Alkaloids from the stem barks of Erythrina stricta

Phytochemistry 170 (2020) 112220

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Alkaloids from the stem barks of Erythrina stricta Fengqiu Li, Dewen Bi, Xuesong Liang, Ruilong Luo, Hongdan Zhuang, Liqin Wang

∗

T

Faculty of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650050, PR China

A R T I C LE I N FO

A B S T R A C T

Keywords: Erythrina stricta Roxb. (Leguminosae) Erythrinan alkaloid Pyrrolo[2,1-a]isoquinoline

Four previously undescribed erythrinan alkaloids, 8α-acetonylerythristemine, 8α-acetonylerysotrine, 10β-hydroxy-11β-methoxyerysotramidine and 3-epierysotrine, one undescribed pyrrolidine derivative, S-1-(4-hydroxy3-methoxyphenethyl)-5-hydroxy pyrrolidin-2-one, and one undescribed amide, N-(3-hydroxy-4-methoxyphenethyl)-4-hydroxylbutanamide, along with thirteen known alkaloids were isolated from the stem barks of Erythrina strica Roxb. (Leguminosae). Their structures were identified by extensive analysis of physical, spectroscopic and spectrometric data. It's very interesting that the coexistence of 3-methoxytyramine, erythrinarbine, S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxy pyrrolidin-2-one and N-(3-hydroxy-4-methoxyphenethyl)-4hydroxylbutanamide that may be closely related in biosynthesis, supports the hypothetical biogenetic pathway of pyrrolo [2,1-a]isoquinoline alkaloids.

1. Introduction Erythrina plants, botanical family Leguminosae, are the main sources for the tetracyclic erythrinan alkaloids and pterocarpans (Parsons and Palframan, 2010; Zhang et al., 2014; Selvam et al., 2017; Fahmy et al., 2018). The erythrinan alkaloids and pterocarpans have attracted interest because of their various structures, their broad range of useful biological activities, and their narrow distributions in plants (Parsons and Palframan, 2010; Zhang et al., 2014; Selvam et al., 2017; Fahmy et al., 2018). Up to now, the Erythrina genus is notably the only plant resource contains both types of the foregoing components at the same time. Genus Erythrina comprises over 130 species that are widely distributed in the tropical and subtropical areas of the world. There are ten Erythrina species distributed or cultivated in Yunnan province of China, which provides resources for systematic study on new structures and bioactivities of erythrinan alkaloids and pterocarpans. In China, Erythrina strica Roxb. (Leguminosae) is distributed in south of Yunnan and Guangxi, and east of Xizhang (Lee, 1995). The stem barks of E. strica have been used for rheumatism by the local people in Baoshan district of Yunnan province of China. Some erythrinan alkaloids, and some antibacterial and/or antioxidant phenolic compounds have been reported from E. strica (Akter et al., 2016; Wu et al., 2018). Herein, the isolation and structural determination of nineteen alkaloids are described. Through various modern isolation and structure identification technology, four previously undescribed erythrinan alkaloids, 8α-acetonyl erythristemine (1), 8α-acetonylerysotrine (2), 10β-hydroxy-11β-

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methoxyerysotramidine (3) and 3-epierysotrine (15), one undescribed pyrrolidine derivative, S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxypyrrolidin-2-one (18), and one undescribed amide, N-(3-hydroxy-4methoxyphenethyl)-4-hydroxylbutanamide (19), along with thirteen known alkaloids, (+)-11β-methoxyerysotramidine (4) (Juma and Majinda, 2004), erysotramidine (5) (Chawla et al., 1983), (+)-8-oxoerythrinine (6) (Amer et al., 1991), (+)-8-oxo-erythraline (7) (Chawla et al., 1983), (+)-erythrabine (8) (Amer et al., 1991), (+)-11-methoxyerythraline (9) (Amer et al., 1991), (+)-erythraline (10) (Amer et al., 1991), (+)-erythristemine (11) (Juma and Majinda, 2004), (+)-11β-methoxyerysodine (12) (Amer et al., 1991), (+)-erysotrine (13) (Amer et al., 1991), (+)-erysodine (14) (Wandji et al., 1995), 3methoxytyramine (16) (Cui et al., 2017), and erythrinarbine (17) (Yu et al., 1999) (Fig. 1) were obtained from the stem barks of E. strica distributed in Yunnan province. The cytotoxicity against human cancer cell lines and acetylcholinesterase inhibition of five alkaloids were evaluated. 2. Results and discussion 2.1. Structure elucidations of isolates 1–3, 15, 18 and 19 8α-Acetonylerythristemine (1) was obtained as a yellow amorphous solid. The molecular formula was assigned as C23H29NO5 based on its HRESIMS (m/z 400.2133 [M+H]+), with 10 indices of hydrogen deficiency. The 1H-NMR spectrum (Table 1) of 1 showed two aromatic singlet protons (δH 6.90 and 6.83), three olefinic protons (δH 6.56, 6.03

