Lignans

Lignans consist of two phenylpropane units linked by a C—C-bond between the carbon atoms 2 and 2 of the side chain. The presence of further 0-heterocyclic rings is common (cf. the formulas for cubebin, -peltatin, podophyllotoxin, Aegilops lignan and olivil. Fig. 305). 

Lignans are formed by the reductive dimerization of cinnamic alcohols or cinnamic acids. During the formation of the C—C-bond between the C-atoms 2 and 2 two new centres of asymmetry are formed. The additional rings present in several lignans are built after the dimerization. 

Lignans are polyphenols which belong to the group of phytoestrogens (cf. 16.2.9). Four compounds (I-IV in Formula 18.33) will be presented here. Pinoresinol (I) is a dimer of coniferyl alcohol. Lignans widely occur in low concentrations in food (examples in Table 18.29), linseed and sesame being especially rich. 

7 Lignans.- Feeding experiments and degradation studies have established the specific incorporation of two phenylpropane units from phenylalanine and p-coumaric acid into the tumour- 

0-Methyltransferases from Thuja species were able to 

Two lignans having unusual meta hydroxylated aromatic 

Interest in lignans and neolignans has risen sharply in the last few years. This is due chiefly to their powerful, varied biological activities (Table 7.3.1) exemplified by three of the most noteworthy representatives. First, the lignan podophyllotoxin (1), in the form of several semisynthetic derivatives, is one of the very few natural products from higher plants used clinically in cancer chemotherapy (30). Next kadsurenone (2), also isolated from an angiosperm species has been described as 

Chromosome damagers Inhibitors of nucleoside uptake Nucleic acids 

Inhibitors of cAMP phosphodiesterase Inhibitors of fungal enzymes Inhibitors of mitochondrial respiration Inhibitors of oxidases Enzymes 

Antimitotics Cytotoxic agents Tubulin binders Cells 

Antifeedants Inhibitors of larval growth Juvenile hormones Synergists of insecticides Insects 

The term lignan typically refers to dimers of monolignols that are linked via an 8-8 (P-P ) bond, whereas the term neolignan refers to dimers and oligomers that contain bonds other than the 8-8 bond. Most lignans are optically active, and typically only one enantiomer is found in a given species. Examples of lignans include (+)-pinoresinol (1.72), (+)-sesamin (1.73), and (-)-plicatic acid (1.74). 

The stereo-selective formation of certain lignans has been shown to be mediated by dirigent proteins. These proteins hold the monolignols in a specific orientation, but have no catalytic activity (Davin et al., 1997 see also Chapter 3). 

An equimolar mixture of 3,4,5-trimethoxy phenyl iodide 157, lithium propargyl alkoxide 158, and diethyl ethoxymethylene malonate 159 was stirred at room temperature in the presence of a palladium catalyst. Then, to the resulting intermediate 161 potassium t-butoxide was added, and the ensuing base-promoted decarboxylative aromatization afforded tetrahydrofuran MCR adduct 162 in good yield. The ester was first reduced and the furan ring was hydrogenated with Raney nickel to furnish a diastereomeric mixture of products 163 in high yield. Further synthetic manipulations then provided a known precursor to the natural product. 

Chappie (2002), Boerjan et al. (2003), Rogers and Campbell (2004), Davin and Lewis (2005b) and Chiang (2006). 

R1 = H R2 = H 4-Coumaroyl-CoA 4-Cou mar-aldehyde 4-Coumaryl alcohol 4-Coumaryl alcohol 4-O-p-glucoside 

R1 =H R2 = OCRs Feruloyl-CoA Coniferaldehyde Coniferyl alcohol Coniferyl alcohol 4-O-p-glucoside (Coniferin) 

R1 = OCRs R2 = OCRs Sinapoyl-CoA Sinapaldehyde Sinapyl alcohol Sinapyl alcohol 4-O-p-glucoside (Syringin) 

Reviews that include aspects of monolignol biosynthesis have been published by, e.g., Lewis and Yamamoto (1990), Davin and Lewis (1992), Whetten and Sederoff (1995), Boudet (1998), Van Rensburg et al. (2000), Dixon et al. (2001), Anterola and Lewis (2002), Boerjan et al. (2003) and Davin and Lewis (2003), Dixon and Reddy (2003), Goujon et al. (2003b), Chiang (2006). 

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RESEARCH OF LIGNANS AND ESSENTIAL OILS FROM THE ROOT ARCTIUM LAPPA L. 

Lignans show strong antitumor, antiviral and antibacterial activity, as well as influence upon expression of the tumor necrosis factor-alpha. 

Separation of chloroformic fraction of raw material by a polyamide sorbent with the following individual fractions elution and crystallization allowed to study lignans of burdock with IR-, mass- and NMR spectroscopy. In result, aixtiin, arctigenin, lappaols were identified. Sepai ation of essential oils was provided by the method two of State Phaiiuacopeias of the Ukraine. Essential oils were analyzed by the means of gas chromatography. 

Heterolignans, synthetic analogs of lignans containing heterocylic fragments 99H(51)1443. 

Bioactive polyphenol acids and lignans with 0-heterocyclic fragments and terpenoid 8-lactones as components of traditional Chinese drugs 98PAC547. 

The structure of carpanone (1) was revealed by Australian scientists in 1969.1 Carpanone, a hexacyclic molecule and host of five contiguous stereogenic centers, is a lignan found in the bark of the car-pano tree. 

Lawesson s reagent 475 f., 738, 742, 746, 752 Lederle 562 lepicidin aglycon 595 f. ligand-accelerated catalysis 681 f. lignane 95... 

The most useful of the insertion processes is the intramolecular reactions that occur with high selectivity for the formation of five-membered ring products. The electrophilic nature of the process is suggested by C-H bond reactivity in competitive experiments (3°>20 >1°) [76, 77]. Asymmetric catalysis with Rh2(MPPIM)4 has been used to prepare a wide variety of lignans that include (-)-enterolactone (3) [8], as well as (R)-(-)-baclofen (2) [7],2-deoxyxylolactone (31) [80,81],and (S)-(+)-imperanane (32) [82].Enantioselectivities are 91-96%... 

Podophyllotoxin, a plant lignan, is a potent antimitotic agent (Figure 6.61). An enantioselective synthesis of (—)-podophyllotoxin was achieved via the enzymatic desymmetrization of an advanced meso-diacetate, through PPL-mediated diester hydrolysis [157]. 

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