Lignan Skeleton Research Articles

Total Synthesis of (+)-Silybin A.

We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.

Design strategy and preliminary antiproliferative investigation of a modified lignan skeleton derived from aryne and statin.

The biological activities of natural products (NPs) provided precious resources for the development of new drugs. Numerous studies have shown that statins exhibit cytotoxic potential, which is now an extensive focus of investigation. Herein, a remarkably efficient method for modification of statins using hexadehydro-Diels-Alder (HDDA) arynes has been described. Notably, lactone, as the biologically active group of statins, was removed during the reaction and a novel modified lignan skeleton was generated via the Alder-ene process. Unexpectedly, these statin-derived novel chemical scaffolds exhibited moderate inhibition effects on the proliferation of cancer cells as determined by CCK-8 assays, and the IC50 values were in the micromolar range.

Oxidative Transformations of Lignans.

Numerous oxidative transformations of lignan structures have been reported in the literature. In this paper we present an overview on the current findings in the field. The focus is put on transformations targeting a specific structure, a specific reaction, or an interconversion of the lignan skeleton. Oxidative transformations related to biosynthesis, antioxidant measurements, and total syntheses are mostly excluded. Non-metal mediated as well as metal mediated oxidations are reported, and mechanisms based on hydrogen abstractions, epoxidations, hydroxylations, and radical reactions are discussed for the transformation and interconversion of lignan structures. Enzymatic oxidations, photooxidation, and electrochemical oxidations are also briefly reported.

Identification of compounds with cytotoxic activity from Millettia dorwardi Coll. Et. Hemsl

Two new lignan derivatives and nine known compounds were isolated from the EtOAc and n-BuOH extracts of Millettia dorwardi Coll. Et. Hemsl. The structures of the compounds were determined by 1D and 2D NMR, CD and HRMS. Then, cytotoxic effects of these compounds were evaluated against five cancer cell lines (HepG2, HCT116, MCF7, Raji and KG-1). Results showed the isolated compounds have no obvious cytotoxic activity, but millepurpan (5) showed moderate growth inhibitory activity against Raij and KG-1 cells, with IC50 values of 36.13 and 30.11 μM, respectively. Further activity evaluation revealed that millepurpan (5) could induce G1 arrest and apoptosis in KG-1 cells. The lignan skeleton was isolated from Millettia genus for the first time and all compounds were firstly reported from Millettia dorwardi Coll. Et.

Total syntheses of schizandriside, saracoside and (±)-isolariciresinol with antioxidant activities.

Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs-Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC50 = 34.4, 28.8, 53.0μM, respectively.

Titanocene(III) chloride mediated radical induced addition-elimination route to the synthesis of racemic and optically active trisubstituted tetrahydrofurans: Formal synthesis of magnofargesin and 7′-epimagnofargesin

Titanocene(III) Chloride mediated radical induced synthesis of 4-benzylidene substituted tetrahydrofuran, a typical lignan skeleton, has been accomplished in good yield through addition-elimination route in racemic as well as in optically active forms. The method has been applied to the synthesis of furano lignans, magnofargesin (1) and 7′-epimagnofargesin (2) in optically active forms. Titanocene(III) Chloride mediated radical induced synthesis of 4-benzylidene substituted tetrahydrofuran, a typical lignan skeleton, has been accomplished in good yield through addition-elimination route in racemic as well as in optically active forms. The method has been applied to the synthesis of furano lignans, magnofargesin and 7´-epimagnofargesin in optically active forms.

Stereocontrolled Total Syntheses of Optically Active Furofuran Lignans

Plant products (+)-sesamin, (+)-sesaminol, (+)-methylpiperitol, (+)-aschantin, and (+)-5'-hydroxymethylpiperitol were synthesized in a highly stereocontrolled manner through l -proline-catalyzed bifunctional-urea-accelerated cross-aldol reaction, followed by biomimetic construction of the furofuran lignan skeleton through a quinomethide intermediate.

ChemInform Abstract: A Coumarin Lignanoid from the Stems of Kadsura heteroclita.

