Steroidal Ketones Research Articles

Synthesis and biological evaluation of some thiazolidinone derivatives of steroid as antibacterial agents

Steroidal thiazolidinone derivatives were prepared by the multi-step reactions of steroid. It is prepared from steroidal thiosemicarbazones with ethyl bromoacetate in dioxane. Steroidal thiosemicarbazones were prepared by the reaction of thiosemicarbazide with steroidal ketones. The structures of these compounds were elucidated by IR, 1H NMR, Fab mass spectrometries and their purities were confirmed by elemental analyses. The antibacterial activity of these compounds was evaluated by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that steroidal thiazolidinone derivatives are better in inhibiting the growth as compared to steroidal thiosemicarbazone derivatives of both types of the bacteria (Gram-positive and Gram-negative). Compounds 7 and 8 are better antibacterial agents as compared to standard drug Amoxicillin.

Oxidative degradation of model lipids representative for main paper pulp lipophilic extractives by the laccase–mediator system

Different model lipids-alkanes, fatty alcohols, fatty acids, resin acids, free sterols, sterol esters, and triglycerides-were treated with Pycnoporus cinnabarinus laccase in the presence of 1-hydroxybenzotriazole as mediator, and the products were analyzed by gas chromatography. The laccase alone decreased the concentration of some unsaturated lipids. However, the most extensive lipid modification was obtained with the laccase-mediator system. Unsaturated lipids were largely oxidized and the dominant products detected were epoxy and hydroxy fatty acids from fatty acids and free and esterified 7-ketosterols and steroid ketones from sterols and sterol esters. The former compounds suggested unsaturated lipid attack via the corresponding hydroperoxides. The enzymatic reaction on sterol esters largely depended on the nature of the fatty acyl moiety, i.e., oxidation of saturated fatty acid esters started at the sterol moiety, whereas the initial attack of unsaturated fatty acid esters was produced on the fatty acid double bonds. In contrast, saturated lipids were not modified, although some of them decreased when the laccase-mediator reactions were carried out in the presence of unsaturated lipids suggesting participation of lipid peroxidation radicals. These results are discussed in the context of enzymatic control of pitch to explain the removal of lipid mixtures during laccase-mediator treatment of different pulp types.

New data on the effect of steric constraints on the chiral induction in the Orito reaction: Hydrogenation of activated steroid ketones

Hydrogenation of α-ketoesters containing steroid groups at the ester side and at the keto carbonyl function of substrates was investigated the first time on Pt–alumina–cinchona alkaloids chiral catalysts using mild experimental conditions (room temperature, 1 bar hydrogen pressure, modifier concentration 1 mM) in the presence of acetic acid. Catalysts modified by cinchona alkaloids ensured enantioselective hydrogenation with 10–70% ee, depending on the steric structure of the substrate. In the absence of cinchonas racemic hydrogenation takes place, i.e. the chiral centers of the substrates do not participate in chiral induction. Experimental data so far obtained support the assumption that under stereochemical conditions not inhibiting adsorption of the substrate and after optimization of the experimental conditions, the Orito reaction may be rendered suitable for the asymmetric hydrogenation of bulky activated ketones. These results also supply additional evidence for the determinant role of the H-bonded adsorbed intermediate, the 1:1 complex of cinchona alkaloid and substrate in chiral induction under protic conditions.

Synthesis, spectral studies and in vitro antibacterial activity of steroidal thiosemicarbazone and their palladium (Pd (II)) complexes

We investigated the antibacterial activity of some new steroidal thiosemicarbazone and their Pd(II) metal complexes. Metal complexes were prepared from the reaction of steroidal thiosemicarbazone with [Pd(DMSO) 2Cl 2]. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazone to the metal ion, the thiosemicarbazone derivatives were obtained by the thiosemicarbazide with steroidal ketones. All the compounds have been confirmed by spectral data. The antibacterial activity of these compounds was first tested in vitro by the disk diffusion assay against two gram-positive and two gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined. The results showed that steroidal complexes are better inhibit growth as compared to steroidal thiosemicarbazones of both types of the bacteria (gram-positive and gram-negative); compound Ia is better antibacterial agent as compared to amoxicillin.

