Reduction Of Double Bond Research Articles

A concise synthesis of (R)-Bgugaine, a pyrrolidine alkaloid from arisarum vulgare

A new short method for the preparation of (R)-Bgugaine (1) has been described using Wittig condensation of a non-stabilised ylide with N-carboethoxy prolinal followed by reduction of double bond and conversion of N-carboethoxy group to N-methyl.

Synthesis of tritium‐ and deuterium‐labeled budesonide

AbstractTritium‐labeled budesonide was prepared by the selective reduction of a double bond in the butenylenedioxy side chain using carrier‐free tritium and palladium on carbon as a catalyst in absolute ethanol. Although the reduction gave a mixture of the desired product and the expected byproducts resulting from over reduction of the other double bonds in ring A, the desired tritium‐labeled budesonide was easily isolated by reverse phase HPLC and with specific activity of 54 Ci/mmol. [D8]‐budesonide was prepared from 16α‐hydroxyprednisolone and D8‐butyraldehyde in 1,4‐dioxane in the presence of perchloric acid. The isotopic enrichment was found to be more than 99 atom% D. Copyright © 2008 John Wiley & Sons, Ltd.

Modifications of Aliphatic Side Chain of 20(S)-Ginsenoside Rg3 Cause an Enhancement or Loss of Brain Na+ Channel Current Inhibitions

A line of evidence has shown that ginsenoside Rg3 (Rg3) could be one of bioactive ligands in brain Na+ channel regulations. Rg3 exists as stereoisomer of 20(R)- or 20(S)-form. Rg3 consists of three different parts; steroid- like backbone structure, carbohydrate portion, and aliphatic side chain [-CH2CH2CH=C(CH3)2], which is coupled to the carbon-20 of backbone structure. In the previous report, we demonstrated that 20(S)- but not 20(R)-Rg3 and carbohydrate portion of Rg3 play important roles in rat brain NaV1.2 channel regulations. However, little is known about the role of aliphatic side chain coupled to the carbon-20 in brain Na+ channel regulations. In the present study, we prepared Rg3 derivatives by modifying the aliphatic side chain of Rg3, remaining with backbone structure and carbohydrate portion intact, and examined the effects of Rg3 derivatives on Na+ channel activity. We found that reduction of double bond in aliphatic side chain of Rg3 exhibited agonistic actions in Na+ channel current inhibitions by shifting concentration-response curve to leftward by three-fold, whereas deletion, hydroxylation, or oxygenation of aliphatic side chain caused an attenuation or loss of Na+ channel current inhibitions. These results provide evidences that the aliphatic side chain of Rg3 is also involved in Na+ channel regulations and further show a possibility that the aliphatic side chain of Rg3 could be the target of chemical modifications for abolishment or potentiation of Rg3 actions in Na+ channel regulations.

In Vitro Metabolism of Isoliquiritigenin by Human Liver Microsomes

Isoliquiritigenin (2',4',4-trihydroxychalcone), a chalcone found in licorice root and other plants, has shown potent antitumor, antioxidant, and phytoestrogenic activity in vitro. In preparation for in vivo studies, the metabolism of isoliquiritigenin by human liver microsomes was investigated, and seven phase 1 metabolites were identified. In addition to aromatic hydroxylation that occurred on the A or B ring to form 2',4,4',5'-tetrahydroxychalcone or butein, respectively, reduction of the carbon-carbon double bond of an alpha,beta-unsaturated ketone and cyclization occurred to form 2',4,4'-trihydroxydihydrochalcone and (Z/E)-6,4'-dihydroxyaurone. All metabolites were characterized and identified by using liquid chromatography-tandem mass spectrometry with comparison to authenticated compounds. Finally, monoclonal antibody inhibitors of specific human cytochrome P450 (P450) enzymes and recombinant human P450 enzymes were used to identify the enzymes responsible for the formation of the major mono-oxygenated metabolites, and P450 2C19 was found to be a significant enzyme in the formation of butein from isoliquiritigenin, which also has anticancer activity. Cytochromes P450, reactive oxygen species, and peroxidases can all contribute to the formation of (Z/E)-6,4'-dihydroxyaurone in human liver microsomes.

