Dihydrocinnamic Acid Research Articles

A Mixed-Ligand Approach Enables the Asymmetric Hydrogenation of an α-Isopropylcinnamic Acid en Route to the Renin Inhibitor Aliskiren

An asymmetric hydrogenation process for the α-isopropyl dihydrocinnamic acid derivative 2, an intermediate for the renin inhibitor aliskiren (4), has been developed using a rhodium catalyst ligated with a chiral monodentate phosphoramidite and a nonchiral phosphine. Whereas catalysts based on two equivalents of monodentate phosphoramidites gave promising results, the rate of hydrogenation and ee of the product could be improved spectacularly by the addition of monodentate nonchiral triarylphosphines to these catalysts. This remarkable mixed-ligand catalyst has been identified using high-throughput experimentation. With the best catalysts turnover numbers >5000 mol mol-1, turnover frequencies >1000 mol mol-1 h-1, and ee's up to 95% have been achieved.

Structure‐based design, Fourrier transformed infrared and Raman studies and structure‐activity relationships of synthetic peptides with trans/cis‐cinnamic and dihydrocinnamic acids as inhibitors for thrombin

As a part of a research proposal aimed at studying structure activity relationship in the field of peptides inhibitors for thrombin, we performed molecular docking experiments using the software “SCULPT” (from MDL) and designed “in silico” libraries of peptides as potential inhibitors for thrombin. Our original experiments generated a candidate group of peptides (with both L- and D- amino acids) that were characterized by a predicted free energy based on Van der Waals interactions with thrombin in the range from −20 to −100 kcal/mol. New peptides containing phenylalanine (Phe) analogs such as (trans/cis)cinnamic and dihydrocinnamic acids were designed to scan the P3 position in the sequence space D-Phe (P3)–Pro(P2)–D-Arg(P1)-P1′-CONH2 which was shown to inhibit reversibly thrombin in vitro. The P1′ position contains the most conserved L-amino acids found in the natural substrates of thrombin such as Gly, Ile, Ala, Cys and Ser. The cis-cinnamoyl peptides were obtained from trans-cinnamoyl peptides by exposing the solution of trans-cinnamoyl peptide to UV-light (354 nm) for 5 minutes. Fourier transform-infrared (FTIR) and Raman microsspectroscopy of solid peptide films were used to determine the conversion of trans-cinnamoyl peptides into cis-cinnamoyl peptides. The in vitro thrombin inhibition assays showed that transcinnamoyl peptides are stronger inhibitors than cis-cinnamoyl and dihydrocinnamoyl-peptides with inhibitory constants in the range of 1-200 uM.

Chemical Constituents of the Aquatic Plant Schoenoplectus lacustris: Evaluation of Phytotoxic Effects on the Green Alga Selenastrum capricornutum

Forty-nine secondary metabolites were isolated from aqueous and alcoholic extracts of the aquatic plant Shoenoplectus lacustris. All compounds were characterized based on spectroscopic data. Eleven free and glycosylated low-molecular polyphenols, 17 cinnamic acid and dihydrocinnamic acid derivatives, 11 flavonoids, and 10 C13 nor-isoprenoids were identified. The structure of the new compound, 1-benzoyl-glycerol-2-alpha-L-arabinopyranoside, was elucidated by 2D NMR experiments (COSY, HSQC, HMBC, NOESY). To evaluate potential phytotoxic effects, all compounds were tested on the green alga Selenastrum capricornutum, a unicellular organism commonly used in tests of toxicity as a bioindicator of eutrophic sites. The most active compound was (-)-catechin, showing an inhibition similar to that of the algaecide CuSO4.

A concise synthesis of polyhydroxydihydrochalcones and homoisoflavonoids

A general and single step synthesis of polyhydroxydihydrochalcones from the readily available phenols and dihydrocinnamic acids using BF 3·Et 2O is described. The method allows the synthesis of a wide range of compounds with multiple phenolic hydroxyls and other substituents. These dihydrochalcones are converted into homoisoflavonoids by DMF/PCl 5 and the methodology has been applied to the synthesis of naturally occurring phloretin and 5,7-dihydroxy-3-[(4-hydroxyphenyl)methyl]-4 H-chromen-4-one. The antioxidant activity of dihydrochalcones and homoisoflavonoids was determined by superoxide free radical (NBT) and DPPH free radical scavenging methods. Polyhydroxydihydrochalcones 3c , 3f , 3g and homoisoflavonoids 4c , 4f , 4g displayed excellent antioxidant activity.

