Fukiic Acid Research Articles

A BAHD hydroxycinnamoyltransferase from Actaea racemosa catalyses the formation of fukinolic and cimicifugic acids.

The nucleotide sequence of a BAHD hydroxycinnamoyltransferase was amplified from Actaea racemosa (Ranunculaceae) and expressed in E. coli. The protein catalysed the formation of cimicifugic acids and thus is named hydroxycinnamoyl-CoA:piscidic acid hydroxycinnamoyltransferase (ArHPT1; cimicifugic acid synthase). Actaea racemosa (syn. Cimicifuga racemosa) is known to contain triterpene lactone glycosides and cimicifugic acids. The latter are esters of various hydroxycinnamic or benzoic acids with piscidic or fukiic acid. Amplification of a nucleotide sequence from A. racemosa, that was already known as HCT1 from an EST approach, and its expression in E. coli resulted in a protein that was able to catalyse the formation of several cimicifugic acids. For the characterisation of this hydroxycinnamoyltransferase (hydroxy)cinnamoyl-coenzyme A thioesters were synthesised as donor substrates and piscidic acid isolated as acceptor substrate. The lowest Km-value with 6.8µM was determined for p-coumaroyl-CoA. More than 30 possible acceptor substrates were tested, but only piscidic acid and putatively fukiic acid were accepted. The apparent Km-value for piscidic acid was 32.3µM. High expression of the hydroxycinnamoyltransferase gene was found in roots, but the content of cimicifugic acids was higher in leaves and flowers than in roots. This work describes for the first time a biosynthetic step in the formation of cimicifugic acids catalysed by a so far uncharacterised hydroxycinnamoyltransferase accepting piscidic acid as acceptor substrate thus being a hydroxycinnamoyl-CoA:piscidic acid hydroxycinnamoyltransferase (ArHPT1; cimicifugic acid synthase).

Structure-Guided Identification of Novel Phenolic and Phenolic Amide Allosides from the Rhizomes of Cimicifuga heracleifolia

Two phenolic allopyranosides and two phenolic amide allopyranosides, along with eight known phenolic compounds, including cimicifugic acids, shomaside B, fukiic acid, isoferulic acid, and piscidic acid, were isolated from the n-butanolic extract of rhizomes of Cimicifuga heracleifolia. On-line spectroscopic data for UV, NMR, and MS from a combination of LC-NMR and LC-MS techniques directly and rapidly provided sufficient structural information to identify and confirm all the structures of major phenolic compounds in the extract, in addition to their HPLC profiles. This combined analytic information was then used as a dereplication tool for structure-guided screening in order to isolate unknown phenolic compounds in the extract. Successive fractionation and purification using semi-preparative HPLC acquired four unknown allopyranosides, and their structures were identified as cis-ferulic acid 4-O-β-D-allopyranoside, trans-ferulic acid 4-O-β-D-allopyranoside, trans-feruloyltyramine 4-O-β-D-allopyranoside, and trans-feruloyl-(3-O-methyl)dopamine 4-O-β-D-allopyranoside, based on a subsequent spectroscopic interpretation.

Hyaluronidase Inhibitors from “Cimicifugae Rhizoma” (a Mixture of the Rhizomes of Cimicifuga dahurica and C. heracleifolia)

From the 80% acetone extract of "Cimicifugae Rhizoma" (a mixture of Cimicifuga dahurica and C. heracleifolia used medicinally), seven new fukiic acid derivatives (1-7) and a new phenylethanoid derivative (8) were isolated along with eight known compounds (9-16). Fukinolic acid (9) and cimicifugic acids A-J (10-16, 5-7) showed stronger hyaluronidase inhibitory activities than the positive control, rosmarinic acid.

The total synthesis of fukiic acid, an HIV-1 integrase inhibitor

A successful synthesis of fukiic acid is described in 7% overall yield (6 steps from veratraldehyde). rac-Fukiic acid was found to be a potent inhibitor of HIV-1 integrase but did not reveal any antiviral activity in the MT-4 cells assay.

