Greek propolis, was the most active compound, arresting the cancer cells at the G(2)/M phase of the cell cycle.
Extraction, separation and isolation of volatiles from Vitex agnus-castus L. (Verbenaceae) wild species of Sardinia, Italy, by supercritical CO2.
Author: Marongiu B, Piras A, Porcedda S, Falconieri D, Goncalves MJ, Salgueiro L, Maxia A, Lai R.
Abstract: Isolation of volatile concentrates from leaves, flowers and fruits of Vitex agnus-castus L. have been obtained by supercritical extraction with carbon dioxide. The composition of the volatile concentrates has been analysed by GC/MS. In all plant organs, the extracts are composed chiefly of alpha-pinene, sabinene, 1,8-cineole, alpha-terpinyl acetate, (E)-caryophyllene, (E)-beta-farnesene, bicyclogermacrene, spathulenol and manool. The main difference observed was in the content of sclarene, which was not present in the samples from flowers or fruits. To complete the investigation, a comparison with the hydrodistilled oil has been carried out. The minimal inhibitory concentration (MIC) and the minimal lethal concentration were used to evaluate the antifungal activity of the oils against dermatophyte strains (Trichophyton mentagrophytes, Microsporum canis, T. rubrum, M. gypseum and Epidermophyton floccosum). Antifungal activity of the leaf essential oil was the highest, with MIC values of 0.64 microL mL(-1) for most of the strains.
Chemical composition of endemic Scorzonera sandrasica and studies on the antimicrobial activity against multiresistant bacteria.
Author: Ugur A, Sarac N, Ceylan O, Duru ME, Beyatli Y.
Abstract: The present study describes the antimicrobial activity and chemical composition of Scorzonera sandrasica Hartvig et Strid (Family Asteraceae), endemic to Turkey. The antimicrobial activity of the hexane, chloroform, ethyl acetate, and ethanol extracts of the aerial parts of S. sandrasica was evaluated against microorganisms, including multiresistant bacteria, using a paper disc diffusion method. The chemical composition of the chloroform extract of the plant was determined by gas chromatography and gas chromatography-mass spectrometry. The major compounds of the chloroform extract of the plant were caryophyllene oxide (19.7%), manoyl oxide (16.5%), and manool (11.3%), respectively. The extracts had antibacterial activity; however, no antifungal activity was observed against the two fungi. In particular, the ethanol and chloroform extracts exhibited significant activity against multiresistant strains of Stenotrophomonas maltophilia.
Chemical composition and antimicrobial activity of the essential oils from Cleome spinosa.
Author: McNeil MJ, Porter RB, Williams LA, Rainford L.
Abstract: Five different essential oil extractions of the aerial parts of Cleome spinosa Jacq. were examined. The oils obtained by hydrodistillation of the whole aerial parts, aerial parts without flowers (fruit, leaves and stem), flowers, fruits and leaves have been examined by GC-FID and GC-MS. The chemical profiles of the oils reveal the dominance of oxygenated sesqui- and diterpenes, with the exception of the fruit oil, which contained a high content of fatty acids. The most abundant compounds from the whole aerial parts were (Z)-phytol (31.3%), integerrimine (5.5%) and incensole (4.0%). The major compounds from the aerial portion without flowers were caryophyllene oxide (10.5%), (-)-spathulenol (7.5%) and Z-phytol (6.9%). In the flower oil, the main components were 7-alpha-hydroxy manool (23.8%), incensole (9.2%) and sclareol (8.7%). The chief constituents in the fruit oil were tetradecanoic acid (40.6%), (Z)-phytol (6.58%) and sclareol (4.5%). In the leaf oil, (Z)-phytol (19.5%), 7-alpha-hydroxy manool (6.8%) and caryophyllene oxide (4.36%) were the predominant compounds. Antimicrobial activity of the oil obtained from the whole aerial part was evaluated against nine microbial strains using a filter paper disc-diffusion method. The volatile oil showed moderate action against seven of the eight bacteria strains used, with significant inhibitory activity against Streptococcus pyogenes Group A when compared with the standard antibiotics, ampicillin and gentamicin. The fungus, Candida albicans was less sensitive to the essential oil. The oils showed moderate insecticidal activity against Cylas formicarius elegantalus, but possessed no antioxidant activity as indicated by the DPPH method. This represents the first report on the chemical composition of the essential oils from C. spinosa found in Jamaica and the in vitro antioxidant, insecticidal and antimicrobial potential of the oil from the aerial parts.
