Dolabellane Diterpenes Research Articles

Dolabellane Diterpenes and Elemane Alkaloids from the Soft Coral Clavularia inflata Collected in the South China Sea.

Five new dolabellane diterpenes, clavularinlides A-E (1-5), and four new racemic elemane alkaloids, clavulacylides A-D (7-10), together with one known compound (6), were isolated from the soft coral Clavularia inflata collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD, and DP4+ probability analyses. Compounds 1-7 showed anti-inflammatory activity in the zebrafish assay.

Semisynthesis of Dolabellane Diterpenes: Oxygenated Analogues with Increased Activity against Zika and Chikungunya Viruses.

Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone (1) and (1R,7R,8R,11S)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (2), isolated from Eunicea genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC50) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound 9 showed an EC50 = 0.92 ± 0.08 μM and SI = 820 against ZIKV.

The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies.

An investigation has been carried out on natural products from dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CLpro) using an in silico approach. Inhibition of the 3CLpro enzyme is a promising target in stopping the replication of the SARS-CoV-2 virus through inhibition of the subsite binding pocket. The redocking process aims to determine the 3CLpro active sites. The redocking requirement showed a good pose with an RMSD value of 1.39 Å. The combination of molecular docking and MD simulation shows the results of DD13 as a candidate which had a good binding affinity (kcal mol−1) to inhibit the 3CLpro enzyme activity. Prediction of binding free energy (kcal mol−1) of DD13 using the Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB/GBSA) approach shows the results ΔGbind(MM-GBSA): −52.33 ± 0.34 and ΔGbind(MM-PBSA): −43.52 ± 0.42. The key residues responsible for the inhibition mechanism are Hie41, Ser46, Met49, Asn142, Cys145, Hie163, Met165, and Gln189. Additionally, pharmacokinetic prediction recommended that DD13 had promising criteria as a drug candidate. The results demonstrated in this study provide theoretical information to obtain a potential inhibitor against the SARS-CoV-2 main protease.

New diterpenes from Nigella damascena seeds and their antiviral activities against herpes simplex virus type-1.

Nigella species are rich source of dolabellane diterpenes. During our study of Nigella species, new dolabellane diterpenes, damasterpenes V-VIII were isolated. The structural determination of new compounds damasterpenes V-VIII is described with consideration of their absolute configurations. The antiviral activities against herpes simplex virus type-1 of the isolated compounds and their derivatives are also evaluated. Damasterpene V (inhibition 35.0%) and 2-phenylacetyl 13-benzoyl damasterpenol (32.0%) showed significant antiviral activity at 10μM.

Dolabellane diterpenes from the Caribbean soft corals Eunicea laciniata and Eunicea asperula and determination of their anti HSV-1 activity

Los dolabellanos son diterpenos con importante actividad antiviral, la mayor parte de los estudios se han realizado con compuestos aislados de algas pardas del género Dictyota. Los corales blandos son también una importante fuente de dolabellanos, pero el potencial antiviral de éstos ha sido muy poco estudiado. Como parte de nuestra búsqueda de compuestos bioactivos a partir de fuentes marinas, se llevó a cabo el estudio químico de los dolabellanos presentes en los octocorales Eunicea laciniata y Eunicea asperula, recolectados en Santa Marta, Caribe colombiano. Los dolabellanos 1-6 fueron aislados del octocoral E. laciniata mientras que en E. asperula se encontraron los compuestos 2, 4 y 5. La elucidación estructural se llevó a cabo mediante experimentos de RMN, espectrometría de masas, rotación óptica y posterior comparación con reportes previos en la literatura. El análisis por CG-EM evidenció que la dolabellatrienona (2) se puede transformar en los compuestos 4 y 5 como producto del almacenamiento prolongado, no obstante, tales compuestos también estuvieron presentes en los extractos de los organismos estudiados. El compuesto 6 inhibió la replicación del VHS-1 (73,7% de inhibición en células infectadas a una concentración de 50 μM) sin efecto citotóxico (CC50 = 959), mostrando una citotoxicidad similar al Aciclovir®, un control positivo, por lo cual se perfila como un candidato para la realización de estudios adicionales sobre el potencial de los dolabellanos como agentes antivirales.

Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity

Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these diterpenoids have strong anti-HIV-1 activity, but there are not data about antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and β-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high antiviral activities, along with their low cytotoxicity, make them promissory antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the antiviral potency of these diterpeneoids.

Dolabelladienols A-C, new diterpenes isolated from Brazilian brown alga Dictyota pfaffii.

The marine brown alga Dictyota pfaffii from Atol das Rocas, in Northeast Brazil is a rich source of dolabellane diterpene, which has the potential to be used in future antiviral drugs by inhibiting reverse transcriptase (RT) of HIV-1. Reexamination of the minor diterpene constituents yielded three new dolabellane diterpenes, (1R*,2E,4R*,7S,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (1), (1R*,2E,4R*,7R*,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (2), (1R*,2E,4R*,8E,10S*,11S,12R*)10,18-diacetoxy-7-hydroxy-2,8-dolabelladiene (3), termed dolabelladienols A–C (1–3) respectively, in addition to the known dolabellane diterpenes (4–6). The elucidation of the compounds 1–3 was assigned by 1D and 2D NMR, MS, optical rotation and molecular modeling, along with the relative configuration of compound 4 and the absolute configuration of 5 by X-ray diffraction. The potent anti-HIV-1 activities displayed by compounds 1 and 2 (IC50 = 2.9 and 4.1 μM), which were more active than even the known dolabelladienetriol 4, and the low cytotoxic activity against MT-2 lymphocyte tumor cells indicated that these compounds are promising anti-HIV-1 agents.