Corresponding author. E-mail address: [email protected] (L. Wang).

https://doi.org/10.1016/j.phytochem.2019.112220 Received 19 April 2019; Received in revised form 25 June 2019; Accepted 22 November 2019 0031-9422/ © 2019 Elsevier Ltd. All rights reserved.

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Fig. 1. The structures of compounds 1–19. Table 1 1 H NMR (500 MHz) and position

13

C NMR (125 MHz) assignments of compounds 1–3 (1 in CDCl3, 2 and 3 in CD3OD, ppm, J in Hz in parentheses).

1

2

3

δC, type

δH (J in Hz)

δC, type

δH (J in Hz)

δC, type

δH (J in Hz)

1 2 3 4

125.4 CH 131.9 CH 76.1 CH 41.4 CH2

6.56 6.03 4.02 1.80 2.43

126.2 CH 133.1 CH 77.8 CH 42.8 CH2

6.59 6.04 3.98 1.76 2.49

123.3 CH 138.1 CH 74.8 CH 41.3 CH2

7.02 6.48 3.81 1.78 2.96

5 6 7 8 10

67.6 C 141.2 C 126.7 CH 64.9 CH 44.2 CH2

11 12 13 14 15 16 17 15-OCH3 16-OCH3 3-OCH3 11-OCH3 CH2CO

73.8 CH 126.9 C 130.6 C 108.5 CH 148.0 C 148.5 C 110.8 CH 55.80 CH3 55.84 CH3 56.0 CH3 57.6 CH3 47.0 CH2

COCH3 CH2CO

30.8 CH3 208.0 C

5.63 4.46 3.39 3.16 4.16

(dd, 2.2, 10.1) (d, 10.1) (m) (t, 11.0) (dd, 5.5, 11.5)

(s) (br d, 6.6) (dd, 4.1, 14.0) (dd, 3.8, 14.0) (t, 4.0)

6.83 (s)

6.90 3.76 3.89 3.31 3.58 2.86 2.63 2.16

(s) (3H, s) (3H, s) (3H, s) (3H, s) (dd, 3.8, 15.0) (dd, 8.5, 15.0) (3H, s)

69.2 C 143.2 C 127.6 CH 64.1 CH 43.2 CH2

5.62 4.03 3.30 2.90 2.93

24.9 CH2 128.3 C 132.5 C 110.9 CH 148.5 C 149.4 C 113.3 CH 56.5 CH3 56.4 CH3 56.4 CH3

(dd, 2.1, 10.1) (d, 10.1) (m) (t, 11.0) (dd, 5.5, 11.5)

(s) (dd, 5.4, 6.4) (m) (m) (m)

6.79 (s)

6.73 3.68 3.79 3.29

47.3 CH2

(s) (3H, s) (3H, s) (3H, s)

66.6 C 158.7 C 118.1 CH 171.4 C 77.7 CH 80.4 CH 126.7 C 127.0 C 107.7 CH 149.0 C 148.0 C 109.9 CH 56.1 CH3 56.2 CH3 56.5 CH3 58.8 CH3

(dd, 2.4, 10.3) (d, 2.1, 10.2) (m) (dd, 10.0, 12.0) (dd, 4.5, 12.0)

6.03 (s) 5.42 (d, 5.5) 4.60 (d, 5.5)

6.84 (s)

7.17 3.84 3.73 3.34 3.78

(s) (3H, (3H, (3H, (3H,

s) s) s) s)

2.93 (m) 2.63 (m) 2.17 (3H, s)