Degradation of alkenones by aerobic heterotrophic bacteria: Selective or not?

Four bacterial communities were isolated from Emiliania huxleyi strain TWP1 cultures before and after the algal cells had been treated with different antibiotics. Incubation of E. huxleyi with these bacterial communities resulted in dramatically different extents of alkenone degradation, ranging from effectively none to extensive. Selective degradation of the more unsaturated alkenones was observed in experiments using the total bacterial community and one of the communities isolated from antibiotic-treated algal cells. The observed increases in U 37 K ′ are equivalent to a +2 °C and +3.3 °C change in the inferred temperature. Our results clearly show that intense aerobic microbial degradative processes have the potential to introduce a significant ‘warm’ bias in palaeotemperature reconstruction and could explain apparent anomalies in palaeotemperatures inferred from alkenone distributions in strongly oxidizing sedimentary environments. The results show that aerobic bacteria capable of selectively degrading alkenones are not limited to particular environments such as microbial mats and can be actually associated with living E. huxleyi cells. The detection of epoxyketones in some cultures indicates that metabolic pathways involving attack at the terminal groups of the molecule are essentially non-selective, while those acting on alkenone double bonds are selective. The epoxyketones resulting from bacterial epoxidation of alkenone double bonds could be useful indicators of aerobic bacterial alteration of the alkenone unsaturation ratio in situ. The production of alkenols during incubation with one of the bacterial communities demonstrated for the first time that bacterial reduction of alkenones can be a potential source of these compounds in the environment. The intriguing production of small amounts of monounsaturated alkenones by one of the bacterial communities also raises the possibility of a bacterial reduction of alkenone double bonds.

Overexpression of ZmOPR1 in Arabidopsis enhanced the tolerance to osmotic and salt stress during seed germination

12-Oxo-phytodienoic acid reductases (OPRs) are enzymes that catalyze the reduction of double bonds in α,β-unsaturated aldehydes and ketones. In this research, we isolated a full length OPR1 cDNA from Zea mays, which was designated as ZmOPR1. Transcriptional profiling indicated that ZmOPR1 was induced by osmotic stress as well as high salt in the roots of maize seedlings, while the induction of the ZmOPR1 was hardly observed in the leaves. In addition, expression analysis results showed that ZmOPR1 had the highest expression during early seed germination. ABA stress also resulted in a massive accumulation of ZmOPR1 transcripts in both the leaves and roots of maize seedlings. To further explore its biological function, we generated transgenic Arabidopsis plants expressing ZmOPR1 under regulation of the cauliflower mosaic virus CaMV 35S promoter. The transgenic plants exhibited an enhanced level of resistance to osmotic and salt stress during seed germination. Further, RNA gel blot analysis revealed that the expression of ZmOPR1 altered the transcription of some abiotic stress-related genes, including RD22, RD29B and ABF2.

Synthesis of nitrogen-containing spirocyclic scaffolds via aminoallylation/RCM sequence

A concise route to nitrogen-containing spirocyclic scaffolds was developed. It is based on the allylation of imines derived from cyclic ketones. The resulting homoallylamines were subsequently alkylated with bromomethylmethacrylate resulting in propenyl-butenyl substituted amine derivatives. Basic amines such as 4 or 10 were cyclized with the Grubbs 2nd generation catalyst in the presence of pTsOH. Carbamate derivatives could be converted to tetrahydropiperidine derivatives with the same catalyst. It could be shown that the acrylate functionality can be degraded to the ketone using the classical sequence consisting of Curtius rearrangement of the derived acrylic acid followed by hydrolysis of the vinyl isocyanate. Other modifications include reduction of the acrylate double bond, saponification of the ester group, and amide formation.

