Neglschisandrins A-B: Two New Dibenzocyclooctene Lignans from Schisandra neglecta

Two new dibenzocyclooctene lignans, neglschisandrins A-B (1-2), were isolated from the stems of Schisandra neglecta. Their structures and stereochemistries were elucidated by spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS techniques.


Introduction
The stems or fruits of plants in the Schisandraceae family are widely used in China as tonic and astringent drugs for the treatment of rheumatic arthritis, traumatic injuries and related diseases [1]. Plants of the Schisandraceae are rich in lignans, especially dibenzocyclooctene lignans, which have been found to possess some beneficial effects such as anti-HIV effect, antitumor-promoting effect, calcium antagonism effect, and anti-lipid peroxidation effect, etc. [2][3][4][5][6]. In our previous studies, some new dibenzocyclooctene lignans from the Schisandraceae family were reported [7][8][9]. To search for new biological active natural products, another Schisandraceae plant, Schisandra neglecta, was investigated. Out examination of fractions extracted from the stems of S. neglecta with Et 2 O led to the isolation and identification of two new lignans, neglschisandrins A-B (1)(2). This paper deals with the isolation and characterization of these new compounds.

Results and Discussion
Repeated column chromatography of the Et 2 O extract of the stem of S. neglecta yielded two new lignans, neglschisandrins A-B (1-2, Figure 1).  [12], 1 has no substitution at C-6 and C-9. Based on the HMQC spectrum, the protons at δ H 2.33 and 2.06 were attached to the same carbon (δ C 35.5). Similarly, the protons at δ H 2.56 and 2.64 were attached to the same carbon at δ C 39.2. Furthermore, HMBC correlations of δ H 2.06 with δ C 21.6 (C-17) and δ C 40.5 (C-7) and of δ H 2.56 with δ C 12.9 (C-18) and δ C 33.8 (C-8) indicated that δ H 2.33 and 2.06 were H 2 -6 and that δ H 2.56 and 2.64 were H 2 -9 ( Figure 2).  [13].
The 1 H-NMR spectrum of 2 also showed signals due to two aromatic protons (δ H 6.60, 6.73, each 1H, s) on two aromatic rings. Their corresponding carbon signals were assigned as δ C 107.2 and 112.8, respectively, by HMQC techniques. The chemical shifts of the protons and carbons indicated that they are located in H-4/11 and C-4/11 similar to the authentic sample [2]. HMBC correlations of δ H 6.73 with δ C 37.8 (C-9) suggested this proton was H-11. Therefore the another proton (δ H 6.60) should be H-4, which was confirmed by the HMBC correlations of δ H 6.60 with 36.9 (C-6).
Five methoxy groups (δ H 3.56, 3.81, 3.86, 3.92 and 3.85, each 3H, s) on two aromatic rings were also observed from the 1 H-NMR spectrum. An angeloyl group was observed in 1 (Figure 4), revealed the formation of an exocyclic double bond between C-7 and C-17, similar to that of the authentic sample of schisandrene reported in the literature [17].
The CD spectrum of 2 had a negative Cotton effect at 211 nm and a positive Cotton effect at 247 nm indicating that 2 has a R-biphenyl configuration. The NOESY correlations of H-4 with H-6β, H-4 with CH 2 -17, H-9α with CH 3 -18, and H-9α with H-11 in 2 suggested a twist-boat-chair (TBC) conformation for the cyclooctadiene ring ( Figure 5). The substituent positions and stereochemical assignments in the cyclooctadiene ring of 2 were supported by other NOESY correlations of H-4/MeO-3, H-8/ CH 2 -17, H-6β/CH 2 -17, and H-11/CH 3 -18. Thus, the structure of 2 was determined as that shown in Figure 1.