Pentacyclic Steroids Research Articles

Taccalonolides: Structure, semi-synthesis, and biological activity.

Microtubules are the fundamental part of the cell cytoskeleton intimately involving in cell proliferation and are superb targets in clinical cancer therapy today. Microtubule stabilizers have become one of the effectively main agents in the last decades for the treatment of diverse cancers. Taccalonolides, the highly oxygenated pentacyclic steroids isolated from the genus of Tacca, are considered a class of novel microtubule-stabilizing agents. Taccalonolides not only possess a similar microtubule-stabilizing activity as the famous drug paclitaxel but also reverse the multi-drug resistance of paclitaxel and epothilone in cellular and animal models. Taccalonolides have captured numerous attention in the field of medicinal chemistry due to their variety of structures, unique mechanism of action, and low toxicity. This review focuses on the structural diversity, semi-synthesis, modification, and pharmacological activities of taccalonolides, providing bright thoughts for the discovery of microtubule-stabilizing drugs.

Synthesis and crystal structures of D-annulated pentacyclic steroids: looking within and beyond AR signalling in prostate cancer

Crystal structures of D-annulated steroids were used for docking studies against the human androgen receptor. The combination of the selected steroid with bicalutamide was found to exhibit significant antiproliferative effects in 22Rv1 cells.

Reactivity of steroidal 1-azadienes toward enamines: an approach to novel chiral penta- and hexacyclic steroids.

The chemical behavior of steroidal N-sulfonyl-1-azadienes toward carbonyl compounds, in the presence of pyrrolidine, is described. With aldehydes, these azadienes participate in hetero-Diels-Alder reactions with the in situ generated enamines. The stereoselectivity results from the approach of the dienophiles from the less hindered α-face of the steroid, with the pyrrolidine moiety endo and retention of the enamine trans geometry. This diastereoselective synthetic methodology led to a new class of chiral pentacyclic steroids. Interestingly, the studied steroidal scaffolds follow a different mechanistic pathway with cyclic ketones. They undergo a diastereoselective annulation reaction, under enamine catalysis, affording chiral hexacyclic steroids.

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells.

The acid-catalyzed cyclization of benzylidenes based on 16-dehydropregnenolone acetate (16-DPA) was studied. It was found that these compounds readily undergo regioselective interrupted Nazarov cyclization with trapping chloride ion and an efficient method of the synthesis of d-annulated pentacyclic steroids based on this reaction was proposed. The structures of the synthesized pentacyclic steroids were determined by NMR and X-ray diffraction. It was found that the reaction affords a single diastereomer, but the latter can crystallize as two conformers depending on the structure. Antiproliferative activity of synthesized compounds was evaluated against two breast cancer cell lines: MCF-7 and MDA-MB-231. All tested compounds showed relatively high antiproliferative activity. The synthetic potential of the protocol developed was illustrated by the gram-scale experiment.

Cycloarta-23-ene-3beta,25-diol a pentacyclic steroid from Euphorbia spinidens, as COX inhibitor with molecular docking, and in vivo study of its analgesic and anti-inflammatory activities in male swiss mice and wistar rats