Synthesis of Tetrahydrodiazepinopurines by Ring-Closing Metathesis

The tetrahydrodiazepinopurine ring system B (n = 1), the core of asmarine, isolated from the marine sponge Raspailia sp., was synthesized via ring-closing metathesis (RCM) for the first time. Similarly, the diazocino analogue B (n = 2) was obtained. For the former, 6-chloropurine was treated with allyl amine or allyl alcohol in the presence of pyridine to give intermediate A. The formation of C-9-alkylated product A rather than the C-7 product is significant because normally in such reactions a mixture of N-7 and N-9 alkylation derivatives is obtained. Interestingly, the RCM was achieved only in the case of the X = N-Boc derivative giving excellent yield (95%) of product, while others, with X = H, Me, failed even at elevated temperatures. Removal of N-Boc protection before double bond reduction failed for the B (n = 1) product, a reaction which was successful for B with n = 2.

Gold Catalysts Open a New General Chemoselective Route to Synthesize Oximes by Hydrogenation of α,β-Unsaturated Nitrocompounds with H2

The unprecedented chemoselective reduction of α,β-unsaturated nitroalkenes to oximes using hydrogen has been achieved with gold nanoparticles supported on TiO2. In contrast to the excellent catalytic performance of gold, related palladium and platinum catalysts are unselective, leading to the reduction of CC double bond as well as the reduction of the NO2 to NH2. The selectivity of Au/TiO2 for the formation of oximes opens the way for the general use of the Henry reaction in organic synthesis.

Transformation of steroids by actinobacteria: A review

Development of pharmaceutical industry is currently aimed at introducing biotechnological processes on a large-scale and thereby replacing multiple-stage chemical syntheses. Actinobacteria are efficient biocatalysts of many processes involving steroid bioconversion, which hold considerable importance for the synthesis of hormonal drugs. The potential to catalyze the conversion of a broad spectrum of steroid substrates makes it possible to expect efficient utilization of these microorganisms in development of new technologies of manufacturing steroid pharmaceutical substances. The review is a first attempt to systematize data on the potential of actinobacteria to catalyze diverse reactions of steroid transformation (such as hydroxylation, introduction and reduction of double bonds, oxidation of steroid alcohols, reduction of ketones, side chain de-esterification and degradation, etc.), with emphasis on processes of practical biotechnological importance and progress in steroid bioconversion over the last ten years.

Rh-Catalyzed Hydrogenation of Olefins with Zn Metal and Water

A very simple and highly practical method for the reduction of double bonds, including α,β-unsaturated ketones, is described. Zinc and water are used as reducing agents. The process does not require special precautions needed for the handling of flammable hydrogen gas or complex hydrides or the use of a pressure apparatus. In the case of α,β-enones, including cyclic systems, the reaction is completely selective for the C=C reduction, so that it complements well the Luche method for the reduction of enones to allylic alcohols. This method can be conveniently used for the preparation of deuterium-labeled compounds, using cheap D2O as the deuterium source.

Field-emission characteristics of diamond-like amorphous carbon films deposited by mixed gas (N 2 or H 2) controlled i-C 4H 10 supermagnetron plasma

Diamond-like amorphous carbon (DAC) films were deposited for field-emission application using supermagnetron plasma by mixing N 2 or H 2 in i-C 4H 10 gas at the upper and lower electrode rf powers (UPRF/LORF) of 800 W/100–800 W. At an 800 W/800 W, the N 2 (0–80%) gas-mixed DAC films showed an emission threshold electric field ( E TH) of 19 V/μm. At the 800 W/100 W, the H 2 (20%) gas-mixed DAC film showed low E TH's of 13 V/μm, respectively. The moderate reduction of CC and CN double bonds by the decrease of LORF from 800 W to 100 W was found to be effective to lower E TH.

Regiospecific solvent-free transfer hydrogenation of α,β-unsaturated carbonyl compounds catalyzed by a cationic ruthenium(II) compound

[(PPh 3) 2Ru(CH 3CN) 3Cl][BPh 4] has been found to catalyze the selective reduction of double bonds in α,β-unsaturated ketones with high conversions when formic acid is the hydrogen donor.

