Abstract
Lignans are phenylpropanoid dimers, where the phenylpropane units are linked by the central carbon (C8) of their side chains. Ligans vary substantially in oxidation level, substitution pattern, and the chemical structure of their basic carbon framework. In addition to structural diversity, lignans show considerable diversity in terms of enantiomeric composition, biosynthesis, and phylogenetic distribution. In this review, these diversities are outlined and the phylogenetic distribution of plants producing 66 typical lignans is listed. The distribution is correlated with the putative biosynthetic pathways of the lignans and discussed from evolutionary aspects.
Abbreviations: SIRD – Secoisolariciresinol dehydrogenase; PLR – pinoresinol lariciresinol reductase; DP – dirigent protein
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Agata I, Hatano T, Nishibe S & Okuda T (1988) Rabdosiin, a new rosmarinic acid dimer with a lignan skeleton, from Rabdosia japonica. Chem. Pharm. Bull. 36: 3223–3225.
Ayres DC & Loike JD (1990) Lignans Chemical, Biological and Clinical Properties. Cambridge University Press, Cambridge.
Barrero AF, Haïdour A & Dorado MM (1994) Lignans from the wood of Abies pinsapo. J. Nat. Prod. 57: 713–719.
Broomhead AJ, Rahman MMA, Dewick PM, Jackson DE & Lu-cas JA (1991) Matairesinol as precursor of Podophyllum lignans. Phytochemistry 30: 1489-1492.
Charlton JL & Chee G-L (1997) Asymmetric synthesis of lignans using oxazolidinones as chiral auxiliaries. Can. J. Chem. 75: 1076–1083.
Chen Y-g, Sun H-d, Xu Z-h & Qin G-w (2001) Studies on chemical constituents of Stellera chamejasma L. China J. Chin. Materia Medica 26: 477–479.
Chu A, Dinkova A, Davin LB, Bedgar DL & Lewis NG (1993) Ste-reospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia. J. Biol. Chem. 268: 27026–27033.
Cronquist A (1981) An integrated system of classification of flowering plants. Columbia University Press, New York.
Cullmann F, Adam K-P & Becker H (1993) Bisbibenzyls and lignans from Pellia epiphylla. Phytochemistry 34: 831–834.
Cullmann F, Adam K-P, Zapp J & Becker H (1996) Pelliatin, a mac-rocyclic lignan derivative from Pellia epiphylla. Phytochemistry 41: 611–615.
Cullmann F, Schmidt A, Schuld F, Trennheuser ML & Becher H (1999a) Lignans from the liverworts Lepidozia incurvata, Chiloscyphus polyanthos and Jungermannia exsertifolia ssp. cordifolia. Phytochemistry 52: 1647–1650.
Cullmann F & Becker H (1999b) Lignans from the liverwort Lepicolea ochroleuca. Phytochemistry 52: 1651–1656.
Davin LB, Wang H-B, Crowell AL, Bedgar DL, Martin DM, Sarkanen S & Lewis NG (1997) Stereoselective bimolecular phenoxy radical coupling by an auxiliary (dirigent) protein without an active center. Science 275: 362–366.
Della Greca M, Molinaro A, Monaco P & Previtera L (1993) Two new lignan glucosides from Arum italicum. Heterocycles 36: 2081–2086.
Dewick PM (1989) Biosynthesis of lignans. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, Vol. 5 Structure elucidation (Part B) (pp. 459–503). Elsevier, Amsterdam.
Dinkova-Kostova AT, Gang DR, Davin LB, Bedgar DL, Chu A & Lewis NG (1996) (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia. J. Biol. Chem. 271: 29473–29482.
Erickson M & Miksche GE (1974) On the occurrence of lignin or polyphenols in some mosses and liverworts. Phytochemistry 13: 2295–2299.
Erdtman H (1933) Dehydrierungen in der Coniferylreihe. (I). Dehydrodieugenol und Dehydrodiisoeugenol. Biochem. Z. 258: 172–180.
Fonseca SF, de Paiva Campello J, Barata LES & Rúveda EA (1978) 13 C NMR spectral analysis of lignans from Araucaria angustifolia. Phytochemistry 17: 499–502.