The conformation of alkyl cyclohexanones and terpenic ketones. Interpretation for the ‘alkylketone effect’ based on the CH/π(C [dbnd]O) hydrogen bond

Ab initio MO calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-311G(d,p) level, to investigate the Gibbs free energy of the conformational isomers of 2-alkyl, 3-alkyl, and 4-alkyl cyclohexanones. The calculation gave results consistent with the general trend experimentally found. The genesis of stabilization of the axial conformers in 2- and 3-alkyl cyclohexanones, as compared to the structurally corresponding cyclohexane derivatives, was sought in the context of the attractive CH/π(C O) hydrogen bond. In support of this hypothesis, short nonbonded distances have been noted between CHs in the alkyl group and the carbonyl carbon in the relevant axial conformers. Calculations were also carried out to study the conformational energies of several terpenic ketones. For isomenthone, more than a half molecular fraction (ca. 55%) has been suggested to be in the isopropyl-axial conformation, while for isocarvomenthone ca. 77% has been suggested to be in the axial-isopropyl conformation; this is consistent with bibliographic experimental data. A crystallographic database search has provided results compatible with this conclusion. We suggest that the relative stability of the axial alkyl substituent, often observed in terpenic and steroidal ketones is rationalized in terms of an attractive molecular force, the CH/π(C O) hydrogen bond.

Synthesis, structure elucidation and antibacterial evaluation of new steroidal -5-en-7-thiazoloquinoxaline derivatives

Some heterocyclic systems namely cholest-5-en-7-thiazolo[4,5- b]quinoxaline-2-yl-hydrazone] were synthesized by the reaction of cholest-5-en-7-one-thiosemicarbazone with 2,3-dichloroquinoxaline at 80 °C in high yield. The thiosemicarbazone derivatives were obtained by the condensation of the thiosemicarbazide with steroidal ketones. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data. The in vitro antibacterial activity was evaluated by disk diffusion method and then the minimum inhibitory concentration (MIC) of compounds was determined against the culture of Escherichia coli. The results were compared with the standard drug chloramphenicol. The results showed that compounds 7 and 8 are better antibacterial agents as compared to chloramphenicol.

The Supertristeroids: Large, Chiral, Molecular Bowls Prepared by Trimerization of Pentacyclic Steroidal Ketones

Robinson annulation of coprostanone (1) at the 2,3- and 3,4-positions gave two pentacyclic enones (7 and 10) that contain A/B-cis-fused ring junctions. Reduction of these enones gave the pentacyclic steroidal ketones 2 alpha,3beta- (8) and 2 alpha,3 alpha-(3'-oxocyclohexano)-5 beta-cholestane (9) and 4 alpha,3beta- (11) and 4 alpha,3 alpha-(3'-oxocyclohexano)-5 beta-cholestane (12). The structures of compounds 8, 9, and 11 were unambiguously established by X-ray analysis. TiCl4-promoted trimerization of compounds 8 and 11 gave the "supertristeroids" 4 and 5, respectively: large (C93) chiral, hydrocarbon clefts with C3-symmetric pockets approximately 12 A in diameter.

LIPID, FATTY ACID, AND STEROL COMPOSITION OF EIGHT SPECIES OF KARENIACEAE (DINOPHYTA): CHEMOTAXONOMY AND PUTATIVE LIPID PHYCOTOXINS1