30.8 CH3 210.5 C

1

H-NMR and 13C-NMR data were similar to those of (+)-erythristemine (11) (Juma and Majinda, 2004), except for the existence of an additional acetonyl group at C-8 in 1, which was supported by the HMBC correlations of δH 2.63 and 2.86 (H-CH2CO) to δC 64.9 (C-8), δC 126.7 (C-7), and δC 208.0 (C-CO), of δH 5.63 (H-7) to 64.9 (C-8), δC 67.6 (C-5),

and 5.63), four methoxyls (δH 3.89, 3.76, 3.58, 3.31), and one methyl (δH 2.16). In the 13C-NMR and DEPT spectra (Table 1) of 1, twentythree carbon resonances were observed, including three methylenes, four methoxyls, one methyl, three sp3 and five sp2 methines, one sp3 and five sp2 quaternary carbons, and one carbonyl carbon. The above 2

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and δC 141.2 (C-6). Its ROESY correlations of δH 4.02 (H-3)/δH 6.83(H14) together with coupling constants of H-4 suggested an α-orientation of 3-OMe. The ROESY spectrum also gave correlations of H-3 (δH 4.02)/ H-4β (δH 2.43), H-4β (δH 2.43)/H-11 (δH 4.16), H-11 (δH 4.16)/H-10α (δH 3.39), H-10β (δH 3.16)/H-8 (δH 4.46), which demonstrated the relative configuration of H-11 was α-oriented and H-8 was β-oriented. Thus, the structure of 1 was determined as (+)-8α-acetonylerythristemine, a previously undescribed natural compound. This was the first report of 8α-acetonyl erythrinan alkaloid. 8α-Acetonylerysotrine (2) was obtained as a yellow amorphous solid. The molecular formula was assigned as C22H27NO4 based on its HRESIMS (m/z 370.2008 [M+H]+), with 10 indices of hydrogen deficiency. Compared the NMR data of 2 with those of 1 (Table 1) and 13 (Amer et al., 1991), an 8-acetonyl group was also present in 2, while the 11-OMe was absent in 2. Thus, the structure of 2 was determined as (+)-8α-acetonylerysotrine. 10β-Hydroxy-11β-methoxyerysotramidine (3) was obtained as a yellow amorphous solid. The molecular formula was assigned as C20H23NO6 based on its HRESIMS (m/z 396.1424 [M+Na]+), with 9 degrees of unsaturation and one more oxygen atom than that of 11βmethoxyerysotramidine (4) (Juma and Majinda, 2004). Its 13C-NMR spectra (Table 1) were very similar to that of 4, except for the presence of an oxygenated CH, and the absence of a sp3 CH2 in 3. In the HMBC spectrum, the correlations from H-11 (δH 4.60) to the carbon at δC 77.7 (C-10) showed C-10 was oxygenated. The ROESY correlations of δH 3.81 (H-3)/δH 6.84 (H-14) together with coupling constants of H-4 suggested an α-orientation of 3-OMe. The ROESY correlation of H-3 (δH 3.81) to H-11 (δH 4.60) and H-10 (δH 5.42), H-4β (δH 2.96) to H-11(δH 4.60), H-10 (δH 5.42) and H-3 (δH 3.81) showed H-10 and H-11 were both α-oriented. Therefore, the structure of 3 was determined as 10β-hydroxy-11βmethoxyerysotramidine, an undescribed natural compound. 3-Epierysotrine (15) was obtained as a yellow amorphous solid. The molecular formula was assigned as C19H24NO3 based on its HRESIMS (314.1762 [M+H] +), with 9 indices of hydrogen deficiency. Its 13CNMR spectra were very similar to that of (+)-erysotrine (13) (Amer et al., 1991), except for the fact that the carbons of A-ring showed upfield chemical shift or downfield shift (Table 2) respectively in 15.