Fujita M, Gang DR, Davin LB & Lewis NG (1999) Recombin-ant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274: 618–627.
Furuki T & Mizutani M(1994) Checklist of Japanese Hepaticae and Anthocerotae, 1993. Proc. Bryol. Soc. Japan 6: 75–83.
Gibbs RD (1974) Chemotaxonomy of flowering plants, Vol 1. Constituents. McGill-Queen's University Press, Montreal.
Gottlieb OR (1972) Chemosystematics of the Lauraceae. Phytochemistry 11: 1537–1570.
Gottlieb OR (1978) Neolignans. Fortschr. Chem. Org. Naturst. 35: 1–72.
Haworth RD (1936) Natural resins. Ann. Rep. Prog. Chem. 33: 266–279.
Hostettler FD & Seikel MK (1969) Lignans of Ulmus thomasii heartwood-II. Lignans related to thomasic acid. Tetrahedron 25: 2325–2337.
Ishii H, Ishikawa T, Mihara M & Akaike M (1983) Studies on the chemical constituents of Rutaceous plants. XLVIII. The chemical constituents of Xanthoxylum ailanthoides Sieb. et Zucc. [Fagara ailanthoides (Sieb. et Zucc.) Engl.]. (3) Isolation of the chemical constituents of the bark. Yakugaku Zasshi 103: 279–292.
Jackson DE & Dewick PM (1984a) Biosynthesis of Podophyllum lignans-I. Cinnamic acid precursors of podophyllotoxin in Podophyllum hexandrum. Phytochemistry 23: 1029–1035.
Jackson DE & Dewick PM (1984b) Biosynthesis of Podophyllum lignans-II. Interconversions of aryltetralin lignans in Podophyl-lum hexandrum. Phytochemistry 23: 1037–1042.
Jiao Y, Davin LB & Lewis NG (1998) Furanofuran lignan meta-bolism as a function of seed maturation in Sesamum indicum: Methylenedioxy bridge formation. Phytochemistry 49: 387–394.
Jiang Z-H, Tanaka T & Kouno I (1996) Chilianthins A-F, six triter-pene esters having dimeric structures from Rhoiptelea chiliantha Diels et Hand.-Mazz. Chem. Pharm. Bull. 44: 1669–1675.
Kamil WM & Dewick PM (1986a) Biosynthesis of the lignans á-and â-peltatin. Phytochemistry 25: 2089–2092.
Kamil WM & Dewick PM (1986b) Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry 25: 2093–2102.
Katayama T, Davin LB & Lewis NG (1992) An extraordinary accumulation of (-)-pinoresinol in cell-free extracts of For-sythia intermedia: evidence for enantiospecific reduction of (+)-pinoresinol. Phytochemistry 31: 3875–3881
Katayama T, Davin LB, Chu A & Lewis NG (1993) Novel benzylic ether reductions in lignan biogenesis in Forsythia intermedia. Phytochemistry 33: 581–591.
Katayama T, Masaoka T & Yamada H (1997) Biosynthesis and stereochemistry of lignans in Zanthoxylum ailanthoides I. (+)-Lariciresinol formation by enzymatic reduction of ( ±)-pinoresinols. Mokuzai Gakkaishi 43: 580–588.
Kato M (1997) Diversity and evolution of land plants. Shokabo, Tokyo.
Kato MJ, Chu A, Davin LB & Lewis NG (1998) Biosynthesis of antioxidant lignans in Sesamum indicum seeds. Phytochemistry 47: 583–591.
Kawai S, Sugishita K & Ohashi H (1999) Identification of Thuja occidentalis lignans and its biosynthetic relationship. Phytochemistry 51: 243–247.
Khamlach K, Dhal R & Brown E (1989) Total syntheses of (-)-trachelogenin, (-)-nortrachelogenin and (+)-wikstromol. Tetrahedron Lett. 30: 2221–2224.
Kitagawa S, Nishibe S, Benecke R & Thieme H (1988) Phenolic compounds from For s yt hi a leaves. II. Chem. Pharm. Bull. 36: 3667–3670.
Kobayashi W, Miyase T, Suzuki S, Noguchi H & Chen X-M (2000) Oligosaccharide esters from the roots of Polygala arillata. J. Nat. Prod. 63: 1066–1069.