AbstractCoumarinlignan (I), possessing a unique coumarin‐containing lignan skeleton shows good anti‐HBV activity against HbeAg and HbsAg, and moderate anti‐fibrotic and neuroprotective activities.

A coumarin lignanoid from the stems of Kadsura heteroclita.

Coumarinlignan (1), possessing a unique coumarin-containing lignan skeleton, was isolated from the stems of Kadsura heteroclita. Its structure and absolute configuration were determined by spectroscopic techniques, especially 2D NMR and X-ray crystallographic data analyses. The proposed biosynthetic pathway is discussed. This new compound showed good anti-HBV activity against HBeAg and HBsAg, and moderate anti-fibrotic and neuroprotective activities.

Total Syntheses of (+)-Sesamin and (+)-Sesaminol

Abstract Total syntheses of (+)-sesamin (1a) and (+)-sesaminol (1b), which are major components of sesame lignans derived from Sesamum indicum, were accomplished in a highly stereocontrolled manner. Key steps include an l-proline-catalyzed cross-aldol reaction, which was accelerated with the aid of bifunctional urea 7, and the construction of a furofuran lignan skeleton through a quinomethide intermediate.

Two novel lignans from Gaultheria yunnanensis

Two new lignans, 9-salicyl-(+)-isolariciresinol (1) and gaultheroside G (2), together with seven known compounds, were isolated from the ethanolic extract of the whole plant of Gaultheria yunnanensis. Their structures were determined by extensive NMR and MS analyses. Gaultheroside G (2) was found to have an unusual ether linkage between the 2 and 9′ positions of aryl-tetralin lignan skeleton. All nine compounds were assayed for inhibitory effects against nitric oxide and pro-inflammatory cytokines TNF-α and IL-6 release in LPS-induced RAW 246.7 macrophages, while no significant activities were observed for the evaluated compounds.

Stereocontrolled Total Synthesis of Hedyotol A

The total synthesis of hedyotol A (1), a natural product isolated from Hedyotis lawsoniae (DC.) Wight et Arn. (Rubiaceae), was accomplished in a highly stereocontrolled manner. Key steps include an L-proline-catalyzed cross-aldol reaction and the biomimetic construction of a furofuran lignan skeleton through a quinomethide intermediate.

A new tetrahydrofuran lignan diglycoside from Viola tianshanica Maxim.

A new lignan glycoside, tianshanoside A (1), together with a known phenylpropanoid glycoside, syringin (2) and two known lignan glycosides, picraquassioside C (3), and aketrilignoside B (4), were isolated from the whole plant of Viola tianshanica Maxim. The structure of the new compound was elucidated by extensive NMR (1H, 13C, COSY, HSQC, HMBC and ROESY) and high resolution mass spectrometry analysis. The three lignans 1, 3, and 4 did not exhibit significant cytotoxicity against human gastric cancer Ags cells or HepG2 liver cancer cells. This is the first report of the isolation of a lignan skeleton from the genus Viola L.

Polar secondary metabolites from Ocimum sanctum L.

The aim of this study was to investigate the polar constituents of Ocimum sanctum L. (Lamiaceae), which is used in ayurvedic medicine under the common name tulsi. In continuation to our previous studies [1 – 3], we now investigated the methanol: water (7:3) extract of its aerial parts. The extract was fractionated using RP18-MPLC, CC on Sephadex LH 20 (MeOH) and semi-prep RP18-HPLC and afforded trans-p-coumaric acid 4-O-β-D-glucopyranoside; 3-(3,4-dihydroxyphenyl)lactic acid; protocatechuic acid; (-)-rhabdosin, a caffeic acid tetramer with a lignan skeleton; the neolignan shimobashiric acid C, recently isolated from Keiskea japonica-Lamiaceae [4]; apigenin 7-O-β-D-glucuronide and luteolin 7-O-β-D-glucuronide. The structures of the isolated compounds were confirmed by spectroscopic methods, including 1D- & 2D-NMR, UV-Vis. Our results corroborate with literature concerning the flavonoid pattern. The genus Ocimum L. is divided in three subgenera: subgenus Ocimum (sections Ocimum, Gratissima and Hiantia), subgenus Nautochilus and subgenus Gymnocimum. O. sanctum L. belongs to the subgenus Gymnocimum, which is characterized by the presence of flavonoid glucuronides, totally absent in the taxa of the other two subgenera [5].