Compound 15 [ [α]D19.8 +189.2 (c 0.383, CH3OH)] was not the enantiomer of 13 [ [α]D19.8 +147.1 (c 0.100, CH3OH)] based on their optical rotation. So the possible structure of 15 was 3S, 5S- or 3R, 5R-. The calculated electronic circular dichroism (ECD) spectra of 3S, 5Sbetter matched the experimental ECD spectra of 15 by comparison (Fig. 2), which suggested the 3S, 5S- absolute configuration for 15. Hence, the structure of 15 was elucidated to be 3-epierysotrine. To date, the absolute configuration of all reported 3-subsitiuted erythrinan alkaloids were 3R (Tang et al., 2012). This is the first report of 3S erythrinan alkaloid. S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxypyrrolidin-2-one (18) was obtained as a yellow amorphous solid. Its molecular was established C13H17NO4 based on its HRESIMS at 252.1228 [M+H]+, with 6 degrees of unsaturation. The 1H NMR spectrum of 18 revealed the presence of an ABX benzene ring [δH 6.84 (dd, J = 7.9 Hz), 6.74 (d, J = 1.7 Hz), 6.69 (dd, J = 7.9, 1.9 Hz)]. Its 13C-NMR spectrum (Table 3) also showed three aromatic methines and three aromatic quaternary carbons, together with one carbonyl, one oxygenated methine, one methoxyl and four methylenes. In the HMBC spectrum, the correlations from H-7′ to C-2′, C-6′ and C-1′ suggested that the methylene group of C-7′ was attached to C-1′ of the benzene ring. Correlations from H-8′ to C-1′, C-7′, C-2 and C-5 suggested that the methylene group of C-8′ was attached to C-7′ and N of a 5-hydroxypyrrolidin-2-one ring. Therefore, compound 18 was identified as an undescribed pyrrolidine derivative. The absolute configuration of 18 was determined to be S by comparison of the experimental and calculated ECD spectra (Fig. 2). Hence, the structure of 18 was elucidated to be S-1-(4-hydroxy3-methoxyphenethyl)-5-hydroxy pyrrolidin-2-one. N-(3-hydroxy-4-methoxyphenethyl)-4-hydroxybutanamide (19) was obtained as a yellow amorphous solid. Its molecular formula was established as C13H19NO4 based on its HRESIMS at 254.1389 [M+H]+, with 5 degrees of unsaturation (one less than that of 18). Its 1H-NMR and 13C-NMR data (Table 3) resembled those of 18, with exception for the presence of an oxygenated CH2, and the absence of an oxygenated CH in 19. Possibly, the pyrrole ring was open. The unsaturation degree, and the HMBC correlations from H-8′, H-2 and H-3 to C-1 confirmed the assumption. Thus, the structure of 19 was established as N-(3-hydroxy4-methoxyphenethyl)-4-hydroxybutanamide. 2.2. Hypothetical biogenetic pathways of compounds 16–19

Table 2 1 H NMR (500 MHz) and 13C NMR (125 MHz) assignments of compounds 13 and 15 in CD3OD (ppm, J in Hz in parentheses). position

15

It's very interesting that compounds 16–19, which may be closely related in biosynthesis, were isolated from this plant at the same time. L-Tyrosine can be transformed to dopamine via oxygenation and decarboxylation. Condensation of substituent dopamine 16 with α-ketoglutaric acid (from glutamic acid) to imine followed by PictetSpengler cyclization generates the isoquinoline core. Lactamization of the resulting isoquinoline leads to pyrrolo [2,1-a]isoquinoline 17. The decarboxylation of imine followed by imino reduction and lactamization generates corresponding pyrroline 18; or followed by imino and carboxyl group reduction, then by oxygenation generates corresponding acid amide 19 (Fig. 3). The coexistence of compounds 16–19 supports the hypothetical biogenetic pathway of pyrrolo[2,1-a]isoquinoline proposed by Ulrike Passler and Hans-Joachim Knolker (Passler and Knolker, 2011).