The lipid class, fatty acid, and sterol composition of eight species of ichthyotoxic marine gymnodinioid dinoflagellate (Karenia, Karlodinium, and Takayama) species was examined. The major lipid class in all species was phospholipid (78%–95%), with low levels of triacylglycerol (TAG; 0%–16%) and free fatty acid (FFA; 1%–11%). The common dinoflagellate polyunsaturated fatty acids (PUFA), octadecapentaenoic acid (OPA 18:5ω3), and docosahexaenoic acid (DHA 22:6ω3), were present in all species in varying amounts (14%–35% and 8%–23%, respectively). The very‐long‐chain PUFA (VLC‐PUFA) 28:7ω6 and 28:8ω3 were present at low levels (<1%), and the ratio of these fatty acids may be a useful chemotaxonomic marker at the species level. The typical dinoflagellate sterol dinosterol was absent from all species tested. A predominance of the 4‐methyl and 4‐desmethyl Δ8(14) sterols in all dinoflagellate species included 23‐methyl‐27‐norergosta‐8(14),22‐dien‐3β‐ol (Karenia papilionacea A. J. Haywood et Steid, 59%–66%); 27‐nor‐(24R)‐4α‐methyl‐5α‐ergosta‐8(14),22‐dien‐3β‐ol, brevesterol, (Takayama tasmanica de Salas, Bolch et Hallegraeff 84%, Takayama helix de Salas, Bolch, Botes et Hallegraeff 71%, Karenia brevis (C. C. Davis) G. Hansen et Moestrup 45%, Karlodinium KDSB01 40%, Karenia mikimotoi (Miyake et Kominami ex Oda) G. Hansen et Moestrup 38%); and (24R)‐4α‐methyl‐5α‐ergosta‐8(14),22‐dien‐3β‐ol, gymnodinosterol, (K. mikimotoi 48%, Karenia umbella de Salas, Bolch et Hallegraeff 59%, Karlodinium veneficum (D. L. Ballant.) J. Larsen 71%–83%). In Takayama species, five steroid ketones were identified, including for the first time the 3‐keto form of brevesterol and gymnodinosterol. These results indicate a biochemical link between sterol and steroid ketone biosynthesis, suggesting that selected dinoflagellates can make a significant contribution to ketones in marine sediments. The presence of steroid ketones, specific sterols, and fatty acids, and the ratio of VLC‐PUFA may prove to be a useful chemotaxonomic tool for distinguishing between morphologically similar species. The relative levels of the PUFA, OPA, and DHA, coupled with the potential inhibitory action of Δ8(14) sterols, may provide an insight into the ichthyotoxicity of these bloom‐forming dinoflagellates.

Ketosteroids from the far-east marine prosobranch mollusk Onchidiopsis variegata

The composition of the ketosteroid fraction from the Far-East marine prosobranch mollusk Onchidiopsis variegata was determined. The structure of a new steroidal ketone cholesta-4,24-dien-3-one (1e) was established by NMR, IR, UV, and mass spectroscopy. It was proposed that O. variegata feeds on ascidians of the genus Styela.

Synthesis, characterization and in vitro antibacterial activity of new steroidal thiazolo quinoxalines

Herein, we report the synthesis of different steroidal thiazolo quinoxaline derivatives as antibacterial agents against Escherichia coli. Steroidal ketone thiosemicarbazones ( 4–6) were obtained from corresponding ketones ( 1–3) by refluxing with thiosemicarbazide. The thiosemicarbazones on reaction with 2,3-dichloroquinoxalines at 80 °C gives 3β-acetoxy-5α-cholestan-6-[thiazolo(4,5- b)quinoxaline-2-yl-hydrazone] ( 7), 3β-chloro-cholestan-6-[thiazolo(4,5- b)quinoxaline-2-yl-hydrazone] ( 8), and 5α-cholestan-6-[thiazolo(4,5- b)quinoxaline-2-yl-hydrazone] ( 9). The structures of the compounds were evident by elemental, IR, 1H NMR and FAB mass spectral analyses. The antibacterial activities of these compounds were evaluated by disk diffusion method against the culture of E. coli and the results were compared with the standard drug amoxicillin. The results reveal that the compounds are better antibacterial agents as compared to amoxicillin. Among all the three compounds ( 7–9), compound 8 showed better zone of inhibition.

Ketones in the catalytic three-component “one-pot” Kabachnik-Fields synthesis of α-amino phosphonates

Reactions of carbocyclic, heterocyclic, and steroidal ketones with benzylamine and diethyl phosphite in a catalytic three-component “one-pot” synthesis of α-amino phosphonates were studied. The activities of mono-and binuclear complexes of tetra(tert-butyl)phthalocyanines as catalysts for this process were compared.

Chemical Composition of Abaca (Musa textilis) Leaf Fibers Used for Manufacturing of High Quality Paper Pulps