First highly stereocontrolled synthesis of the unusual 1-hydroxy endo, endo-2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignan skeleton

This Letter describes a highly diastereoselective synthesis of the unique 1-hydroxy endo, endo-2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane skeleton starting from a stereodefined 4-arylidenetetrahydrofuran obtained by a multicomponent reaction. The key step of this synthesis is a dealkylative cyclization reaction performed on the corresponding epoxide, generating four contiguous stereogenic centers with total stereocontrol.

Total Synthesis of (±)-Agastinol

A synthesis of the tetrahydrofuran lignan (±)-agastinol, starting from the cheap Vanillin, has been developed based on Stobbe reaction with diethyl succinate to give the skeleton of lignan, which was then reduced to afford meso- and threo-(±)-secoisolanciresinol. threo-(±)-Secoisolanciresinol was treated with DDQ in acetic acid to give the 2-aryl tetrahydrofuran lignan, and which was then condensed with ferulic acid to give (±)-agastinol for the first time.

Synthesis of Threo-(±)-9,9-Dibenzoylsecoisolariciresinol and its Isomer

The total synthesis of threo-(±)-9,9-dibenzoylsecoisolariciresinol and its isomer based on two Stobbe reactions as C–C bond-forming steps used a protected vanillin and diethyl; succinate to give the skeleton of lignan, followed by reduction to afford threo- and meso-(±)-secoisolariciresinol Both were treated with benzoyl chloride to obtain the natural product threo-(±)-9,9-dibenzoylsecoisolariciresinol and Its isomer meso-(±)-9,9-dibenzoylsecoisolariciresinol for the first time.

Total synthesis of (±)-divanillyltetrahydrofuran ferulate

A convenient method for the synthesis of sesquilignan threo- and erythro-(±)-divanillyltetrahydrofuran ferulate is described. The synthesis was based on a unified synthetic strategy involving two Stobbe condensations to give the skeleton of lignan, and then reduction reaction to form meso- and threo-(±)-secoisolanciresinol. meso- and threo-(±)-secoisolanciresinol were separated by flash column chromatography, followed by intramolecular reaction with TsCl to afford the key intermediate meso- or threo-(±)-shonanin, then condensation with ferulaic acid to obtain sesquilignan threo- or its analogue erythro-(±)-divanillyltetrahydrofuran ferulate.

New neuroprotective dibenzylbutane lignans isolated from Machilus thunbergii

Two new dibenzylbutane lignans, namely rel-methyl (2S)-2-hydroxy-2-2′-((2″R,3″R)-4″-guaiacyl-2″,3″dimethylbutyl)-5′-oxo-2′,5′-dihydro-2-furanylethnoate (1) and rel-methyl (2S)-2-hydroxy-2-2′-((2″R,3″S)-4″-guaiacyl-2″,3″dimethylbutyl)-5′-oxo-2′,5′-dihydro-2-furanylethnoate (2), were isolated from the bark of Machilus thunbergii. Their structures were elucidated by spectral analysis. These two lignans exerted significant neuroprotective activities against glutamate-induced neurotoxicity in primary cultures of rat cortical cells. Compounds 1 and 2 represent a new type of lignan skeleton that has not been reported so far from nature.

The total synthesis of Cannabisin G

A convenient method for the synthesis of lignanamide Cannabisin G, starting from the vanillin, was developed. The convergent synthesis was based on the Stobbe reaction as C-C bond-forming steps to give the skeleton of lignan, which was condensed with a derivative of tyramine to obtain synthetic Cannabisin G for the first time.