Background and aimsEuphorbia is a large genus of flowering plants. In Iran, some plants of this family have been used in the treatment of inflammatory disorders and also to relieve back pain. Euphorbia spinidens is a rich source of Cycloarta-23-ene-3beta,25-diol. Cycloartane structures are the starting material for the synthesis of plant steroids, and the aim of this study is to demonstrate COX inhibitory activity, molecular docking and in vivo approach of anti-inflammatory activity of cycloartane compound isolated from Euphorbia spinidens.Material and Methods: Plant material was extracted with acetone-chloroform and submitted to column chromatography for fractionation. Based on preliminary 1H-NMR spectra, cycloartane fraction was selected and purified by repeated recycle HPLC system. The structure and purity of compound were determined by 1H and 13C-NMR, HPTLC, and mass spectra. Inhibitory activities of the tested compounds on COX-1 and COX-2 were evaluated by a colorimetric COX (ovine) inhibitor screening method. Vero cells were used to assess the toxicity against the normal cells, and calculate the selectivity index. COX inhibitory activity results were evaluated and confirmed by molecular docking experiments. In the in vivo approach, analgesic activity was assessed by acetic acid-induced abdominal writhing and formalin tests. Croton oil-induced ear edema in mice and carrageenan-induced rat paw edema in rats were used to evaluate anti-inflammatory activity. Pain tests were carried out on male Swiss mice (25–35 g). Male Wistar rats (160–200 g) were used for the carrageenan test. ResultsCycloart-23-ene-3β,25-diol showedin vitro cyclooxygenase 1 and 2 inhibitory activities with more selectivity for COX-2. Molecular docking by predicting binding energies in COX protein receptors confirmed in vitro COX inhibitory results, and determined the best position for ligand in COX receptors along with its residue interactions in receptor pockets, which must be considered for designing of their inhibitors. In the in vivo studies, cycloartane inhibited significantly acetic acid-induced abdominal contractions and formalin-induced licking behavior at a dose of 200 mg/kg. The same dose reduced croton oil ear edema in mice and carrageenan-induced paw edema in rats. ConclusionTherefore, according to these findings, cycloart-23-ene-3beta,25-diol showed promising analgesic and anti-inflammatory effects with low toxicity against normal cells and can be suggested as a template lead for designing anti-inflammatory compounds with good selectivity index, and potency for COX-2 inhibitory activity.

A New Pentacyclic Ergosteroid from Fungus Aspergillus sp. SCSIO41211 Derived of Mangrove Sediment Sample

Chemical investigation of the fungus Aspergillus sp. SCSIO41211 derived of mangrove sediment sample afforded a ergostane-type pentacyclic steroid, (22 S, 23 R)-12α,14α,23α-trihydroxy-16,22-epoxy-ergosta-4,8-dien-3,11-dione (1), together with seven known compounds, flavacol (2), aspergilliamide (3), ochratoxin A methyl ester (4), ochratoxin A ethyl ester (5), dihydroaspyrone (6), aspilactonol E (7) and aspilactonol F (8). The structures were determined on the basis of NMR and MS analysis. The isolated compounds were tested for their antiviral activity against H3N2 and EV71 viruses, cytotoxic, and antituberculosis effects. Among them, compounds 2 and 5 showed significant cytotoxicity against ten human cancer cell lines. None of the compounds displayed a significant antiviral activity against H3N2 and EV71 viruses nor antimycobacterial activities.

Chemical Composition of Lipids from Peat-Forming Leafy Mosses of Eutrophic Swamps of Western Siberia and Altai

The molecular composition of lipids in three samples of leafy mosses (Aulacomnium palustre, Warnstorfia fluitans, and Calliergon giganteum) has been determined. The revealed acyclic compounds included normal and isoprenoid alkanes, isoprenoid alkenes, normal and isoprenoid ketones, carboxylic acids and their esters, alcohols, and aldehydes. Among cyclic compounds, bi-, tri- and tetracyclic polycycloaromatic hydrocarbons (PAHs), bicyclic and pentacyclic terpenoids, steroids and tocopherols have been observed. The identified organic compounds consisted mainly of carbocyclic acids and n-alkanes with the prevalence of C27 homologues. A. palustre is characterized by a reduced content of isoprenoid compounds, alcohols, and ketones, while the content of unsaturated acids, pentacyclic terpenoids, and aldehydes is rather heightened. A. palustre differs from W. fluitans and C. giganteum in the steroid composition and contains eremophylene, a sesquiterpenoid, which is absent in the mosses of the family Amblystegiaceae. Compared to C. giganteum, W. fluitans has a higher content of lycopadiene, carboxylic acids, n-alkanes, phyt-2-ene, aldehydes, esters, squalene, diploptene, α-tocopherol, and triphenyl phosphates.

A New Neolignan from the Aerial Parts of Prunella vulgaris var. lilacina

Prunella vulgaris is known to contain pentacyclic triterpenoids, flavonoids, phenolic compounds, and steroids. Among the triterpenoids, the oleanane-type, ursane-type, and lupane-type triterpenoids have been known to be predominant. Our phytochemical study led to the isolation of a new neolignan, 9′-O-butyl dehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (1), together with four known compounds, astragalin (2), benzyl-O-β-D-glucopyranoside (3), paeonoside (4), and 4-hydroxybenzoic acid (5). It is noteworthy that all the isolated compounds are reported for the first time from the genus Prunella.

