Journal of the Mexican Chemical Society ISSN: 1870-249X [email protected] Sociedad Química de México México Song, Qi; Fischer, Nikolaus H. Biologically active lignans and neolignans from Magnolia species Journal of the Mexican Chemical Society, vol. 43, núm. 6, noviembre-diciembre, 1999, pp. 211-218 Sociedad Química de México Distrito Federal, México Available in: http://www.redalyc.org/articulo.oa?id=47543607 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative Revista de la Sociedad Química de México, Vol. 43, Núm. 6 (1999) 211-218 Revisión Biologically Active Lignans and Neolignans from Magnolia Species Qi Song and Nikolaus H. Fischer* Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA Resumen. Algunos miembros del género Magnolia (familia Magno- Abstract. Members of the genus Magnolia (family Magnoliaceae), liaceae), que tienen un amplio uso en la medicina tradicional, son which have long been used in folk medicine, are rich in lignans, ricos en lignanos, neolignanos, sus oligómeros y en estructuras híbri- neolignans, their oligomers and hybrid structures. This review covers das. Esta revisión cubre la distribución y las actividades biológicas de the distribution and biological activities of this class of natural prod- este grupo de productos naturales. Se incluyen las estructuras quími- ucts. Also, the chemical structures of lignans, neolignans, oligomeric cas de los lignanos, neolignanos, lignanos oligoméricos y lignanos lignans and biosynthetically “mixed” terpenoid lignans from 19 dif- terpenoidales biosintéticamente mixtos, y se discuten sus bioactivi- ferent Magnolia species are summarized and their bioactivities are dades. discussed. Introduction These phenylpropanoid dimers are formed biogenetically through the shikimate pathway [14]. Norlignans are defined as Various taxa of the genus Magnolia (family Magnoliaceae) a group of related natural compounds, usually found to co- have long been used in folk medicine, and have attracted con- occur with lignans or neolignans, which have a C16 to C17 core siderable interest with respect to structural determinations of structure, and they are apparently biosynthetically derived their biologically active metabolites for their potential use as from two arylpropane units by loss of one or two carbons, pharmaceuticals and/or agrochemicals. Members of this genus probably through decarboxylations. As summarized in Figs. 1 are known to be rich in a wide variety of biologically active and 2, in this review the lignans, neolignans as well as compounds including lignans, neolignans, terpenoids as well oligomeric lignans, hybrid lignans and norlignans are divided as alkaloids [1]. In many Magnolia species, lignans and into twelve subgroups (A-L) dependent upon common struc- neolignans represent the major chemical constituents. Several tural features. Group B represents substituted tetrahydrofurans reviews covering the structural aspects of lignans are available including 2,5-diaryl-3,4-dimethyltetrahydrofurans and 2,4- [2-7] and their biological activities have also been reviewed diaryl-3,5-dimethyltetrahydrofurans. Hybrid neolignans [8]. However, no comprehensive review of lignans and neolig- (group I) consist of monoterpene- and sesquiterpene-neolig- nans from the genus Magnolia is available. This summary of nans, and group J includes di- and tri-lignans. The skeletal the distribution and chemical structure of lignans and neolig- types of these twelve groups are presented in Figs. 1 and 2. nans from Magnolia also includes a discussion of their biolog- An earlier comprehensive review on the distribution of ical activities. lignans and neolignans in the plant Kingdom is available [15]. As shown in Figs. 1 and 5, lignans are defined as dimers Lignans and neolignans from the genus Magnolia are summa- of phenylpropanoid (C6-C3) units linked by the central carbons rized in Table 1, which lists compounds from 19 different b-b’ (C8-C8’) (A-D) of their side chains [9, 11]. In contrast, species. Lignans have been isolated from various parts of naturally occurring dimers that exhibit linkages other than this Magnolias: tree bark [16, 17], leaves and stems [18-20], root b-b’-type linkage are known as neolignans (Fig. 2) [12, 13]. bark [21], flower buds [22], and seeds [23]. A wide spectrum of biological activities of lignans and neolignans have been reported. This includes cytotoxic, anti-tumor, anti-leukaemia, * Corresponding author. New address: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences. School of Pharmacy, The anti-viral, anti-microbial, anti-inflammatory, anti-allergy, as University of Mississippi, University, MS 