Kramer KU & Green PS (1990) The families and genera of vascular plants, Vol 1, Pteridophytes & Gymnosperms. Springer-Verlag, Berlin.
Kuhlmann S, Kranz K, Lücking B, Alfermann AW & Petersen M (2002) Aspects of cytotoxic lignan biosynthesis in suspension cultures of Linum nodiflorum. Phytochemistry Rev. 1: 37–43.
Lewis NG & Davin LB (1999) Lignans: Biosynthesis and function. In: Sankawa U (ed) Comprehensive Natural Products Chemistry, Vol 1 (pp. 639-712). Elsevier, Amsterdam.
Lin L-Z, Hu S-F, Chai H-B, Pengsuparp T, Pezzuto JM, Cordell GA & Ruangrungsi N (1995) Lycorine alkaloids from Hymenocallis littoralis. Phytochemistry 40: 1295–1298.
Lin RC, Skaltsounis A-L, Seguin E, Tillequin F & Koch M (1994) Phenolic constituents of Selaginella doederleinii. Planta Med. 60: 168–170.
McCredie RS, Ritchie E & Taylor WC (1969) Constituents of Eupo-matia species. The structure and synthesis of eupomatene, a lignan of novel type from Eupomatia laurina R. Br. Aust. J. Chem. 22: 1011–1032.
MacRae WD & Towers GHN (1984) Biological activities of lignans. Phytochemistry 23: 1207–1220.
Martini U, Zapp J & Becker H (1998) Lignans from the liverwort Bazzania trilobata. Phytochemistry 49: 1139–1146.
Mikame K, Sakakibara N, Umezawa T & Shimada M (2002) Lignans of Linum flavum var. compactum. J. Wood Sci. 48: 440–445.
Miksche GE & Yasuda S (1978) Lignin of 'giant' mosses and some related species. Phytochemistry 17: 503–504.
Miyauchi T & Ozawa S (1998) Formation of (+)-eudesmin in Magnolia kobus DC. var. borealis SARG. Phytochemistry 47: 665–670.
Moinuddin SGA, Hishiyama S, Cho M-H, Davin LB & Lewis NG (2003) Synthesis and chiral HPLC analysis of the dibenzyl-tetrahydrofuran lignans, larreatricins, 8 -epi-larreatricins, 3,3-didemethoxyverrucosins and meso-3,3-didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence for regio-specific control of coupling. Org. Biomol. Chem. 1: 2307–2313.
Molog GA, Empt U, Kuhlmann S, van Uden W, Pras N, Alfermann AW & Petersen M(2001) Deoxypodophyllotoxin 6-hydroxylase, a cytochrome P450 monooxygenase from cell cultures of Linum flavum involved in the biosynthesis of cytotoxic lignans. Planta 214: 288–294.
Moss GP (2000) Nomenclature of lignans and neolignans (IUPAC Recommendations 2000). Pure Appl. Chem. 72: 1493–1523.
Nabeta K, Nakahara K, Yonekubo J, Okuyama H & Sasaya T (1991) Lignan biosynthesis in Larix leptolepis callus. Phytochemistry 30: 3591–3593.
Nishibe S, Sakushima A, Kitagawa S, Klimek B, Benecke R & Thieme H (1988) Phenolic compounds from For s yt hi a leaves (III). On the comparison of constituents between hybrid and parents. Shoyakugaku Zasshi 42: 324–328.
Okunishi T, Umezawa T & Shimada M (2000) Enantiomeric com-positions and biosynthesis of Wikstroemia sikokiana lignans. J. Wood Sci. 46: 234–242.
Okunishi T, Umezawa T & Shimada M (2001) Isolation and en-zymatic formation of lignans of Daphne genkwa and Daphne odora. J. Wood Sci. 47: 383–388.
Okunishi T, Sakakibara N, Suzuki S, Umezawa T & Shimada M (2004) Stereochemistry of matairesinol formation by Daphne secoisolariciresinol dehydrogenase. J. Wood Sci. 50: 77–81.