Phenolic Esters from the Rhizomes ofCimicifuga racemosado not Cause Proliferation Effects in MCF-7 Cells

Five phenylpropanoid esters, caffeoylglycolic acid, 2-caffeoylpiscidic acid (cimicifugic acid D), 3,4-dihydroxyphenacyl caffeate (petasiphenone), 3,4-dihydroxyphenyl-2-oxopropyl isoferulate (cimiciphenol) and 3,4-dihydroxyphenacyl isoferulate (cimiciphenone) were isolated from a commercially available extract of the rhizomes of Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L.) for the first time; the known cimicifugic acids A, B, E, F, fukinolic acid, fukiic acid and caffeic acid were also obtained. Cimiciphenone and caffeoylglycolic acid are new natural products. The structures were elucidated by means of spectroscopic data (ESI-MS, 1H-, 13C-NMR, COSY, HMQC, HMBC and NOE experiments). Ferulic acid and isoferulic acid were detected by HPLC analysis in comparison to standards. The estrogenic activity of the isolated compounds was tested in an estrogen-dependent MCF-7 mamma carcinoma cell line; 17beta-estradiol (10(-11) M) and the phytoestrogen coumestrol (10(-7) - 10(-5) M) were used as references. The results suggest that, in contrast to an earlier report, the phenolic esters do not exert a proliferative (estrogenic) effect in this test system.

Biosynthesis of Fukinolic Acid Isolated fromPetasites japonicus

The biosynthesis of fukinolic acid, which had been isolated from the Japanese fuki vegetable, Petasites japonicus, was investigated by feeding selected (13)C-labeled compounds to axenic cultures of P. japonicus. [1,2-(13)C(2)] sodium acetate and [1-(13)C] L-tyrosine were incorporated into the fukiic acid sub group, while [3-(13)C] L-phenylalanine was incorporated into the caffeic acid moiety.

Effects of fukinolic acid and cimicifugic acids from Cimicifuga species on collagenolytic activity.

The inhibitory collagenolytic activity (47-64% inhibition in 0.22-0.24 microM) of fukinolic acid and cimicifugic acids A, B, and C, which are esters of fukiic acid (3',4'-dihydroxybenzyl tartaric acid) was more potent than that (20-37% inhibition in 0.23-0.24 microM) of cimicifugic acids D, E, F, which are esters of pscidic acid (4'-hydroxybenzyl tartaric acid). Since fukiic acid showed weaker inhibition, and caffeic acid, ferulic acid, isoferulic acid, and p-coumaric acid showed far weaker activities, the entire structures of fukinolic acid and cimicifugic acids A, B, and C proved to be responsible for the inhibitory activities. Trypsin and pronase E hydrolyzed collagen nonselectively alone or in addition to collagenase. These collagenolytic activities were also inhibited by fukinolic acid. These results show that fukinolic acid may inhibit either the collagenolytic activities specific to collagenase or nonspecific to other emzymes. The present studies suggest the potential effect of fukinolic acid and cimicifugic acids of Cimicifuga rhizomes in preventing collagen degradation by collagenases or collagenolytic enzymes under pathological conditions, wound healing, or inflammation.

Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid.

Hydroxycinnamic acid esters of fukiic acid and piscidic acid were isolated from a 50% ethanolic extract obtained from the rhizomes of Cimicifuga racemosa (Ranunculaceae). Besides 2-E-caffeoylfukiic acid (fukinolic acid), 2-E-feruloylfukiic acid (cimicifugic acid A), 2-E-isoferuloylfukiic acid (cimicifugic acid B), 2-E-feruloylpiscidic acid (cimicifugic acid E) and 2-E-isoferuloylpiscidic acid (cimicifugic acid F), free caffeic, ferulic and isoferulic acids were isolated. The estrogenic activity of fukinolic acid was shown by increased proliferation (126% at 5 x 10(-8) M) of an estrogen dependent MCF-7 cell system with reference to estradiol (120% at 10(-10) M).