Divergence of secondary metabolism in cell suspension cultures and differentiated plants of Piper cernuum and P. crassinervium

The secondary metabolism in the leaves of P. cernuum produces cinnamic and dihydrocinnamic acid derivatives and the lignan cubebin. In case of P. crassinervium flavonoids and prenylated hydroquinones were characterized as major compounds. The cell cultures showed the production of the phenylethylamines dopamine and tyramine in P. cernuum, while in case of P. crassinervium four alkamides were isolated as major compounds, including the new 2,3,4-trimethoxy-N-methyl-aristolactam and 3-hydroxy-2-methoxy-N-methyl-aristolactam.

Composição química de Baccharis dracunculifolia, fonte botânica das própolis dos estados de São Paulo e Minas Gerais

A própolis é uma substância resinosa coletada pelas abelhas de diversas partes das plantas. Sua composição depende da época, vegetação e local de coleta. Análises fitoquímicas de própolis produzidas de Baccharis dracunculioflia (alecrim-do-campo) por abelhas Apis mellifera africanizada nos estados de São Paulo e Minas Gerais foram feitas por espectrofotometria na região U.V.-Visível, CCDAE-FR, CLAE-FR e CG-EM. Uma característica dos compostos fenólicos das própolis analisadas e da espécie vegetal de B. dracunculiofolia foi a alta proporção de artepilin C e outros derivados do ácido cinâmico. Com base nas evidências fitoquímicas, B. dracunculifolia foi identificada como a principal fonte vegetal das própolis produzidas nos estados de São Paulo e Minas Gerais.

Dihydrocinnamic acids in Pteridium aquilinum

Dihydro- p-coumaric (phloretic) and dihydroferulic acids have been identified in Pteridium aquilinum. Whereas the latter has been located in cyanogenic and acyanogenic plants, the first has only been detected in cyanogenic forms.

Anti-emetic Principles of Water Extract of Brazilian Propolis

ABSTRACTWater extract of Brazilian propolis showed anti-emetic activity on copper sulfate–induced emesis in young chicks. Bioassay-guided fractionation of the extract was carried out, and dehydrohautriwaic acid (1), (E.)-3-(2,2-dimethyl-2H.-1-benzopyran-6-yl)-2-propenoic acid (2), dihydrocinnamic acid (3), (Z.)-3-(2,2-dimethyl-2H.-1-benzopyran-6-yl)-2-propenoic acid (4), aromadendrane-4β,10α-diol (5), and lupeol (6) were isolated as the active components.

Tetranortriterpenoids and Dihydrocinnamic Acid Derivatives from Hortia colombiana

A novel tetranortriterpenoid and two dihydrocinnamic acid derivatives were obtained from the wood of Hortia colombiana. Their structures were elucidated by detailed NMR investigations and the relative configurations established by Difference NOE experiments. In addition, alloxanthoxyletin, nerolidol, epoxynerolidol, three known dihydrocinnamic acid derivatives and two amides were isolated. Detailed analysis of NMR data of Hortiolide A, whose structure was previosly established by X ray, are also provided.

A polar effects controlled enantioselective 1,2-chlorine atom migration via a chlorine-bridged radical intermediate.

An enantioselective 1,2-chlorine atom migration was observed in the tributyltin hydride reduction of various dihalogenated dihydrocinnamic acid derivatives. It is proposed that the reduction involves the formation of a chlorine-bridged radical intermediate, followed by hydrogen atom transfer to either the beta- or the alpha-carbon. The product distribution is affected by electron-withdrawing groups in that hydrogen atom transfer to the proximate carbon is favored. Presumably, this is due to the transition state of the hydrogen delivery step being electron rich, due to the relatively electropositive tin radical. These results demonstrate a 1,2-chlorine atom migration reaction governed by polar effects.

Prenylated Coumarins, Chalcone and New Cinnamic Acid and Dihydrocinnamic Acid Derivatives from Brosimum gaudichaudii

Three new natural cinnamic acid and dihydrocinnamic acid derivatives were isolated from the roots of Brosimum gaudichaudii, in addition to fourteen known substances (ten coumarins, one chalcone, b-sitosterol, 3b-O-b-D-glucopyranosylsitosterol and b-amyrin). The structures were established by spectral data, including analysis of 2D-NMR experiments and mass spectra. All aromatic compounds have 4-hydroxy-3-prenylcinnamic acid as a common precursor. The new substances are derived from a precursor of the coumarins, which through an O-methylation lost its ability to form the lactone ring.