Ozawa S, Davin LB & Lewis NG (1993) Formation of (-)-arctigenin in Forsythia intermedia. Phytochemistry 32: 643–652.
Petersen M & Alfermann AW (2001) The production of cytotoxic lignans by plant cell cultures. Appl. Microbol. Biotechnol. 55: 135–142.
Rahman MMA, Dewick PM, Jackson DE & Lucas JA (1990) Lig-nans of Forsythia intermedia. Phytochemistry 29: 1971–1980.
Sakakibara I, Ikeya Y, Hayashi K & Mitsuhashi H (1992) Three phenyldihydronaphthalene lignanamides from fruits of Cannabis sativa. Phytochemistry 31: 3219–3223.
Sakakibara N, Suzuki S, Umezawa T & Shimada M (2003) Biosyn-thesis of yatein in Anthriscus sylvestris. Org. Biomol. Chem. 1: 2474–2485.
Scher JM, Zapp J & Becker H (2003) Lignan derivatives from the liverwort Bazzania trilobata. Phytochemistry 62: 769–777.
Suzuki H, Lee K-H, Haruna M, Iida T, Ito K & Huang H-C (1982) (+)-Arctigenin, a lignan from Wikstroemia indica. Phytochemistry 21: 1824–1825.
Suzuki S, Umezawa T & Shimada M (1998) Stereochemical difference in secoisolariciresinol formation between cell-free extracts from petioles and from ripening seeds of Arctium lappa L. Biosci. Biotech. Biochem. 62: 1468–1470.
Suzuki S, Umezawa T & Shimada M (2001) Norlignan biosynthesis in Asparagus officinalis. J. Chem. Soc. Perkin Trans. 1 3252–3257.
Suzuki S, Nakatsubo T, Umezawa T & Shimada M (2002a) First in vitro norlignan formation with Asparagus officinalis enzyme preparation. Chem. Commun. 1088–1089.
Suzuki S, Umezawa T & Shimada M (2002b) Stereochemical diversity in lignan biosynthesis of Arctium lappa L. Biosci. Biotech. Biochem. 66: 1262–1269.
Suzuki S, Sakakibara N, Umezawa T & Shimada M (2002c) Survey and enzymatic formation of lignans of Anthriscus sylvestris. J. Wood Sci. 48: 536–541.
Takaku N, Choi D-H, Mikame K, Okunishi T, Suzuki S, Ohashi H, Umezawa T & Shimada M (2001) Lignans of Chamaecyparis obtusa. J. Wood Sci. 47: 476–482.
Tandon S & Rastogi RP (1976) Wikstromol, a new lignan from Wikstroemia viridiflora. Phytochemistry 15: 1789–1791.
Tazaki H (2000) Biosynthetic studies on secondary metabolites of in vitro cultured liverworts. Nippon Nogeikagaku Kaishi 74: 137–143.
Tazaki H, Hayashida T, Ishikawa F, Taguchi D, Takasawa T & Na-beta K (1999) Lignan biosynthesis in liverworts Jamesoniella. autumnalis and Lophocolea heterophylla. Tetrahedron Lett. 40: 101–104.
Tazaki H, Ito M, Miyoshi M, Kawabata J, Fukushi E, Fujita T, Mo-touri M, Furuki T & Nabeta K (2002) Subulatin, an antioxidic caffeic acid derivative isolated from the in vitro cultured liver-worts, Jungermannia subulata, Lophocolea heterophylla,and Scapania parvitexta. Biosci. Biotechnol. Biochem. 66: 255–261.
Tiwari AK, Srinivas PV, Kumar SP & Rao JM (2001) Free radical scavenging active components from Cedrus deodara. J. Agric. Food Chem. 49: 4642–4645.
Umezawa T (1996) Biological activity and biosynthesis of lignans. Mokuzai Gakkaishi 42: 911–920.
Umezawa T (1997) Lignans. In: Higuchi T (ed) Springer Series in Wood Science, Biochemistry and Molecular Biology of Wood (pp. 181–194). Springer-Verlag, Berlin.
Umezawa T (2000) Chemistry of extractives. In Hon DN-S & Shiraishi N (eds) Wood and Cellulosic Chemistry 2nd Ed. revised and expanded (pp. 213–241). Marcel Dekker, New York.
