Bicyclic Diterpenes Research Articles

Antimicrobial Terpenoids from South China Sea Soft Coral Lemnalia sp.

Chemical investigation of the South China Sea soft coral Lemnalia sp. afforded 13 structurally diverse terpenoids, including three new neolemnane sesquiterpene lineolemnenes E–G (1–3); a new aristolane-type sesquiterpenoid, 2-acetoxy-aristolane (4); four new decalin-type bicyclic diterpenes, named biofloranates A−D (5−8); a new serrulatane, named euplexaurene D (9); and a new aromadendrane-type diterpenoid cneorubin K (10), together with three known related compounds (11−13). The structures of the new compounds were elucidated by NMR spectroscopy, the Mosher’s method, and ECD analysis. Compounds 1–13 were tested in a wide panel of biological assays. Lineolemnene J (3) showed weak cytotoxicity against the CCRF-CEM cancer cell line. The isolated new diterpenes, except euplexaurene D (9), demonstrated moderate antimicrobial activity against Bacillus subtilis and Staphylococcus aureus with a MIC of 4−64 μg/mL. Compound 2 exhibited a mild inhibitory effect against influenza A H1N1 virus (IC50 = 5.9 µM).

Terpenoids in the Essential Oil and Concentrated Aromatic Products Obtained from Nicotiana glutinosa L. Leaves.

N. glutinosa L. is a relatively less studied Nicotiana species (Solanaceae), although there are data about its importance as a model plant in viral control studies, as a gene donor in tobacco hybridization and as a source of agents with insecticidal or fungicidal effects. The biological activities of the species were associated mostly with the presence of leaf surface metabolites, in particular diterpenes and sucrose esters. The aim of this study was to identify the chemical composition of the essential oil (EO) and two aromatic extraction products (concrete and resinoid) obtained from N. glutinosa L. leaves. GC-MS analysis identified 26 components in the EO (representing 97.3% of total oil content), which contained mostly diterpene compounds with major components manool (14.2%), sclarene (8.4%) and manoyl oxide (8.1%). The number of compounds identified in the concrete was 37 (95.5% of the total content) and the major component was the diterpene alcohol sclareol (14.2%). In the resinoid, 30 volatile components (representing 95.1% of resinoid content) were identified, with major components nicotine (32.9%), α-tocopherol (8.2%), tridecanoin (6.9%), sclareol (6.9%), and solanone (6.9%). The group of bicyclic diterpenes had the largest share in the diterpene fraction of the products (57.3%, 91.7%, and 86.3%, respectively for the EO, concrete, and resinoid). Considering the abundance of sclareol in the aromatic products, the antimicrobial activity of the pure substance was determined. Sclareol was highly effective against a set of medicinally important yeasts; Candida albicans АТСС 10231, C. glabrata ATCC 90030, C. parapsilosis clinical isolate, and C. tropicalis NBIMCC 23, while being less effective against the studied Gram-positive and Gram-negative bacteria. Data from the study on N. glutinosa aromatic products composition may be of interest to the aroma industries for their possible use in perfumery and cosmetics.

Substrate specificity of the CYC2 enzyme from Kitasatospora griseola: production of sclarene, biformene, and novel bicyclic diterpenes by the enzymatic reactions of labdane- and halimane-type diterpene diphosphates

The enzymatic reaction of copalyl diphosphate (CDP), ent-CDP, syn-CDP, and tuberculosinyl diphosphate with the CYC2 enzyme from Kitasatospora griseola afforded sclarene, biformene, and novel diterpenes having a buta-1,3-diene moiety in the side chain. The substrate specificity of the CYC2 is discussed.

Relationships Among Resin-Producing Detarieae s.l. (Leguminosae) as Inferred by Molecular Data

The tribe Detarieae s.l. (Caesalpinioideae: Leguminosae) contains a large number of genera that produce resins, but which previously had been placed in differrent generic groups. To test the monophyly of the resin-producing Detarieae and to examine phylogenetic relationships among these genera, we analyzed sequences from the chloroplast trnL intron and trnL-F spacer for more than 80 taxa and from the nuclear ribosomal Internal Transcribed Spacers (ITS) for over 50 taxa. The two chloroplast regions were highly congruent, but incongruent with the nuclear ITS data. Incongruence may be the result of hybridization, particularly in the Colophospermum and Hardwickia polyploid lineage. Resin-producing taxa are scattered among two clades, the Prioria and Detarieae s.s. clades, which together are monophyletic, but only with weak support. This group is characterized by the ability to produce bicyclic diterpenes. The phylogenetic relationships as inferred from molecular data resolved the intergeneric affinities but the main clades obtained are different from the groupings proposed by classifications based primarily on morphological characters. Based on these analyses, we propose new generic groupings that correspond to the Prioria s.s., Hardwickia, Hymenaea, Eperua s.s. and Detarium clades.