Piscidic acid and fukiic acid esters from Cimicifuga simplex1Part 24 in the series “Constituents of Cimicifuga spp.”, and Part 2 in the series “Phenolics of Cimicifuga spp.” For part 23 see Ref.[1].1

Investigation of the underground parts of Cimicifuga simplex afforded five new piscidic acid esters and two new fukiic acid esters: 2-caffeoyl piscidic acid, 2-feruloyl piscidic acid, 2-isoferuloyl piscidic acid, 2-feruloyl piscidic acid-1-methyl ester, 2-isoferuloyl piscidic acid-1-methyl ester, 2-feruloyl fukiic acid-1-methyl ester, and 2-isoferuloyl fukiic acid-1-methyl ester.

Three New Fukiic Acid Esters, Cimicifugic Acids A, B and C, from Cimicifuga Simplex WORMSK.

Three new fukiic acid esters, cimicifugic acids A (1), B (2), and C (3), were isolated along with fukinolic acid (4), fukiic acid (5), caffeic acid (6), ferulic acid (7), isoferulic acid (8), 3, 4-dimethoxycinnamic acid (9) and p-coumaric acid (10) from Cimicifuga simplex. Their structures were identified as 2-feruloyl, 2-isoferuloyl, and 2-p-coumaroyl fukiic acid (1-3) on the basis of spectroscopic and chemical data.

Vasoactive effects of cimicifugic acids C and D, and fukinolic acid in cimicifuga rhizome.

Vasoactive effects of cimicifugic acids A-E, fukinolic acid and fukiic acid isolated from Cimicifuga plants were investigated using rat aortic strips. Cimicifugic acid D and fukinolic acid at 3x10(-4) M caused a sustained, slowly developing relaxation of aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium. Cimicifugic acid C inversely caused a weak contraction. Cimicifugic acids A, B and E and fukiic acid showed no vasoactivity at 3x10(-4) M. Cimicifugic acids A-E and fukinolic acid are esters between cinnamic acids and the hydroxyl group of benzyltartaric acids. For the manifestation of vasoactivity in the rat aorta, it is concluded that in the cinnamic acid moiety, a caffeoyl group might be necessary for the relaxation activity, and the p-coumaroyl group causes contraction. Concentration response curves for the Ca2+-induced contracture of depolarized aortic strips with isotonic high K+ were not affected by cimicifugic acid D or fukinolic acid. The Ca2+-induced contraction of aortic strips, preincubated with 10(-6) M NE in the presence of 10(-6) M nicardipine and 0.01 mM EGTA in Ca2+-free solution, were inhibited by cimicifugic acid D and fukinolic acid. These results indicated that the inhibition by cimicifugic acid D and fukinolic acid of the NE-induced contraction of rat aorta are attributable to the suppression of Ca2+ influx from the extracellular space enhanced by NE.

Studies on inhibitory activities of fukiic acid esters on germination, alpha-amylase and carboxypeptidase A.

Fukinolic acid (1) and cimicifugic acid A (2), caffeic acid analogs, as well as rosmarinic acid (3) and caffeic acid (4) showed inhibition on seed germination and seedling growth. The potency of 1 and 2 was comparable with that of 3. Compounds 1 and 2 also showed strong inhibitory activities as well as 3 and 4 on alpha-amylase. The activity of 1 was higher than that of acarbose used as a positive control, and its 50% inhibitory concentration (IC50) was 2.41 x 10(-5) M. Compounds 1 and 2 also showed inhibitory activities strong as 3 and stronger than 4 on carboxypeptidase A. The activities of 1 and 2 were higher than that of 1, 10-phenanthroline used as a positive control.

Fukiinsäure und 3′‐O‐Methyl‐fukiinsäure, zwei phenolische Hydroxycarbonsäuren aus Piscidia Erythrina

AbstractPurification of crude piscidic acid from ‘Cortex Piscidiae Erythrinae’, the root bark of Piscidia Erythrina L. (Papilionaceae), led to the isolation of fukiic acid (5) and 3′‐O‐methyl‐fukiic acid (8). Since partition chromatography with alcoholic solvents produced the corresponding half‐esters as artefacts, the acids were transformed to their methyl esters before separation. Spectroscopic methods and comparison with authentic samples from Petasites japonicus F. SCHMIDT (Compositae) confirmed the structures 5 and 8.