Umezawa T (2001) Biosynthesis of lignans and related phenylpro-panoid compounds. Regulation of Plant Growth & Development 36: 57–67.
Umezawa T (2003) Phylogenetic distribution of lignan producing plants. Wood Research 90: 27–110.
Umezawa T, Davin LB & Lewis NG (1990a) Formation of the lig-nan, (-) secoisolariciresinol, by cell free extracts of For s yt hi a intermedia. Biochem. Biophys. Res. Commun. 171: 1008–1014.
Umezawa T, Davin LB, Yamamoto E, Kingston DGI & Lewis NG (1990b) Lignan biosynthesis in Forsythia species. J. Chem. Soc. Chem. Commun.: 1405–1408.
Umezawa T, Davin LB & Lewis NG (1991) Formation of lig-nans (-)-secoisolariciresinol and (-)-matairesinol with For s yt hi a intermedia cell-free extracts. J. Biol. Chem. 266: 10210–10217.
Umezawa T, Isohata T, Kuroda H, Higuchi T & Shimada M (1992) Chiral HPLC and LC-MS analysis of several lignans. In: Kuwa-hara M, Shimada M (eds) Biotechnology in Pulp and Paper Industry (pp. 507–512). Uni Publ., Tokyo.
Umezawa T, Kuroda H, Isohata T, Higuchi T & Shimada M (1994) Enantioselective lignan synthesis by cell-free extracts of Forsythia koreana. Biosci. Biotech. Biochem. 58: 230–234.
Umezawa T & Shimada M (1996a) Enantiomeric composition of (-)-pinoresinol, (+)-matairesinol and (+)-wikstromol isolated from Wikstroemia sikokiana. Mokuzai Gakkaishi 42: 180–185.
Umezawa T & Shimada M (1996b) Formation of the lignan (+)-secoisolariciresinol by cell-free extracts of Arctium lappa. Biosci. Biotech. Biochem. 60: 736–737.
Umezawa T, Okunishi T & Shimada M (1997a) Stereochemical diversity in lignan biosynthesis. Wood Research 84: 62–75.
Umezawa T, Okunishi T & Shimada M (1997b) Mechanisms of lignan biosynthesis. Annual Rep. Interdiscipl. Res. Inst. Environ. Sci. 16: 65–71.
Umezawa T, Okunishi T, Mikame K, Suzuki S, Liswidowati, Wasrin Syafii & Shimada M (1998) Mechanisms of lignan biosynthesis, part II. Annual Rep. Interdiscipl. Res. Inst. Environ. Sci. 17: 29–36.
Whiting DA (1985) Lignans and neolignans. Nat. Prod. Rep. 2: 191–211.
Xia Z-Q, Costa MA, Proctor J, Davin LB & Lewis NG (2000) Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum. Phytochemistry 55: 537–549.
Xia Z-Q, Costa MA, Pélissier HC, Davin LB & Lewis NG (2001) Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. J. Biol. Chem. 276: 12614–12623.
Yamamoto H, Inoue K & Yazaki K (2000) Caffeic acid oligomers in Lithospermum erythrorhizon cell suspension cultures. Phyto-chemistry 53: 651–657.
Zhang H-J, Tamez PA, Hoang VD, Tan GT, Hung NV, Xuan LT, Huong LM, Cuong NM, Thao DT, Soejarto DD, Fong HHS & Pezzuto JM (2001) Antimalarial compounds from Rhaphido-phora decursiva. J. Nat. Prod. 64: 772–777.
Zinsmeister HD, Becker H & Eicher T (1991) Bryophytes, a source of biologically active, naturally occurring material? Angew. Chem. Int. Ed. Engl. 30: 130–147.
Xu Z-h, Qin G-w, Li X-y & Xu R-s (2001) New biflavanones and bioactive compounds from Stellera chamaejasme L. Acta Pharmac. Sin. 36: 668–671.
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Umezawa, T. Diversity in lignan biosynthesis. Phytochemistry Reviews 2, 371–390 (2003). https://doi.org/10.1023/B:PHYT.0000045487.02836.32
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DOI: https://doi.org/10.1023/B:PHYT.0000045487.02836.32