13

δC, type

δH (J in Hz)

δC, type

δH (J in Hz)

1 2 3 4

124.6 CH 135.5 CH 76.5 CH 39.0 CH2

6.71 6.29 4.09 2.10 2.83

125.3 CH 131.5 CH 77.6 CH 41.7 CH2

6.60 6.05 4.06 1.79 2.53

(dd, 2.1, 10.2) (d, 10.2) (m) (t, 11.2) (dd, 5.6, 11.2)

5 6 7 8

72.7 C 141.4 C 120.4 CH 57.9 CH2

10

44.7 CH2

11

24.4 CH2

5.75 3.60 3.51 3.44 2.95 2.69 2.95

(s) (dd, 2.9, 14.6) (d, 14.6) (m) (m) (m) (m)

12 13 14 15 16 17 15-OCH3 16-OCH3 3-OCH3

125.0 127.0 110.1 149.8 151.2 113.3 56.6 56.5 57.0

C C CH C C CH

5.96 4.23 4.06 3.93 3.48 3.20 3.20

(dd, 1.9, 10.4) (d, 10.4) (brs) (t, 10.6) (dd, 5.4, 10.6)

(s) (d, 15.0) (d, 15.0) (m) (m) (t, 5.8) (t, 5.8)

6.74 (s)

6.91 3.71 3.84 3.36

(s) (3H, s) (3H, s) (3H, s)

68.0 C 143.7 C 123.6 CH 57.1 CH2 44.2 CH2 24.6 CH2 127.6 127.0 111.0 148.6 149.5 113.3 56.6 56.5 56.4

C C CH C C CH

2.3. Bioassays Using the MTS method reported in the literature (Zhang et al., 2017), compounds 1, 3, 15, 18 and 19 were tested for their cytotoxicity against the HL-60 (acute leukemia), SMMC-7721 (liver cancer), A-549 (lung cancer), MCF-7 (mammary cancer) and SW-480 (colon cancer) human tumor cell lines, but no activity was noted with IC50 values more than 40 μM. The AchE inhibitory activity of compounds 1, 3, 15, 18 and 19 were assayed using the Ellman method with slightly modification (Ingkanina et al., 2006). Compounds 3 and 18 (both 50 μM)

6.72 (s)

6.79 3.78 3.67 3.31

(s) (3H, s) (3H, s) (3H, s)

3

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Fig. 2. The experimental and calculated ECD spectra of 15 and 18 in CH3OH(left: 15; right: 18).

3. Experimental

Table 3 1 H NMR (500 MHz) and 13C NMR (125 MHz) assignments of compounds 18 and 19 (18 in CDCl3, 19 in CD3OD, ppm, J in Hz in parentheses). position

18 δC, type

1′ 2′ 3′ 4′ 5′ 6′ 7′ 8′

130.8 C 111.3 CH 146.6 C 144.3 C 114.4 CH 121.3 CH 33.8 CH2 41.9 CH2

1 2 3

174.6 C 28.8 CH2

4

28.5 CH2

5 OCH3

83.8 CH 55.9

3.1. General experimental procedures

19 δH (J in Hz)

6.74 (d, 1.7)

6.84 (d, 7.9) 6.84 (d, 7.9, 1.7) 2.84 (2H, m) 3.44–3.38 (m) 3.71–3.65 (m)

2.55 2.31 2.31 1.83 4.99 3.87

(m) (overlap) (overlap) (m) (d, 3.9) (3H, s)

δC, type

Optical rotations were measured with a Horiba SEAP-300 spectropolarimeter. NMR spectra were acquired on Bruker DRX-500. MS data were obtained using Bruker micrOTOF spectrometers. Fractions were monitored by TLC on silica gel plates (GF254, Qingdao Puke separation material Co., Ltd., Qingdao, China). Column chromatography (CC) was performed on silica gel (100–200 mesh or 200–300 mesh; Qingdao Puke separation material Co., Ltd., Qingdao, China), Sephadex LH-20 (GE Healthcare) and MCI gel (75–150 mm, Mitsubishi Chemical Corporation, Tokyo, Japan).

δH (J in Hz)

132.0 C 113.4 CH 148.9 C 146.0 C 116.2 CH 122.3 CH 36.1 CH2 42.2 CH2

6.74 6.66 2.73 3.39

175.8 C 33.7 CH2 29.8 CH2

2.26 (2H, t, 7.4) 1.81 (2H, m)

62.3 CH2

3.56 (2H, t, 6.9)

6.81 (d, 1.9)

(d, 8.0) (dd, 1.9, 8.0) (2H, t, 7.4) (2H, t, 7.1)

3.2. Plant material The stem barks of Erythrina stricta Roxb. (Leguminosae) were collected from Lujiang town, Baoshan district of Yunnan, China in February 2017. A voucher specimen (No. 17E01) was identified by Dr. Hongzhe Li (College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine) and deposited at the lab of Department of Chemistry and Chemical Engineering, Yunnan Normal University.