The Stereochemistry of Fukiic Acid and Its Correlation with Piscidic Acid

The stereochemistry of fukiic acid (I) was elucidated. The relative configuration was determined to be erythro by IR spectrum and the evidence of acetonide formation. The absolute configuration of fukiic acid was assigned as S-configuration at C–2 and R-configuration at C–3, by Horeau’s method and the identification of ozonolysis product to be hibiscus acid (10 a).

The Stereochemistry of Fukiic Acid and Its Correlation with Piscidic Acid

The Stereochemistry of Fukiic Acid and Its Correlation with Piscidic Acid

The Constituents of Petasites japonicus: Structures of Fukiic Acid and Fukinolic Acid

A major polyphenol from P. japonicus, named fukinolic acid (XII), was isolated and its structure was investigated. Fukinolic acid afforded a new polyphenol named fukiic acid (I) and caffeic acid on hydrolysis in molar ratio 1:1. The structure of fukiic acid was established as 2,3-dihydroxy-4-(3′,4′-dihydroxyphenyl)-3-carboxybutyric acid (I), and its methyl derivatives were described.Based on evidences presented, the structure for fukinolic acid was proposed as XII. It was further demonstrated that fukinolic acid caused the brown discoloration on action of a polyphenoloxidase from the plant tissues.

The Synthesis and Configuration of Fukiic Acid Derivatives

Abstract The methylation of 3,4-dimethoxyphenylpyruvic acid (II) gave the corresponding methyl ester (III), which was then subjected to a Wittig reaction with carbomethoxymethylenetriphenylphosphorane to give the corresponding fumaric (IVa) and maleic (IVb) acid derivatives in a 1:3 ratio. The cis-hydroxylation of IVa and IVb with an aqueous solution of potassium permanganate and magnesium sulfate gave methyl (±)-thero-2,3-dihydroxy-4-(3,4-dimethoxyphenyl)-3-methoxycarbonylbutyrate (Va) and its (±)-erythro-isomer (Vb) respectively. The dimethyl esters, (±)-Va and (±)-Vb, were converted to the corresponding monomethyl esters, (±)-VIIa and (±)-VIIb respectively, via two dicarboxylic acid derivatives, (±)-VIa and (±)-VIb. The resolution of (±)-VIIb with brucine gave (+)-VIIb and (−)-VIIb, which were then converted to (+)-Vb and (+)-VIb and to (−)-Vb and (−)-VIb respectively. The synthetic (+)-Vb was shown to be identical with the natural O,O′-dimethylfukiic acid dimethyl ester by a mixed fusion and by comparisons of their IR and NMR spectra. From the present study it is evident that natural fukiic acid has an erythro configuration.

The stereochemistry of fukiic acid and piscidic acid.

The stereochemistry of fukiic acid and piscidic acid.

Fukiic Acid Isolated from the Hydrolysate of a Polyphenol in Petasites japonicus

Journal Article Fukiic Acid Isolated from the Hydrolysate of a Polyphenol in Petasites japonicus Get access Sadao Sakamura, Sadao Sakamura Department of Agricultural Chemistry, Hokkaido University, Sapporo Search for other works by this author on: Oxford Academic Google Scholar Teruhiko Yoshihara, Teruhiko Yoshihara Department of Agricultural Chemistry, Hokkaido University, Sapporo Search for other works by this author on: Oxford Academic Google Scholar Katsuhiko Toyoda Katsuhiko Toyoda Department of Agricultural Chemistry, Hokkaido University, Sapporo Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 33, Issue 12, 1 December 1969, Pages 1795–1797, https://doi.org/10.1080/00021369.1969.10859543 Published: 01 December 1969 Article history Received: 02 September 1969 Published: 01 December 1969