The metabolomics of (±)-arecoline 1-oxide in the mouse and its formation by human flavin-containing monooxygenases

The alkaloid arecoline is a main constituent of areca nuts that are chewed by approximately 600 million persons worldwide. A principal metabolite of arecoline is arecoline 1-oxide whose metabolism has been poorly studied. To redress this, synthetic (±)-arecoline 1-oxide was administered to mice (20 mg/kg p.o.) and a metabolomic study performed on 0–12 h urine using ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry (UPLC-TOFMS) with multivariate data analysis. A total of 16 mass/retention time pairs yielded 13 metabolites of (±)-arecoline 1-oxide, most of them novel. Identity of metabolites was confirmed by tandem mass spectrometry. The principal pathways of metabolism of (±)-arecoline 1-oxide were mercapturic acid formation, with catabolism to mercaptan and methylmercaptan metabolites, apparent C C double-bond reduction, carboxylic acid reduction to the aldehyde (a novel pathway in mammals), N-oxide reduction, and de-esterification. Relative percentages of metabolites were determined directly from the metabolomic data. Approximately, 50% of the urinary metabolites corresponded to unchanged (±)-arecoline 1-oxide, 25% to other N-oxide metabolites, while approximately, 30% corresponded to mercapturic acids or their metabolites. Many metabolites, principally mercapturic acids and their derivatives, were excreted as diastereomers that could be resolved by UPLC-TOFMS. Arecoline was converted to arecoline 1-oxide in vitro by human flavin-containing monooxygenases FMO1 ( K M: 13.6 ± 4.9 μM; V MAX: 0.114 ± 0.01 nmol min −1 μg −1 protein) and FMO3 ( K M: 44.5 ± 8.0 μM; V MAX: 0.014 ± 0.001 nmol min −1 μg −1 protein), but not by FMO5 or any of 11 human cytochromes P450. This report underscores the power of metabolomics in drug metabolite mining.

The Active Role of the Water Solvent in the Regioselective CO Hydrogenation of Unsaturated Aldehydes by [RuH2(mtppms)x] in Basic Media

The regioselective hydrogenation of cinnamaldehyde in basic aqueous media catalyzed by [RuH2(mtppms)x] [x = 3,4; mtppms = meta-sulfonatophenyl-diphenylphosphine] is analyzed by means of theoretical calculations. The water solvent is modeled by the inclusion of a (H2O)3 cluster in addition to a continuum model. Two Ru complexes are evaluated as active species for the reduction process: the major identified species [RuH2P4] and the related phosphine dissociated complex [RuH2P3]. Several reaction mechanisms are computationally evaluated, and their analysis suggests that the reaction takes place in several steps. The first hydrogenation process takes place by means of a hydrogen transfer from the metal catalyst, whereas the second hydrogenation process is performed by a water solvent molecule. This mechanism can account for the selectivity of the CO versus CC double bond reduction experimentally observed under basic reaction conditions and can be directly related to the mechanism found in acidic media, where...

Biosynthesis of bile acids in mammalian liver

The biosynthesis of bile acids in mammalian liver and its regulation, together with the physiological role of bile acids, are reviewed in this article. Bile acids are biosynthesized from cholesterol in hepatocytes. Several steps are involved including epimerisation of the 3beta-hydroxyl group, reduction of the delta4 double bond to the 5beta-H structural arrangement, introduction of alpha-hydroxyl groups at C7 or C7 and C12 and, finally, oxidative degradation of the side chain by three carbon atoms. This gives the primary bile acids, cholic and chenodeoxycholic acids. Cholesterol-7alpha-hydroxylation is the rate determining step in the biosynthesis of cholic and chenodeoxycholic acids. Feedback regulation of cholesterol biosynthesis occurs by various mechanisms including termination of the synthesis of specific cytochromes P-450, modulation of specific cytosol proteins, short-term changes in the process of phosphorylation-dephosphorylation and changes in the capacity of the cholesterol pool as a substrate. Prior to being exported from the liver, bile acids are conjugated with glycine and taurine to produce the bile salts. After excretion into the intestinal tract, primary bile acids are partly converted to secondary bile acids, deoxycholic and lithocholic acids, by intestinal microorganisms. The majority of bile acids is absorbed from the intestinal tract and returned to the liver via the portal blood, so that only a small fraction is excreted in the feces. Bile acids returned to the liver can be reconjugated and reexcreted into the bile in the process of enterohepatic recycling. In addition to the physiological function of emulsifying lipids in the intestinal tract, bile acids are particularly important in respect of their ability to dissolve and transport cholesterol in the bile.