Substrate specificity of Rv3378c, an enzyme from Mycobacterium tuberculosis, and the inhibitory activity of the bicyclic diterpenoids against macrophage phagocytosis.
Author: Hoshino T, Nakano C, Ootsuka T, Shinohara Y, Hara T.
Abstract: The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The substrate specificity of the Rv3378c-encoded enzyme was examined. The 3 labdadienyl diphosphates, copalyl diphosphate (CDP) (7), ent-CDP (8), and syn-CDP (9), underwent the conversion reaction, with good yields (67-78%). Copalol (23) and manool (24) were produced from 7, ent-copalol (25) and ent-manool (26) from 8, and syn-copalol (27) and vitexifolin A (28) from 9. The ratio of 23 to 24 was 40 : 27, that of 25:26 was 22 : 50, and that of 27:28 was 16 : 62. Analysis on a GC-MS chromatograph equipped with a chiral column revealed that 24, 26, and 28 consisted of a mixture of 13R- (a) and 13S-stereoisomers (b) in the following ratio: ca. 1 : 1 for 24a to 24b, ca. 1 : 5 for 26a to 26b, and ca. 1 : 19 for 28a to 28b. The structures of these products indicate that the reactions of the 3 CDPs proceeded in the same fashion as that of 2. This is the first report on the enzymatic synthesis of natural diterpenes manool, ent-manool, and vitexifolin A. Both Rv3377c and Rv3378c genes are found in virulent Mycobacterium species, but not in avirulent species. We found that 3 and 4 inhibited the phagocytosis of opsonized zymosan particles by human macrophage-like cells. Interestingly, the inhibitory activity was synergistically increased by the coexistence of 3 and 4b. Other labdane-related diterpenes, 13-16 and 23-28, had little or no inhibitory activity. This synergistic inhibition by 3 and 4 may provide further advantage to the impairment of phagocyte function, which might contribute to pathogenicity of M. tuberculosis.
DOI: 10.1039/c0ob00884b
Isolation and identification of ligands for the goldfish testis androgen receptor in chemical recovery condensates from a Canadian bleached kraft pulp and paper mill.
Author: Scott PD, Milestone CB, Smith DS, MacLatchy DL, Hewitt LM.
Abstract: This study builds on a series of investigations characterizing substances in kraft mill chemical recovery condensates that depress sex steroids in fish. Here, incubations of goldfish testis androgen receptors (AR) with condensate extracts were used to investigate the potential role of androgens in hormone depressions. Condensates contained variable levels of AR ligands, with the highest amounts in nonpolar extracts of filtered solids prior to solid phase extraction (SPE). High pressure liquid chromatography (HPLC) fractionation recovered the majority of activity in one fraction, with ligands detected in three additional fractions. Gas chromatography mass spectrometry analysis of the most active fraction confirmed the two most abundant components as the diterpenes manool and geranyl linalool. Manool exhibited a relative affinity for the AR that was 300 fold less than testosterone and accounted for 26% of total filtered solids activity. Geranyl linalool exhibited no affinity for the AR. Three additional diterpenoid families were tentatively identified as principal components of the three other androgenic HPLC fractions. Compared to condensates, final effluent had 3000 fold less androgenic activity, with <1% attributable to manool. Putative androgens previously associated with mill effluents (androstenedione and androstadienedione) and progesterone were not detected; however, additional condensate diterpenes suspected as androgens were identified in final effluent. This study is the first to confirm nonsteroidal cyclic diterpenes as androgenic at pulp mills. A major in-mill source of these substances was identified, and the role of androgens in mill effluents affecting fish reproduction was reinforced.