Effect of overexpression of Saccharomyces cerevisiae Pad1p on the resistance to phenylacrylic acids and lignocellulose hydrolysates under aerobic and oxygen-limited conditions

Lignocellulose hydrolysates, obtained by acid hydrolysis for production of bioethanol, contain, in addition to fermentable sugars, compounds that inhibit the fermenting micro-organism. One approach to alleviate the inhibition problem is to use genetic engineering to introduce increased tolerance. Phenylacrylic acid decarboxylase (Pad1p) catalyses a decarboxylation step, by which aromatic carboxylic acids are converted to the corresponding vinyl derivatives. Pad1p-overexpressing Saccharomyces cerevisiae was cultivated in synthetic medium in the presence of model compounds, ferulic acid [(2 E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid] and cinnamic acid [(2 E)-3-phenylprop-2-enoic acid], as well as in a dilute acid hydrolysate of spruce to examine the resistance against fermentation inhibitors. Overexpression of S. cerevisiae phenylacrylic acid decarboxylase (Pad1p) resulted in an improved growth rate and ethanol productivity in the presence of ferulic acid, cinnamic acid, and in a dilute acid hydrolysate of spruce. Vinyl guaiacol (2-methoxy-4-vinylphenol) was identified as a major metabolite of ferulic acid, and dihydroferulic acid [3-(4-hydroxy-3-methoxyphenyl)propanoic acid] was detected under oxygen-limited conditions. Styrene (vinylbenzene) and dihydrocinnamic acid (3-phenylpropanoic acid) were identified as metabolites of cinnamic acid. Transformants overexpressing Pad1p had the ability to convert ferulic and cinnamic acid at a faster rate than a control transformant (PAD(C)) not overexpressing Pad1p. This enabled faster growth for Pad1p-overexpressing transformants under both aerobic and oxygen-limited conditions. Pad1p activity was also studied using non-growing cells. The overexpressing transformants showed approximately tenfold higher activity than PAD(C). The Pad1p overexpressing transformants also showed a 22-25% faster glucose consumption rate, a 40-45% faster mannose consumption rate, and a 24-29% faster ethanol production rate in the dilute acid hydrolysate of spruce.

Phenylpropanoid interconversion in Anigozanthos preissii observed by high-performance liquid chromatography-nuclear magnetic resonance spectroscopy.

HPLC-NMR spectroscopy was employed to observe isotopically labelled intermediates of the phenylpropanoid metabolism in Anigozanthos preissii. Hydroxylation of dihydrocinnamic acid to dihydro-p-coumaric acid and the reversible interconversion between phenylpropanoids and phenylpropenoids were detected, suggesting the operation of a metabolic network in early phenylpropanoid biosynthesis in this plant.

New phenolic antioxidants of PYA and PYE class increase the resistance S. cerevisiae strain SP4, its SOD- and catalase-deficient mutants to lipophilic oxidants.

Was demonstrate the protection ability against reactive oxygen species afforded to S. cerevisiae (wild-type strain SP4 and its mutants deficient in major antioxidant enzymes--catalase T and A, CuZnSOD) by PYA and PYE, new groups of phenolic antioxidants (quaternary ammonium salts of dihydrocinnamic acid amino esters with different alkyl chains; synthesized in this laboratory). The survival of strains exposed to the lipophilic oxidation inducers tert-butyl hydroperoxide (TBHP) and 1,1'-azobis(4-cyclohexane carbonitrile) (ACCN) with or without antioxidant pretreatment was determined by plating. S. cerevisiae mutant deficient in SOD was found to be hypersensitive to TBHP and ACCN while the sensitivity of the strain deficient in catalase T and A was about the same as in the wild-type strain. A 1-h preincubation of cells of both the wild-type and the mutant strains with the phenolic antioxidants prior to exposure to TBHP or ACCN substantially increased the cell survival. The magnitude of protection depended on the strain and the length of the alkyl chain of the antioxidant; the best average protection against TBHP was provided by PYE and PYA compounds with 12- and 16-membered alkyl chains whereas PYE-8 and PYA-12 derivatives afforded the best average protection against ACCN.