ХИМИЧЕСКИЙ СОСТАВ ЛИПИДОВ ЛИСТОСТЕБЕЛЬНЫХ МХОВ – ТОРФООБРАЗОВАТЕЛЕЙ ЭВТРОФНЫХ БОЛОТ ЗАПАДНОЙ СИБИРИ И АЛТАЯ

The paper describes the molecular composition of lipids in three samples of leafy moss ( Aulacomnium palustre, Warnstorfia fluitans and Calliergon giganteum ). Acyclic compounds such as normal and isoprenoid alkanes, isoprenoid alkenes, carboxylic acids and their esters, alcohols, aldehydes, normal and isoprenoid ketones were identified. Cyclic structures comprised of bi-, tri- and tetracyclic polycycloaromatic hydrocarbons (PAHs), bicyclic and pentacyclic terpenoids, steroids and tocopherols were detected. It was shown that carboxylic acids and n-alkanes with the dominance of C 27 homologue prevail among the organic compounds identified in mosses. It was found that A. palustre is characterized by a reduced content of isoprenoid compounds, alcohols, ketones and high content of unsaturated acids, pentacyclic terpenoids and aldehydes. A. palustre also differs from W. fluitans and C. giganteum in the composition of steroids. The sesquiterpenoid eremophilene was detected in A. palustre, but it is absent in the other mosses. The content of lycopadiene, carboxylic acids, n-alkanes, fit-2-ene, aldehydes, esters, squalene, diploptene, α-tocopherol and triphenyl phosphates is higher in W. fluitans in comparison to C. giganteum .

Antifouling steroids from the South China Sea gorgonian coral Subergorgia suberosa

Two new unusual cholestane derivatives, pentacyclic steroid 16,22-epoxy-20β,23S-dihydroxycholest-1-ene-3-one (1) and 20β,23S-dihydroxycholest-1-ene-3,22-dione (2), along with two new pregnane derivatives, 15β,17α-dihydroxypregna-4,6-diene-3,20-dione (3) and 11α-hydroxypregna-4-ene-3,6,20-trione (4), were isolated from the South China Sea gorgonian coral Subergorgia suberosa. Their structures were established based on the extensive analyses of 2D NMR, IR, and HRMS. Antifouling tests against Balanus amphitrite larvae settlement indicated that 1 and 2 exhibited inhibitory effect with EC50 values of 5.3, and 14.5μg/mL, respectively.

Stereoselective synthesis of pentacyclic steroids functionalized at C-11

We set out to describe an efficient and versatile method for preparing pentacyclic steroids diversely substituted at C-11 from cholic acid, via a stereoselective epoxidation and the epoxide opening as the key steps. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported.

Ring-closing metathesis towards functionalised pentacyclic steroids

A new synthetic pathway towards pentacyclic steroids was described via a ring-closing metathesis reaction as the key step.

ChemInform Abstract: New Synthesis of Pentacyclic Steroids by Stereoselective Epoxide Ring Opening.

AbstractStarting from commercially available cholic acid, the synthesis of a novel class of pentacyclic steroids is described.

New synthesis of pentacyclic steroids by stereoselective epoxide ring opening

A stereoselective synthesis of pentacyclic steroids has been achieved. Starting from commercially available cholic acid 1, followed by asymmetric epoxidation and by stereoselective epoxide ring opening, employing nucleophilic species, the corresponding products were afforded in good yields. The compounds were being evaluated for their biological activity.