DOI: 10.1021/es202732c
Antimicrobial evaluation of diterpenes from Copaifera langsdorffii oleoresin against periodontal anaerobic bacteria.
Author: Souza AB, de Souza MG, Moreira MA, Moreira MR, Furtado NA, Martins CH, Bastos JK, dos Santos RA, Heleno VC, Ambrosio SR, Veneziani RC.
Abstract: The antimicrobial activity of four labdane-type diterpenes isolated from the oleoresin of Copaifera langsdorffii as well as of two commercially available diterpenes (sclareol and manool) was investigated against a representative panel of microorganisms responsible for periodontitis. Among all the evaluated compounds, (-)-copalic acid (CA) was the most active, displaying a very promising MIC value (3.1 µg mL-1; 10.2 µM) against the key pathogen (Porphyromonas gingivalis) involved in this infectious disease. Moreover, CA did not exhibit cytotoxicity when tested in human fibroblasts. Time-kill curve assays performed with CA against P. gingivalis revealed that this compound only inhibited the growth of the inoculums in the first 12 h (bacteriostatic effect). However, its bactericidal effect was clearly noted thereafter (between 12 and 24 h). It was also possible to verify an additive effect when CA and chlorhexidine dihydrochloride (CHD, positive control) were associated at their MBC values. The time curve profile resulting from this combination showed that this association needed only six hours for the bactericidal effect to be noted. In summary, CA has shown to be an important metabolite for the control of periodontal diseases. Moreover, the use of standardized extracts based on copaiba oleoresin with high CA contents can be an important strategy in the development of novel oral care products.
Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture.
Author: Caniard A, Zerbe P, Legrand S, Cohade A, Valot N, Magnard JL, Bohlmann J, Legendre L.
Abstract: <h4>Background</h4>Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species.<h4>Results</h4>Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants.<h4>Conclusions</h4>SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They represent two of the first characterized hydroxylating diTPSs in angiosperms and generate the dihydroxylated labdane sclareol without requirement for additional enzymatic oxidation by activities such as cytochrome P450 monoxygenases. Yeast-based production of sclareol by co-expresssion of SsLPPS and SsSS was efficient enough to warrant the development and use of such technology for the biotechnological production of scareol and other oxygenated diterpenes.
Terpenes From the Root of Salvia hypoleuca Benth.
Author: Saeidnia S, Ghamarinia M, Gohari AR, Shakeri A.
Abstract: <h4>Unlabelled</h4><h4>Background</h4>The genus Salvia, with nearly 900 species, is one of the largest members of Lamiaceae family. In the Flora of Iran, the genus Salvia is represented by 58 species of which 17 species are endemic. Salvia hypoleuca Benth., is one of these species growing wildly in northern and central parts of Iran. Salvia species are well known in folk medicine and widely used for therapeutic purposes. Literature review shows that there is no report on phytochemical investigation of the roots of S. hypoleuca.<h4>Results</h4>The separation and purification process were carried out using various chromatographic methods. Structural elucidation was on the basis of NMR and MS data, in comparison with those reported in the literature. The isolated compounds were identified as sitosteryl oleate (1), β-sitosterol (2), stigmasterol (3), manool (4), 7α-acetoxy royleanone (5), ursolic acid (6), oleanolic acid (7), 3-epicorosolic acid (8), 3-epimaslinic acid (9) and coleonolic acid (10).<h4>Conclusions</h4>In the present study, three sterols, two diterpenes and five triterpenes were isolated from the ethyl acetate extract of the roots of S. hypoleuca. As the chemotaxonomic significance, some of the isolated compounds (1-7, 9) have not been previously reported from the species S. hypoleuca, while the triterpenes 8 and 10 are now documented from Salvia genus for the first time.