56.4

showed weak acetylcholinesterase inhibitory activity with percentage inhibition of 24.36% and 24.36% respectively, compared with 54.74% for tacrine (0.333 μM).

3.3. Extraction and isolation The powdered barks (17 kg) of Erythrina stricta were extracted with 95%EtOH at room temperature, which afforded a dark residue (1.34 kg)

Fig. 3. Hypothetical biogenetic pathways of compounds 16–19. 4

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(1.74) nm; [α]D19.8 -28.0 (c 0.371, CH3OH); Positive ESIMS: m/z 274 [M+Na]+, Positive HR-ESI-MS: 252.1228 [M+H]+ (calcd for C13H18NO4, 252.1230). 1H NMR and 13C NMR data, see Table 3.

after evaporation under reduced pressure. The residue was dissolved in H2O and extracted by EtOAc and n-BuOH successively. The EtOAc extract (300 g) was subjected to CC (SiO2, 100–200 mesh; petroleum ether/EtOAc 10:1, 8:1, 6:1, 4:1, 2:1, 1:1, 0:1) to gain eighteen fractions (Fr.1-Fr.18), and then it was eluted with CH3OH to afford fraction Fr.19. The n-BuOH extract (20 g) was subjected to CC (SiO2, 100–200 mesh; CHCl3/CH3OH 20:1, 15:1, 10:1, 5:1, 1:1, 0:1) to gain six fractions (Fr.20 - Fr.25). Fr.17 (5.2 g) was subjected to CC (SiO2, petroleum ether/EtOAc 1:1) to obtain three subfractions (Fr.17a-Fr.17c). Fr.17b (2.4 g) was resubjected to CC (SiO2, petroleum ether/CH3COCH3 3:2; CHCl3/ CH3COCH3 5:1) to provide compounds 17 (12.6 mg) and 9 (8.3 mg). Fr.19 (170 g) was subjected to CC (SiO2, CHCl3/CH3OH 25:1, 20:1, 15:1, 10:1, 5:1, 0:1) to obtain twelve subfractions (Fr.19a- Fr.19l). Fr.19d (2.2 g) was subjected to CC (SiO2, petroleum ether/CH3COCH3 3:2-1:1, CHCl3/CH3COCH3 4:1, CHCl3/CH3OH 20:1-8:1; Sephadex LH20, CHCl3/CH3OH 1:1) repeatedly to yield compounds 11 (104.1 mg), 7 (14.3 mg), 5 (31.2 mg), 18 (5.2 mg), 1 (8.8 mg), 3 (8.2 mg), and 4 (30.0 mg). Fr.19f (4.0 g) was subjected to CC (SiO2, petroleum ether/ CH3COCH3 3:2-1:1, CHCl3/CH3COCH3 3:1, CHCl3/CH3OH 15:1-8:1) repeatedly to get compounds 10 (19.7 mg), 2 (11.0 mg), 8 (31.0 mg) and 13 (90.0 mg). Fr.19g (2.2 g) was subjected to CC (SiO2, CHCl3/ CH3COCH3 3:1, petroleum ether/CH3COCH3 3:1-1:1, CHCl3/CH3OH 20:1-15:1; Sephadex LH-20, CHCl3/CH3OH 1:1) repeatedly to afford compounds 14 (11.0 mg), 19 (20.0 mg) and 6 (8.0 mg). Fr.21 (4.1 g) was subjected to CC (SiO2, CHCl3/CH3OH 20:1) to obtain five subfractions (Fr.21a- Fr.21e). Fr.21d (0.7 g) was subjected to CC (SiO2, CHCl3/CH3OH 15:1; CHCl3/CH3COCH3 4:1) to give compound 12 (7.8 mg). Fr.21e (0.5 g) was subjected to CC (SiO2, CHCl3/ CH3OH 15:1; petroleum ether/EtOAc 1:5) to get compound 15 (36.9 mg). Fr.24 (2.2 g) was subjected to CC (SiO2, petroleum ether/ CH3COCH3 1:5) to give nine subfractions (Fr.24a- Fr.24i). Fr.24h (1.1 g) was subjected to CC (SiO2, CHCl3/CH3OH 15:1-6:1; petroleum ether/EtOAc 1:6) to get compound 16 (18.0 mg).

