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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.

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 (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.

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.

Purification 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.

Fukiic acid derivatives have been synthesized from 3,4-dimethoxyphenylpyruvic acid by a stereospecific method. The synthetic methyl (+)-erythro-2,3-dihydroxy-4-(3,4-climethoxyphenyl)-3-methoxycarbonylbutyrate was shown to be identical with natural O,O′-dimethylfukiic acid dimethyl ester by a direct comparison.

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 ...

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 ...