Coumarins and dihydrocinnamic acid derivatives from Micromelum falcatum

Besides the known coumarins microminutinin and 6-methoxymicrominutinin, the new dihydrocinnamic acid derivatives 3,4-dihydro-1,2- secomicrominutinin, 3,4-dihydro-1,2- secomicrominutinin methylester and 3,4-dihydro-1,2- secomicrominutinin-9- O-glucoside as well as the new 8-prenylated coumarin microfalcatin isovalerate were isolated from the leaves of Micromelum falcatum (Rutaceae). The structures were elucidated by mass and NMR spectroscopy. The relative configuration of microfalcatin isovalerate was established as 1′,2′- threo by analysis of the NOE effects of its acetonide.

Dihydrocinnamic acids are involved in the biosynthesis of phenylphenalenones in Anigozanthos preissii

Feeding experiments using root cultures of Anigozanthos preissii and NMR spectroscopical studies revealed reversible interconversion between phenylpropanoids and dihydrophenylpropanoids, and their incorporation into phenylphenalenones. Multiply labelled dihydrocinnamic acid was transformed to coumaric acid and further metabolized to 2-hydroxy-9-(4-hydroxyphenyl)- 1H -phenalen-1-one (hydroxyanigorufone). 13 C NMR spectroscopy and HPLC- 1 H NMR coupling were employed to detect trace amounts of multiply labelled biosynthetic intermediates and further metabolites. The pathway of the phenylphenalenone biosynthesis is discussed.

3,4,8-Trimethoxy-2-quinolone: A New Alkaloid from Eriostemon gardneri

A new alkaloid, 3,4,8-trimethoxy-2quinolone (l), and six known com- pounds including TWO pyranocoumarins, avicennol and cis-avicennol, two dihydrocinnamic acid derivatives, eriostemoic acid and eriostoic acid, and two flavonoid glycosides, hesperidin and diosmin, have been isolated from the aerial parts of Eriostemon gardneri. Eriostemon gardneri P.G. Wilson (Rutaceae), an undershrub found near the south coast from Cheyne Bay east to beyond Esperance, and north towards Lake King in Western Australia, is one of eighteen species placed in Eriostemon sect. Nigrostipulae (1-3). As part of our phy- tochemical survey on the genus Eriosremon (Pb), we wish to report on the major secondary metabolites found in a sample of the aerial parts of Eriostemon gardnwi. Seven compounds were isolated and characterized as 3,4,8-trimethoxy-2- quinolone El), avicennol (7,8), cis-

Pyranocoumarins from Eriostemon apiculatus

An examination of the aerial parts of Eriostemon apiculatus has shown it to contain the uncommon pyranocoumarins avicennol, cis-avicennol, dipetalolactone, avicennin and cis-avicennin. The last of these appears to be novel. The simple coumarin umbelliferone and the dihydrocinnamic acid derivative eriostemoic acid were also isolated. The occurrence of these pyranocoumarins supports the placement of this taxon close to Eriostemon coccineus in Eriostemon sect. Nigrostipulae-A.

New coumarin and dihydrocinnamic acid derivatives from two malaysian populations of Micromelum minutum

Three novel compounds, two compounds and a dihydrocinnamic acid, have been isolated from two collections of Micromelum minutum and identified by means of NMR spectroscopy. A sample collected from Pahang gave the typical coumarin micromelin and a new dihydrocinnamic acid derivative of micromelin which was identified as 1,2- seco-dihydromicromelin. The second sample, collected from Kelantan, gave two new tetracyclic coumarins, microminutinin and 6-methoxymicrominutinin, which possess a fused bifurano system that appears to be derived by cyclization of a 7-oxygenated-8-(1,2-dimethyl)propylcoumarin precursor. The structure of microminutinin is revised from that proposed in a previous paper.

A novel feature in phenyliodine diacetate oxidation

Phenyliodine diacetae (PIDA) oxidation of N-benzyl- N-benzyloxycarbonyltyrosine ( 4a) followed in one pot by quenching with aqueous sodium chloride or bromide solution gave the corresponding dihalodienone lactone ( 5a or 5b). With dihydrocinnamic acid similar feature of PIDA oxidation was obsearved. The plausible mechanism is also described.