Aryltetralol and aryltetralone lignans from Holostylis reniformis

Aryltetralol and aryltetralone lignans were isolated from the hexane extracts of the roots of Holostylis reniformis. Their structures were determined by spectroscopic methods and chemical transformations.     

Aryltetralone lignans and 7,8-seco-lignans from Holostylis reniformis

Aryltetralone lignans and two 7,8-seco-lignans were isolated from the acetone and hexane extracts of the roots of Holostylis reniformis, together with (-)-galbacin. Their structures were determined by spectroscopic methods.     

Further lignoids from Virola sebifera

From the fruits of Virola sebifera 2,3-dibenzylbutanes were isolated together with tetralin and naphthalene neolignans. 2,3-Dimethyl-4-piperonyl-4-veratrylbutan-1-ol, a further constituent, probably arises by a retro-Friedel-Crafts reaction from a tetralin neolignan. An additional component was identified as a dimeric neolignan.     

Biosynthesis of antimalarial lignans from Holostylis reniformis

Holostylis reniformis biosynthesizes 8-8′ linked lignans without 9,9′-oxygenation. To elucidate the biosynthetic pathways to these lignans, the reputed precursors [U-¹⁴C]phenylalanine, [9-³H₁]coniferyl alcohol, and [9-³H₁]isoeugenol were administered to roots of the plant, which led to the incorporation of ³H and ¹⁴C into ten 2,7′ linked-lignans (aryltetralone lignans) and two 7,7′-epoxylignans (furan lignans). These administration experiments demonstrated that the lignans were propenylphenol-derived and that H. reniformis can exhibit regioselective control over radical-radical coupling (via isoeugenol radicals). Regiospecific control over propenylphenol-derived lignan biosynthesis was observed, together with diastereoselective control of C2-C7′ bond formation for the aryltetralone lignans (7′R). These experiments provide evidence that isoeugenol is a biosynthetic intermediate to the aryltetralone and furan lignans.     

Acylresorcinols from Virola sebifera and Virola elongata

The fruits of Virola sebifera and V. elongata (Myristicaceae) contain three ω-phenylundecanoyl-substituted compounds, a 2,6-dihydroxybenzene, a 2,6-dihydroxy-4-methoxybenzene and a 3-hydroxycyclohexan-2,6-dione. Three additional 2,6-dihydroxybenzenes are substituted by hexadecanoyl, hexadec-4Z-enoyl and 8-hydroxyoctadec-4Z-enoyl groups.     

Aryltetralone and arylindanone neolignans from Virola sebifera

The fruits of Virola sebifera contain several tetralone neolignans, including 2,4-dihydroxy-6,7-methylenedioxy-2,3-dimethyl-4-veratryltetralin-1-one. The 3-hydroxylated derivative of this compound may undergo a biosynthetic pinacol-pinacolone rearrangement to give 2-acetyl-3-hydroxy-2-methyl-5,6-methylenedioxy-3-veratrylindan-1-one which, together with other indanone neolignans, was also isolated.     

Neolignans from fruits of Virola elongata

Fruits of Virola elongata contain, besides the furofuranoid lignans eudesmin, epieudesmin and fargesin, the aryl-benzyl-methyl tetrahydrofuran neolignans magnostellins A and C. The absolute configuration of the magnostellins was detennined.     

Furanofuran lignans from Vitex negundo seeds

A new furanofuran lignan, vitelignin A (1), together with eight known lignan derivatives, were isolated from the seeds of Vitex negundo. Their structures were identified as (+)-4-oxo-8-hydroxy-2,6-di(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (1), 4-oxosesamin (2), (+)-sesamin (3), (+)-paulownin (4), 4-hydroxysesamin (5), 4,8-dihydroxysesamin (6), 4-oxopaulownin (7), (+)-2-(3-methoxy-4-hydroxyphenyl)-6-(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (8), and (+)-pinoresinol (9), respectively, based on extensive NMR and MS spectroscopic studies. Compounds 1, 2, and 7 showed moderate antifungal activity in vitro.     

Antioxidant lignans from Larrea tridentata

Three lignans, (7S,8S,7'S,8'S)-3,3',4'-trihydroxy-4-methoxy-7,7'-epoxylignan, meso-(rel 7S,8S,7'R,8'R)-3,4,3',4'-tetrahydroxy-7,7'-epoxylignan, and (E)-4,4'-dihydroxy-7,7'-dioxolign-8(8')-ene, together with 10 known compounds, were isolated from the leaves of Larrea tridentata. The structures of the new compounds were determined primarily from 1D and 2D NMR spectroscopic analysis. Their antioxidant activities against intracellular reactive oxygen species were evaluated in HL-60 cells.     

Nortriterpenoids and lignans from Schisandra sphenanthera

Nortriterpenoids, sphenadilactone C (1) and sphenasin A (2), together with four known lignans (3-6), were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and compound 2 was further confirmed by single-crystal X-ray diffraction. Compound 1 features a partial enol moiety and an acetamide group in its structure. In addition, compounds 1, 3-6 showed weak anti-HIV-1 activity with EC₅₀ values in the range of 15.5-29.5 μg/mL.     

Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC₅₀ values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7′ might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments.     

Trypanocidal tetrahydrofuran lignans from inflorescences of Piper solmsianum

In addition to sitosterol, syringaldehyde, 3,4,5-trimethoxybenzoic acid, isoelemicin and grandisin, two new tetrahydrofuran lignans were isolated from Piper solmsianun and characterized as rel-(7R,8R,7'R,8'R)-3',4'-methylenedioxy-3,4,5,5'-tetramethoxy-7,7'-epoxylignan and rel-(7R,8R,7'R,8'R)-3,4,3',4'-dimethylenedioxy-5,5'-dimethoxy-7,7'-epoxylignan on the basis of spectroscopic data, including 2D NMR spectrometric techniques. Their in vitro activity were determined against the trypomastigote form of Trypanossoma cruzi.     

