Dineolignans of 3-O-4′ diphenyl ether-type from fruits of Magnolia obovata

Highlights

• Seven dineolignans of the 3-O-4′ diphenyl ether-type were isolated from Magnolia obovata fruits and named obovatalignans C-I.

• Chemical structures including stereo-chemistries were determined through extensive NMR, MS, and CD spectroscopic experiments.

• Compounds 1–5 are dilignans that include a 1,4-benzodioxane moiety, which rarely occurs in nature.

Abstract

Seven dineolignans of the 3-O-4′ diphenyl ether-type (obovatalignans C-I, respectively), were isolated from fruits of Magnolia obovata through repeated silica gel (SiO₂), octadecyl SiO₂, and Sep-Pak chromatographies. Their chemical structures were determined based on various spectroscopic methods including NMR, HR-MS, IR, specific rotation, and CD spectrometry. Especially, compounds 1–5 include the relatively rare 1,4-benzodioxane ring moiety in the molecular structure.

Introduction

The Magnoliaceae is a family of about 220 species of deciduous or evergreen trees native to Asia and America. Among the Magnolia species, Magnolia obovata and M. officinalis are very important in traditional Korean-Chinese-Japanese herbal medicine. In the Korean and Chinese Pharmacopoeia, there are two entries containing Magnolia species: Magnoliae Cortex, “Hoo-Bahk” (the dry bark of the stem of M. obovata, M. officinalis and M. officinalis var. biloba Rehd. et Wils) and the Japanese Magnoliae Cortex (dry bark of M. obovata). Magnoliae Flos, “Xinyi” (the dry flower buds of M. officinalis, M. officinalis var. biloba or M. denudata) has been also used for medicinal purposes (Chung and Shin, 2002). Indeed, the roots and flower buds of many Magnolia species have been both widely and long used in Korean and Chinese medicine for treatment of gastrointestinal maladies and phlegm (Yuan and Lin, 2000). Especially, the extracts of M. obovata or its metabolites have been extensively studied for their biological and pharmacological effects, which included cytotoxic (Kim and Ryu, 1999; Youn et al., 2008a, Youn et al., 2008b, Sawasdee et al., 2013), apotosis inducing (Ikeda and Nagase, 2002), anti-mutagenic (Saito et al., 2006), inhibition of MMP-2 (Lee et al., 2007), prevention of skin photoaging (Tanaka et al., 2007), inhibition of NO production (Matsuda et al., 2001), anti-gastric (Cho et al., 2008), neurotrophic (Fukuyama et al., 1989; Yang et al., 2013), improvement of Alzheimer's disease (Choi et al., 2012), antimicrobial (Chang et al., 1998), anti-platelet (Pyo et al., 2002), anti-emetic (Kawai et al., 1994), antioxidation (Haraguchi et al., 1997), and anticomplementary (Min, 2008) activities.

The Magnoliaceae is composed of the genera Kadsura, Liriodendron, Magnolia, Michelia, and Schisandra, among which Magnolia and Schisandra are the most widely distributed in the Far East Asia, Korea, China, and Japan (Chung and Shin, 2002). The fruits of S. chinensis, the representative medicinal plant of the genus Schisandra, are reported to contain dibenzocyclooctane type lignans and sesquiterpenoids as major components (Nakajima et al., 1983). The most widely distributed plants of the genus Magnolia are M. officinalis, M. kobus, M. grandiflora, and M. obovata (Chung and Shin, 2002). The major components of M. officinalis are reported to be a variety of biphenyl type neolignans, including magnolol and honokiol (Konoshima et al., 1991), diphenyl ether type neolignans (Shen et al., 2008), furanofuranoid type lignans (Chiba et al., 2002), monoterpene-neolignans (Konoshima et al., 1991) and dineolignans (Shih et al., 2013). Numerous furanofuranoid type lignans (Seo et al., 2008) and a monofuranoid type lignan (Li et al., 2007) have also been isolated from M. kobus. Honokiol, a neolignan (Bai et al., 2003), and magnolenin C, a monofuranoid type lignan (Rao and Wu, 1978), were reported to be the main components of M. grandiflora. From M. obovata, many biphenyl type neolignans, including magnolol and honokiol (Min, 2008), diphenyl ether type neolignans (Seo et al., 2013), neolignans attached with sesquiterpenoids (Matsuda et al., 2001), and a trilignan with a 1,4-benzodioxane ring, magnolianin (Fukuyama et al., 1993) have been isolated and identified.

Meanwhile, preliminary studies of extracts of M. obovata fruits indicated the presence of lignans with the higher molecular weight than dimers of phenylpropanoids, such as dilignans from the colorization pattern and R_f value on the TLC plate, as well as the molecular ion peaks and fragmentation patterns in the UPLC-QTOF/MS analyses. Therefore, this study was initiated to identify compounds from the fruits of M. obovata. A new sesquineolignan and a new neolignan were previously isolated from M. obovata fruits and named obovatalignans A and B (Seo et al., 2016), respectively. The continuing study gave seven new dineolignans.

Phenylpropanoids are synthesized from aromatic amino acids, such as L-phenyl alanine and L-tyrosine, which are formed via the shikimic acid pathway. E2 elimination of ammonia from L-phenylalanine or L-tyrosine occurs to form cinnamic or p-coumaric acids, respectively. These can then produce diverse monolignols, including coniferyl alcohol via hydroxylation, methylation, and reduction processes. Enzymatic dehydrogenation of a phenolic hydroxyl group by an enzyme gives the corresponding monolignol radical, which exists in a variety of resonance forms. Two units of the monolignol radicals can be coupled through an enzyme-catalyzed process to form a dimer (Wallis, 2009). Among them, the term lignan refers to dimers formed by coupling of two C₆-C₃ units through C-8 and C-8′, whereas if the two C₆-C₃ units are linked through a bond other than C-8 and C-8′, it is categorized as a neolignan. Additionally, sesquilignans and dilignans are formed from three and four C₆-C₃ units, respectively, which are rarely found in nature. This paper describes a procedure for the isolation and identification of seven new dineolignans with 3-O-4′ diphenyl ether-type neolignans.