The chemical composition of leaf fibers of abaca (Musa textilis), which are commonly used for high-quality paper pulp production, was thoroughly studied. The results revealed that the lignin content was 13.2% of the total fiber. The analysis of abaca fibers by pyrolysis coupled to gas chromatography-mass spectrometry (Py-GC/MS) released predominantly compounds arising from lignin and p-hydroxycinnamic acids, with high amounts of 4-vinylphenol. The latter compound was demonstrated to arise from p-coumaric acid by pyrolysis of abaca fibers in the presence of tetramethylammonium hydroxide, which released high amounts of p-coumaric acid (as the methyl derivative). Products from p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) propanoid units, with a predominance of the latter (H:G:S molar ratio of 1.5:1:4.9), were also released after Py-GC/MS of abaca fibers. Sinapyl and coniferyl acetates, which are thought to be lignin monomer precursors, were also found in abaca. The extractives content of the abaca fiber (0.4%) was low, and the most predominant compounds were free sterols (24% of total extract) and fatty acids (24% of total extract). Additionally, significant amounts of steroid ketones (10%), triglycerides (6%), omega-hydroxyfatty acids (6%), monoglycerides (4%), fatty alcohols (4%), and a series of p-hydroxycinnamyl (p-coumaric and ferulic acids) esterified with long chain alcohols and omega-hydroxyfatty acids were also found, together with minor amounts of steroid hydrocarbons, diglycerides, alpha-hydroxyfatty acids, sterol esters, and sterol glycosides.

Reduction of various ketones by red algae

The reduction of acetophenone derivatives, (+)- and (−)-camphorquinones and steroidal ketones using red algae ( Cyanidioschyzon merolae 10D and Cyanidium caldarium) was investigated. It was found that fluoro, chloro and bromo acetophenone derivatives 1a– i were reduced with good enantioselectivity. On the contrary, reduction of methyl and methoxy acetophenone 1j– o showed low enantioselectivity. The reduction followed Prelog’s rule, giving the ( S)-alcohols in all cases. Moreover, (+)- camphorquinone 5a was reduced to give (−)-3 S- exo-hydroxycamphor 5d as the major product with high stereoselectivity in high yield. In addition, it was found that reduction of 5α-androstane-3,17-dione 8a gave the 3α-OH isomer (3α-OH/3β-OH = 76/24) with high stereoselectivity. Overall it was found that C. merolae and C. caldarium were able to reduce various substrates.

Reduction of Steroidal Ketones with Amine—Boranes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Trofimov Reaction with Oximes Derived from Ketosteroids: Steroid—Pyrrole Structures.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reduction of steroidal ketones with amine—boranes

Complexes of secondary amines with borane, R2NH·BH3, surpass sodium borohydride as reducing agents for saturated and unsaturated steroidal 3-, 12-, 17-, and 20-ketones as regards chemo- and regioselectivity and mildness of the reaction conditions. In the case of 12-ketones, stereoselectivity is also improved.

Sterols of the heterotrophic dinoflagellate, pfiesteria piscicida (dinophyceae): is there a lipid biomarker?1

Within U.S. waters, blooms of the dinoflagellate, Pfiesteria piscicida, have been recorded on an almost regular basis in the Chesapeake Bay and surrounding mid‐Atlantic regions for the last two decades. Despite the apparent significance of such blooms to the environment and human health and the attendant economic consequences, little work has addressed the physiology and biochemistry, particularly that of sterol composition, of P. piscicida. GC‐MS characterization of trimethylsilyl ether derivatives of sterols from free sterol and sterol ester fractions was performed in an effort to determine whether P. piscicida produces unique sterols that may serve as potential biomarkers. This characterization revealed that like most dinoflagellates, the majority of sterols was present as free sterols. Furthermore, the profile of free sterols was found to resemble those of photosynthetic dinoflagellates, with the dominant compound being the previously reported dinoflagellate sterol, dinosterol. A number of other 4α‐methyl‐substituted sterols and steroidal ketones common to other dinoflagellates were also identified. No strong candidate(s) for a unique sterol biomarker was present.

Steroidal Polyols from Far‐Eastern Starfishes Henricia sanguinolenta and H. leviuscula leviuscula.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Investigation on the Regioselectivities of Intramolecular Oxidation of Unactivated C—H Bonds by Dioxiranes Generated in situ.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Trofimov Reaction with Oximes Derived from Ketosteroids: Steroid-Pyrrole Structures

Steroidal ketone oximes, namely pregnenolone oxime, Δ5-cholesten-3-one oxime, and progesterone dioxime react with acetylene in superbasic systems (Trofimov reaction) to afford steroid-pyrrole assemblies. The process is accompanied by prototropic migration of double bonds in the steroid fragment and vinylation of hydroxy groups in sterols with acetylene. The O-vinyl group can readily be removed by methanolysis.