Design and Synthesis of 12‐Aza‐Epothilones (Azathilones)—“Non‐Natural” Natural Products with Potent Anticancer Activity

Design and Synthesis of 12‐Aza‐Epothilones (Azathilones)—“Non‐Natural” Natural Products with Potent Anticancer Activity

Asymmetric Synthesis of Fluorinated Cyclic β-Amino Acid Derivatives through Cross Metathesis

The asymmetric synthesis of several fluorinated cis-2-aminocycloalkane carboxylic acids (cis-2-ACACs) with a cross metathesis (CM) reaction as the key step has been carried out, constituting the first time a metathesis protocol has been undertaken with fluorinated imidoyl chlorides. Subsequent chemoselective hydrogenation of the olefin moiety, Dieckmann condensation, and stereoselective reduction of the iminic double bond afforded the corresponding beta-amino esters with several ring sizes. The asymmetric version of the process was achieved by using (-)-8-phenylmenthol as a chiral auxiliary.

Immobilized tyrosinase reactor for on-line HPLC application: Development and characterization

Mushroom tyrosinase was covalently bonded with glutaraldehyde, as activating agent, to aminopropyl-controlled pore glass support by “in situ” immobilization technique. The Schiff's base double bond reduction with sodium cyanoborohydride was made as innovation. Catalytic activity and stability of the chromatographic reactor were evaluated using d,l-3,4-dihydroxyphenylalanine as substrate. The tyrosinase-IMER was characterized by investigation of various parameters influencing the enzymatic activity (pH, temperature, ionic strength and organic solvents). In addition kinetic measurements showed that, by removal of the external diffusional limitation, the enzyme selectivity towards substrate was improved whereas the activity was comparable with respect to that of free enzyme.

A Metabolomic Approach to the Metabolism of the Areca Nut Alkaloids Arecoline and Arecaidine in the Mouse

The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine. Approximately 600 million users of areca nut products, for example, betel quid chewers, are exposed to these alkaloids, principally arecoline and arecaidine. Metabolism of arecoline (20 mg/kg p.o. and i.p.) and arecaidine (20 mg/kg p.o. and i.p.) was investigated in the mouse using a metabolomic approach employing ultra-performance liquid chromatography-time-of-flight mass spectrometric analysis of urines. Eleven metabolites of arecoline were identified, including arecaidine, arecoline N-oxide, arecaidine N-oxide, N-methylnipecotic acid, N-methylnipecotylglycine, arecaidinylglycine, arecaidinylglycerol, arecaidine mercapturic acid, arecoline mercapturic acid, and arecoline N-oxide mercapturic acid, together with nine unidentified metabolites. Arecaidine shared six of these metabolites with arecoline. Unchanged arecoline comprised 0.3-0.4%, arecaidine 7.1-13.1%, arecoline N-oxide 7.4-19.0%, and N-methylnipecotic acid 13.5-30.3% of the dose excreted in 0-12 h urine after arecoline administration. Unchanged arecaidine comprised 15.1-23.0%, and N-methylnipecotic acid 14.8%-37.7% of the dose excreted in 0-12 h urine after arecaidine administration. The major metabolite of both arecoline and arecaidine, N-methylnipecotic acid, is a novel metabolite arising from carbon-carbon double-bond reduction. Another unusual metabolite found was the monoacylglyceride of arecaidine. What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known. However, the enhanced understanding of the metabolic transformation of arecoline and arecaidine should contribute to further research into the clinical toxicology of the areca alkaloids.