Two highly oxygenated eudesmanes and 10 lignans from Achillea holosericea

Two new highly oxygenated eudesmanes and 10 known lignans were isolated from the aerial parts of Achillea holosericea. Their structures were elucidated by extensive application of one- and two-dimensional 1H and 13C NMR spectroscopy.     

Cytotoxic lignans from Larrea tridentata

Six lignans, including the cyclolignan 3,4'-dihydroxy-3',4'-dimethoxy-6,7'-cyclolignan, were isolated from the flowering tops of Larrea tridentata. Additionally the flavanone, (S)-4',5-dihydroxy-7-methoxyflavanone, was isolated for the first time from L. tridentata or any member of the family Zygophyllaceae. All of the compounds were assessed for their growth inhibitory activity against human breast cancer, human colon cancer and human melanoma cell lines. The lignans had IC50 values of 5-60 microM with the linear butane-type lignans being the most potent, and it was found that colon cancer cells were the least sensitive cell type tested. The relative potency of linear butane type lignans against human breast cancer appears to correlate positively with the number of O-methyl groups present on the molecule.     

Immunosuppressive flavones and lignans from Bupleurum scorzonerifolium

Two lignans, isochaihulactone and chaihunaphthone, together with eleven known compounds were isolated from the root of Bupleurum scorzonerifolium. Their structures were established on the basis of spectral evidence. In biological testing, eugenin and saikochromone potently inhibited CD28-costimulated activation of human peripheral blood T cells.     

Dibenzocyclooctadiene lignans from Kadsura philippinensis

Lignans with the dibenzocyclooctadiene skeleton, kadsuphilols I-L, and one C₁₉-homolignan, kadsuphilol M, were isolated by chromatographic fractionation of an ethyl acetate extract of the aerial parts of Kadsura philippinensis. Their structures were elucidated through extensive spectroscopic methods, including HRESIMS and 2D NMR experiments (HMQC, COSY and HMBC). The stereochemistry at the chiral centers and the biphenyl moist, were determined using NOESY, as well as analysis of CD spectra, respectively. The relative configuration of heteroclitin J was confirmed by single crystal X-ray crystallographic analysis. The in vitro radical-scavenging activities of these compounds by using DPPH were evaluated.     

Trypanocidal tetrahydrofuran lignans from Peperomia blanda

Five tetrahydrofuran lignans and two known flavones were isolated from the aerial parts of Peperomia blanda. The structures of the isolated lignans were elucidated by interpretation of their spectroscopic data, including by gHMQC and gHMBC. The relative and absolute configurations of the isolates were determined from NOESY interactions and optical properties, respectively. Four of the lignans were diastereomeric whilst one was of mixed biosynthetic origin. All but one of the lignans exhibited high in vitro trypanocidal activity when assayed against epimastigotes of Trypanosoma cruzi strain Y.     

Lignoids from the fruit of three Virola species

The fruits of Virola peruviana contain, besides i 1-phenyl-1-1-(2′,6′-dihydroxyphenyl)-undecan-1-one and the neolignan 2,3-dimethyl-1,4-diveratryl-n-butan-1-ol, 3,4-methylenedioxycinnamyl alcohol. In contrast, the fruits of V. flexuosa and V. multinervia both contain oxidative dimers of cinnamyl alcohols such as asarinin, cubebin, dihydrocubebin and sesamin. The former contains additionally fargesin and O-methylpiperitol, besides 7,4′-dimethoxyflavone, and the latter contains additionally hinokinin.     

1,11-diarylundecan-1-one and 4-aryltetralone neolignans from Virola sebifera

The seed of Virola sebifera contains besides the polyketide 1 - (2′,6′ - dihydroxyphenyl) - 11 - henylundecan - 1 - one, four neolignans: (2S, 3S, 4R) - 4 - hydroxy - 2,3 - dimethyl - 5,6 - methylenedioxy - 4 - piperonyl - 1 - tetralone and its 2-epimer, as well as (2R, 3R, 4S) - 4 - hydroxy - 6,7 - dimethoxy - 2,3 - dimethyl 4 - piperonyl - 1 - tetralone and its (2R, 3S, 4R) - dehydroxy analogue.     

Glycosides of arylnaphthalene lignans from Acanthus mollis having axial chirality

Glycosides of arylnaphthalene lignans having axial chirality were isolated from Acanthus mollis. Owing to the axial chirality, their structure, including absolute configuration, was determined by means of extensive spectroscopic data such as UV, IR, MS, 1D and 2D NMR spectra, and computational chiroptical methods. A compound, 2′,4-dihydroxyretrohelioxanthin (2′-hydroxy-justirumalin), has a structure containing two aromatic moieties with substituents hindering rotation about the biaryl axis. The aglycone was connected to a saccharide moiety linked at C-4 or C-2′ and made up of one or four sugars (rhamnose or quinovose, and tetrasaccharide 4-O-β-d-xylopyranosyl-(1′′′′′-6′′)-O-[β-d-rhamnopyranosyl-(1′′′′-3′′)]-O-β-d-apiofuranosyl-(1′′′′-2′′)-O-β-d-glucopyranoside and quinovose). Two mono- and one tetraglycoside gave positive results in the sea urchin eggs test (Paracentrotus lividus) of cytotoxicity and in a crown gall tumor on potato disks test (Agrobacterium tumefaciens).