In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus

Introduction Extracts of Vitex agnus-castus (VAC) are used for the treatment of premenstrual symptoms. The mechanism of action was proposed to be dopaminergic and estrogenic in nature. To isolate these endocrinologically active substances, receptor ligand binding assays and cell cultures were used as in vitro systems to monitor the bioactivity-guided chromatographic separation. Methods Estrogen receptor (ER) and Dopamine D 2-receptor ligand binding assays were performed with human recombinant receptor protein. Both known ERs (ERα and ERβ) were used. Cultures of anterior pituitary cells were prepared from 3 months old female rats. The concentrations of prolactin (PRL) and of cAMP in the supernatants were measured by radio immunoassay (RIA). Starting material for the isolation of single constituents was the aqueous ethanol 70% (v/v) VAC extract BNO 1095. The fractionations were performed with high speed counter current or Sephadex-LH-20 chromatography. Structure elucidation was conducted with GC–MS, LC–MS, 1H NMR and 13C NMR. Results The bio-guided fractionation of BNO 1095 resulted in the isolation of dopaminergic bicyclic diterpenes. The fraction with the highest dopaminergic activity was a mixture of diterpenes of the clerodane type, designated as “BNO-diterpenes”. These newly isolated diterpenes inhibited cAMP formation and PRL-release in rat pituitary cell cultures. The estrogenic compounds in BNO 1095 were identified as the flavonoids penduletin and apigenin. Both substances are specific ligands for the ERβ. Conclusion Using the strategy of bioactivity-guided fractionation we were able to isolate new dopaminergic diterpenes with a high specific activity which contribute significantly to the PRL-lowering activity of VAC. The therapeutical potential of the ERβ specific ligands penduletin and apigenin needs further investigation.

Guyonianin A and B, Two Polyester Diterpenes from Algerian Euphorbia guyoniana

The dichloromethane extract of the aerial parts of Euphorbia guyoniana afforded two new polyester diterpenes, named guyonianin A and B, a rare class of bicyclic diterpenes. Their structures were established by high-field NMR spectroscopic methods, including DEPT, COSY, NOESY, HMQC and HMBC.

Taxadiene Synthase-Catalyzed Cyclization of 6-Fluorogeranylgeranyl Diphosphate to 7-Fluoroverticillenes

The mechanism of the taxadiene synthase-catalyzed cyclization of (E,E,E)-geranylgeranyl diphosphate (GGPP, 7) to taxadiene (5) is proposed to proceed through a verticillen-12-yl carbocation intermediate (8) that undergoes an 11 --> 7 proton transfer leading to formation of the C ring. The substrate analogue 6-fluoroGGPP (17) was synthesized to elucidate the stereochemistry of the putative verticillenyl intermediate. It was expected that the inductive electron-withdrawing effect of the fluoro substituent would prevent the critical proton transfer to the Delta(7) double bond and thereby derail the cyclization at the bicyclic stage. Incubation of the fluoro analogue with recombinant taxadiene synthase yielded a mixture of three major and two minor fluoro diterpenes according to GC/MS analyses. The three major products were identified as the exocyclic, endocyclic, and 4(20)-methylene 7-fluoroverticillenes, i.e., Delta(3,7,12 (18)), Delta(3,7,12), and Delta(4(20),7,11) isomers (22, 23, and 24) on the basis of (1)H NMR analyses and comparisons with the parent bicyclic diterpenes. The H1beta, H11alpha (1S,11R) configurations at the bridgehead positions of 22 were established by means of NOE experiments and CD spectra. The absolute configuration of (+)-verticillol (4) was revised after the anomalous dispersion X-ray analysis of (+)-verticillol p-iodobenzoate. Of particular note, all absolute configurations of verticillane diterpenes in the literature should be reversed. This work affords compelling evidence supporting the H11alpha (11R) stereochemistry of the verticillen-12-yl(+) ion intermediate in the taxadiene synthase-catalyzed reaction and illustrates the capability of vinyl fluoro analogues to intercept complex cyclization cascades.

Side-chain migration reactions and ring B aromatization in labdanes: scope and limitations. Synthesis of isofregenedane type tetrahydronaphthalenic diterpenes

The reaction of bicyclic diterpenes with an allylic oxygenated function or an equivalent functionality on ring B in the presence of I 2/benzene afforded a simple and rapid synthesis of tetrahydronaphthalenic diterpenes of the isofregenedane class.

Cyclization of Bicyclic Diterpenes Promoted by SmI2. Synthesis of Tri- and Tetracyclic Diterpenes

The synthesis of 15-hibaen-14-one (a tetracyclic diterpene) is described from zamoranic acid as starting material in an excellent yield and with total control of the stereochemistry. The key step is a SmI 2 promoted pinacol cyclization.

Euphosalicin, a new diterpene polyester with multidrug resistance reversing activity from Euphorbia salicifolia

A novel diterpene polyester, named euphosalicin (1), the first representative of a new class of bicyclic diterpenes, was isolated from the dichloromethane extract of the whole plant of Euphorbia salicifolia, together with one known (2) and two new jatrophane diterpenes (3, 4). The new carbon skeleton is formally derived from the jatrophane framework by incorporation of a geminal methyl group in the ring system. Compound 1 was found to be more active than verapamil in reversing multidrug resistance in mouse lymphoma cells.