Pd(PPh 3) 4/AgOAc-catalyzed coupling of 17-steroidal triflates and alkynes: Highly efficient synthesis of D-ring unsaturated 17-alkynylsteroids

A novel and practical procedure was developed for the preparation of D-ring unsaturated 17-alkynyl steroids by Pd(PPh 3) 4/AgOAc-catalyzed coupling of steroidal 17-triflates and alkynes. Firstly treatment of the steroid-17-ones with PhN(Tf) 2 and KHMDS in dried THF at −78 °C for 2 h gives the corresponding steroidal 17-triflates products in high yields (97–98%), following the coupling of steroidal 17-triflates and various 1-alkynes by Pd(PPh 3) 4/AgOAc-catalyzed in the presence of DIPEA for 24 h to yield the desired D-ring unsaturated 17-alkynyl steroids (86–97%). Moreover, it was found that the coupling reaction catalyzed by Pd[(C 6H 5) 3P] 4/AgOAc system is selective for aryl triflates or vinyl triflates. By optimizing the reaction conditions, the sole C17-coupling products from steroidal bistriflates were obtained in satisfactory yields. Since D-ring unsaturated 17-alkynyl steroids with conjugated double and triplet bond can be subsequently converted into pentacyclic steroids and 17-oxosteroid derivatives at the side chain of D-ring, this general method provides a highly efficient route to these biologically important compounds.

Taccalonolides W – Y, Three New Pentacyclic Steroids from Tacca plantaginea

AbstractThree new pentacyclic steroids, taccalonolides W–Y (2–4, resp.), have been isolated from the whole plants of Tacca plantaginea. Their structures were elucidated on the basis of spectroscopic methods including extensive 1D‐ and 2D‐NMR experiments.

Synthesis of Pentacyclic Steroids via Tandem Stille Coupling and Diels−Alder Reactions

Tandem Stille coupling and Diels−Alder reaction of steroidal iodoalkenyl substrates [17-iodoandrosta-16-ene (2), 17-iodo-3-keto-4-methyl-4-azaandrosta-16-ene (10), and 17-iodo-3-keto-4-azaandrosta-16-ene (11)] were examined in the presence of vinyltributyltin, a dienophile (diethyl maleate, methyl acrylate, dimethyl acetylenedicarboxylate, diethyl fumarate, (−)-di[(1R)-menthyl] fumarate, maleic anhydride), and a palladium catalyst. The yields of novel pentacyclic steroids and the stereochemical outcome of the cycloaddition reaction were investigated under different reaction conditions. In some cases mixtures of isomers were formed, but with dimethyl acetylenedicarboxylate, diethyl fumarate, (−)-di[(1R)-menthyl] fumarate, and maleic anhydride the products could be produced in good yields with high stereoselectivity. The unequivocal assignment of stereoisomers was carried out by various NMR techniques including 1H−1H COSY and NOE experiments.

Facile, high-yielding synthesis of novel pentacyclic steroids

Novel androstane-based skeletons were synthesized in a facile one-pot reaction of 17-iodo-androsta-16-ene, vinyltributylstannane and functionalised olefins. The palladium-catalysed coupling reaction was followed by Diels-Alder reaction resulting in the formation of an unsaturated six-membered E-ring.

Xestobergsterol C, a new pentacyclic steroid from the Okinawan marine sponge Ircinia Sp. and absolute stereochemistry of xestobergsterol A.

A new pentacyclic steroid, xestobergsterol C [1], possessing a cis C/D ring junction, has been isolated together with two known compounds, xestobergsterols A [2] and B [3], from the Okinawan marine sponge Ircinia sp., and the structure determined on the basis of spectral data. Reexamination of the nmr data of xestobergsterols A [2] and B [3] resulted in revision of the configuration at C-23 and of the conformation of ring D in 2 and 3. The absolute stereochemistry of xestobergsterol A [2] was established by the cd exciton chirality method.

Two unique pentacyclic steroids with cis C/D ring junction from Xestospongia bergquistia Fromont, powerful inhibitors of histamine release

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo unique pentacyclic steroids with cis C/D ring junction from Xestospongia bergquistia Fromont, powerful inhibitors of histamine releaseNoboru Shoji, Akemi Umeyama, Kogyoku Shin, Katsuko Takeda, Shigenobu Arihara, Junichi Kobayashi, and Masao TakeiCite this: J. Org. Chem. 1992, 57, 11, 2996–2997Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://doi.org/10.1021/jo00037a009RIGHTS & PERMISSIONSArticle Views204Altmetric-Citations52LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (277 KB) Get e-Alerts Get e-Alerts