38677, USA. Fax: 662-915-7026; well as anti-fungal, insecticidal and miscellaneous physiologi- E-mail: [email protected] cal effects [5, 8]. They may also play a significantly ecological 212 Rev. Soc. Quím. Méx. Vol. 43, Núm. 6 (1999) Qi Song and Nikolaus H. Fischer role as mediators in plant-fungi, plant-plant, and plant-insect interactions [8]. At the molecular level, they interrupt the syn- thesis of DNA and the transport of nucleotides and are inhibitors of key enzymes [8, 24]. Lignans and neolignans: structure and biological activity Fig. 1. Structural Types of Lignans. Flower buds of Magnolia salicifolia Maxim. have been used in traditional Kampo and Chinese medicines, especially for Pinoresinol (18) was reported to be responsible for the piscici- nasal allergy and nasal empyema. Chloroform extracts of this dal activity of this plant [34], while syringaresinol (25) and its medicinal plant exhibited a remarkable anti-allergy activity in 4’-O-b-D-glucopyranoside (26) from in M. officinalis exhibit- passive cutaneous anaphylaxis (PCA) tests [25, 26]. Along ed remarkable cytotoxic and anti-leukaemic activities [16, 35]. with two other neolignans, magnosalin (1) (Fig. 3) was isolat- Other biological activities of this group of compounds also ed in the course of a search for biologically active principles include the germination inhibitory activity of fargesin (14) from this plant [25, 26]. However, none of the pure com- [36], enhancing toxicity of insecticides of sesamin (22) [37] pounds were active [22]. and anti-hypertensive activity of pinoresinol (18) [38]. A number of substituted tetrahydrofuran-type lignans (2- Only two compounds of the arylnaphthalene group, gua- 10) have been isolated from Magnolia species. Magnosalicin iacin (28) [45] and magnoshinin (29) [25, 26] have been iso- (7) was isolated from M. salicifolia [25, 26]. The root bark of lated from M. kachirachira and M. salicifolia, respectively, M. acuminata L., a tall native forest tree of the eastern and but no biological activity was reported. mainly southern United States, which was used in the treat- The spirocyclohexadienone denudatone (30) and futoe- ment of malaria and rheumatism in the past, afforded three none (31) are the only two spiro- (5,5)- undecanoids neolig- compounds, galgravin (2), calopiptin (3) and veraguensin (5) nans found in family Magnoliaceae [3, 6]. They were isolated [21], the latter compound also being present in M. liliflora from the aerial parts of the Japanese ornamental plants M. [20], M. denudata [21] and M. saulangiana [39]. The 2,4- denudata and M. liliflora Desr. [20, 39]. Biogenetically, the diaryl-dimethyltetrahydrofurans fargesol (6) from M. fargesii formation of denudatone (30) can be formulated as an oxida- [27], magnostellin A (8) and B (9) from M. stellata Maxim. tive coupling of propenylphenol or allylphenol derivatives fol- [28] appear to be formed by the formal cleavage of a C-O lowed by stereoselective reactions of a quinone methide inter- bond. Such cleavages might in some cases be a mode of mediate [40]. biosynthesis. Magnostellin B (9) is included here since its Benzofuranoids and hydrobenzofuranoids are well repre- structure can be formally derived from a dioxabicyclooctane sented in the genus Magnolia. In search for Ca2+ -antagonist (C, Figure 1) by C-C cleavage. The determination of the stere- activity on the taenia coli of the guinea pig from the Chinese ochemistry for these types of compounds made extensive use herb hsin-i (M. fargesii), fargesones A (47), B (48), and C of NMR studies, X-ray analysis, chemical interconversions, (49), in which a resorcinol nucleus appears as a substituted and structural comparisons with compounds of known cyclohexenone, were isolated from the flower buds of M. far- absolute configuration [29]. The 2,3-diaryl-3,7-dioxabicyclo[3.3.0]octanes-type lig- nans (Fig. 1, C) represent one of the largest groups of lignans found in the genus Magnolia (Table 1). Among seventeen compounds, aschantin (11), demethoxyaschantin (12), far- gesin (14), magnolin (16), pinoresinol dimethyl ether (19) and liroresinol-B, isolated from flower buds of M. biondii Pump., have demonstrated antagonistic activities against platelet acti- vating factor in the [3H]PAF receptor binding bioassay, which may have potential use in the treatment of inflammation, car- diovasular and pulmonary diseases [30]. Some of these com- pounds are also present in other Magnolia species (Table 1), M. stellata Maxim. [28], M. fargesii [31], M. kobus [19], M. pterocarpa [32], M. officinalis Rehd. et Wils. [33], and M. saulangiana [33]. Flower buds of M. fargesii are also