Dictyota dolabellana sp. nov. (Dictyotaceae, Phaeophyceae) based on morphological and chemical data

Abstract Dictyota dolabellana De Paula, Yoneshigue-Valentin et Teixeira is a new species of Dictyotaceae from the South Atlantic Ocean and the first denticulate species in which dolabellane diterpenes have been found. The major compound found in this species is the 4-hydroxy-7,8-epoxy-2-dolabellene. Until now, all populations of thalli containing dolabellane diterpenes had smooth margins and all species with denticulate margins produced prenylated guaiane and xeniane diterpenes. In addition, Dictyota dolabellana differs from other species by the presence of an inconspicuous denticulation irregularly located in the central to upper portions of the frond. Morphological and chemical data and comparison with type materials of other species clearly indicate the presence of a new species.

Cytotoxic Constituents from the Formosan Soft Coral Clavularia inflata var. luzoniana

Three new cytotoxic dolabellane diterpenes, 1-3, three new aromandendrane sesquiterpenoids, 4-6, a new sesquiterpene, 7 (having a new carbon skeleton), and a new cytotoxic xenicane diterpene, 8, were isolated from the methylene chloride solubles of the Formosan soft coral Clavularia inflata var. luzoniana. The structures were elucidated by extensive spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

Enantioselective Total Synthesis of (+)- and (−)-Nigellamine A2

The nigellamine alkaloids are dolabellane diterpenes displaying potent lipid metabolism-promoting activity. Total synthesis of (+)- and (-)-nigellamine A2 has been accomplished. Absolute stereochemistry of synthetic nigellamine A2 was established through an intramolecular asymmetric allylic alkylation using a Pd(phosphinooxazoline) catalyst. Other notable transformations include a radical alkynylation, a diastereoselective Nozaki-Hiyama-Kishi cyclization, and a regio- and stereoselective catalytic epoxidation. On the basis of X-ray crystallographic analysis of an optically active intermediate, we have confirmed the assigned absolute stereochemistry of the natural product. Minor modifications of the synthetic sequence outlined here should provide access to the other nigellamine alkaloids.

A dolabellane diterpene from the brown alga Dictyota pfaffii as chemical defense against herbivores

Laboratory and field experiments assessed the defensive properties of the crude extract and major secondary metabolite found in the Brazilian brown alga Dictyota pfaffii. Natural concentrations of the crude organic extract of D. pfaffii significantly inhibited feeding by the sea urchin Lytechinus variegatus and generalist herbivore fishes in the field. In contrast, the crude extract did not inhibit feeding by the crab Pachygrapsus transversus. Chemical defensive action against the sea urchin and the generalist fishes was due to the diterpenoid 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene found as the major natural product in D. pfaffii. However, this compound did not inhibit feeding by P. transversus as readily as the crude extract. This is the first report showing that Dictyota species produce dolabellane diterpenes as chemical defense against herbivory. In addition, these results widen the action spectrum of secondary metabolites found in species of this brown algal genus. Since dolabellanes constitute the major skeleton type found in Dictyota, we suggest that these diterpenes may play an important ecological function as defenses to the Dictyota species worldwide.

Atranones A–G, from the toxigenic mold Stachybotrys chartarum

Atranones A–G have been isolated from the toxigenic fungus Stachybotrys chartarum. These compounds contain several unusual features including an enol-lactone as part of a 3,7-dioxabicyclo[3.3.0]octane-2-one ring system fused to an 11-membered ring. Two new dolabellane diterpenes, related in structure to the atranones were also isolated, which suggests a diterpenoid origin for the C 24 atranones.

ChemInform Abstract: The Structural Chemistry, Reactivity, and Total Synthesis of Dolabellane Diterpenes

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Three Dolabellanes and a Macrolide from the Sponge Dysidea sp. from Palau

A specimen of Dysidea sp. from Palau contained three new dolabellane diterpenes 1-3 and an unstable 14-membered macrolide, arenolide (4), which showed modest cytotoxicity. From a chemotaxonomic viewpoint, these metabolites are so unusual that we discuss their possible origin.

The Structural Chemistry, Reactivity, and Total Synthesis of Dolabellane Diterpenes

The Structural Chemistry, Reactivity, and Total Synthesis of Dolabellane Diterpenes

3-hydroxy-3-methylglutaryl dolabellane diterpenes from Chrozophora obliqua

From the aerial part of Chrozophora obliqua, 14 novel dolabellane diterpenoids have been isolated, all of them are naturally acylated at the C-16 hydroxyl group with 3-hydroxy-3-methylglutaric acid (HMG). The structures of the isolated compounds were assigned on the basis of deacylation reactions as well as NMR and FAB-MS spectroscopic studies.

Additional dolabellane diterpenes from the Caribbean gorgonian octocoral Eunicea laciniata.

The Caribbean gorgonian octocoral Eunicea laciniata from the coasts of Palomino Island, Puerto Rico, has yielded four known and five new diterpenes based on the dolabellane ring system. The structures of the novel compounds 3-7 were established by interpretation of their spectral data. Some of these new compounds showed weak cytotoxicity against HeLa cells.

An efficient synthesis of the dolabellanes.

Eleven-membered carbocycles have been prepared by the intramolecular condensations of α-sulfonyl carbanions with α,β-unsaturated aldehydes. Desulfonylation provides an efficient stereocontrolled synthesis of allylic alcohols featuring the [9.3.0] cyclotetradecane skeleton which characterizes the dolabellane diterpenes.