Three New Bicyclic Taxane Diterpenoids from the Needles of Japanese Yew, Taxus cuspidata Sieb. Et Zucc

Three new bicyclic taxane diterpenes were isolated from the needles of the Japanese yew, Taxus cuspidata Sieb. et Zucc. Their structures were established to be 7,9,10,13-tetraacetoxy-5-cinna-moyloxy-4-hydroxy-methyl-8,12,15,15-tetramethyl-bicyclo[9.3.1] pentadeca-3,8,11-trien-2-ol (2,20-dideacetyl taxuspine X), 7,9,10,13,20-pentaacetoxy-5-cinnamoyloxy-8,12,15,15-tetramethyl bicyclo[9.3.1] pentadeca-3,8,11-trien-2-ol (2-deacetyl taxuspine X), and 9,10,13,20-tetraacetoxy-5-cinnamoyloxy-8,12,15,15-tetramethyl-bicyclo[9.3.1] pentadeca-3,8,11-trien-2,7-diol (2,7-dide-acetyl taxuspine X) with the aid of spectroscopic techniques and by comparing with taxuspine X.

I 2 Rearrangement reaction: Synthesis of isofregenedane type diterpenoids

The reaction of bicyclic diterpenes either with an allylic grouping or an equivalent function on ring B afforded a simple and rapid synthesis of tetrahydronaphthalenic diterpenes of the isofregenedane type.

Catalytic hydrogenation in the identification of constituents of an Italian lignite

The terpene content of an Italian lignite was investigated by catalytic hydrogenation of its steam distillate and some reference terpenes. G.c. and g.c.-m.s. analyses of hydrogenated crudes confirmed previous identifications and revealed intermediate structures formed by partial reduction and the presence of bicyclic diterpenes with MW 278. Of the reference terpenes used for comparison with 210 MW sesquiterpene, elemane matched it in R f and mass spectrum. Other identified compounds were some polysubstituted tricyclic diterpenes. Suggestions of an origin in the cupressaceae family could not be confirmed, because of the absence of cuparene and other compounds. The presence of elemane is not easy to explain, but some suggestions are made, and its recent discovery in another fossil of a known but extinct species makes it possible to assign the lignite investigated to a similar species.

Bicyclic diterpenes from two species of brown algae of the dictyotaceae

New diterpenes which possess a decalin skeleton have been isolated from the brown algae, Dictyota dichotoma and Pachydictyon coriaceum and thier structures including absolute stereochemistry have been determined by NMR spectroscopic and chemical means.

Structures of Agelasines, Diterpenes Having a 9-Methyladeninium Chromophore Isolated from the Okinawan Marine Sponge Agelas nakamurai Hoshino

Abstract Novel diterpenes, agelasine-A, -B, -C, -D, -E, and -F were isolated from the Okinawan marine sponge Agelas nakamurai Hoshino and their structures were established to be monocyclic and bicyclic diterpenes having a 9-methyladeninium unit by spectral analyses and chemical transformations.

A new class of macrocyclic diterpenes from [formula omitted][formula omitted] (euphorbiaceae)

Three diterpene acids, representing a new class of bicyclic diterpenes, have been isolated from Bertya dimerostigma F. Muell. (Euphorbiaceae). Spectroscopic and X-ray cryatallographic evidence for their structure is presented. A rationale for their origin via modification of the casbane skeleton is given.

Labdane diterpenes from Cistus symphytifolius

The investigation of the aerial part of Cistus symphytifolius afforded, in addition to sitosterol, trimethoxykaempferol, cativic acid, labdenic acid, labdanolic acid and labdan-8α,15-diol, three new bicyclic diterpenes: cistadienic acid, cistenolic acid and labd-13( E)- ene-8α,15-diol. The structures of these were determined by spectral studies and correlations. CD spectral studies showed that cistenolic acid and salvic acid are enantiomeric compounds, so the stereochemistry of salvic acid (7α-hydroxy-labd-8(17)-ene-15-oic acid) should be changed to 7β-hydroxy-eperu-8(17)-ene-15-oic acid (7β-hydroxy- ent-labd-8(17)-ene-15-oic acid).

A series of novel bicyclic diterpenes from [formula omitted] (brown alga, dictyotaceae)

A series of novel bicyclic diterpenes from [formula omitted] (brown alga, dictyotaceae)

Cationic cyclization of bicyclic diterpenes

Manool and agathadiol cyclize in formic acid to the 13-epimeric pimara-8,15-dienes and 14α-hydroxyhibane derivatives. The mechanistic and biosynthetic implications of these results are discussed in relation to other work involving cations in tetracyclic diterpenes. The nuclear magnetic resonance spectra of relevant tricyclic and tetracyclic diterpenes are documented.

550. Experiments in the synthesis of bicyclic diterpenes

550. Experiments in the synthesis of bicyclic diterpenes