3.4.6. N-(3-hydroxy-4-methoxyphenethyl)-4-hydroxybutanamide (19) Yellow amorphous solid; Positive ESIMS: m/z 276 [M+Na]+, Positive HR-ESI-MS: 254.1389 [M+Na]+ (calcd for C13H20NO4, 254.1387). 1H NMR and 13C NMR data, see Table 3. 3.5. Computational calculation ECD Monte Carlo conformational searches were carried out by means of the Spartan's 10 software using Merck Molecular Force Field (MMFF). The conformers with Boltzmann-population of over 5% were chosen for ECD calculations, and then the conformers were initially optimized at B3LYP/6–31 + g (d, p) level in MeOH using the CPCM polarizable conductor calculation model. The theoretical calculation of ECD was conducted in MeOH using Time-dependent Density functional theory (TD-DFT) at the B3LYP/6–31 + g (d, p) level. ECD spectra were generated using the program SpecDis 1.6 (University of Würzburg, Würzburg, Germany) and GraphPad Prism 5 (University of California San Diego, USA) from dipole-length rotational strengths by applying Gaussian band shapes with sigma = 0.3 eV. Notes The authors declare no competing financial interest. Acknowledgements This research was funded by the National Natural Science Foundation of China (No. 31460085). Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.phytochem.2019.112220.

3.4. Spectroscopic data of compounds

References

3.4.1. 8α-acetonylerythristemine (1) Yellow amorphous solid; UV(MeOH): λmax (log ε) = 202 (3.14), 230 (2.81), 278 (2.19) nm; [α]D20.3 + 8.44 (c 0.326, CH3OH); Positive ESIMS: m/z 400 [M+H]+, Positive HR-ESI-MS: 400.2133 [M+H]+ (calcd. for C23H30NO5, 400.2118).1H NMR and 13C NMR data, see Table 1.

Akter, K., Barnes, E.C., Loa-Kum-Cheung, W.L., Yin, P., Kichu, M., Brophy, J.J., Barrow, R.A., Imchen, I., Vemulpad, S.R., Jamie, J.F., 2016. Antimicrobial and antioxidant activity and chemical characterisation of Erythrina stricta Roxb. (Fabaceae). J. Ethnopharmacol. 185, 171–181. Amer, M.E., Shamma, M., Freyer, A.J., 1991. The tetracyclic erythrina alkaloids. J. Nat. Prod. 54, 329–363. Chawla, A.S., Chunchatprasert, S., Jackson, A.H., 1983. Studies of erythrina alkaloids Ⅶ-13C NMR spectral studies of some erythrina alkaloids. Org. Magn. Reson. 21, 39–41. Cui, Y.L., Shen, N., Zhao, J.Q., Dang, J., Shao, Y., Mei, L.J., Wang, Q.L., Tao, Y.D., Liu, Z.G., 2017. Phytochemical constituents of Arenaria kansuensis. Chem. Nat. Compd. 53 (5), 1002–1004. Fahmy, N.M., Al-Sayed, E., El-Shazly, M., Singab, A.N., 2018. Comprehensive review on flavonoids biological activities of Erythrina plant species. Ind. Crops Prod. 123, 500–538. Ingkanina, K., Changwijit, K., Suwanborirux, K., 2006. Vobasinyl-iboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricate root. J. Pharm. Pharmacol. 58, 847–852. Juma, B.F., Majinda, R.R.T., 2004. Erythrinaline alkaloids from the flowers and pods of Erythrina lysistemon and their DPPH radical scavenging properties. Phytochemistry 65, 1397–1404. Lee, S.K., 1995. Flora Reipublicae Popularis Sinicae, vol. 41. Science Press, Beijing, pp. 169. Parsons, A.F., Palframan, M.J., 2010. Erythrina and related alkaloids. Alkaloids - Chem. Biol. 68, 39–81. Passler, U., Knolker, H.J., 2011. The pyrrolo[2,1-a] isoquinoline alkaloids. Alkaloids Chem. Biol. 70, 79–151. Selvam, C., Jordan, B.C., Prakash, S., Mutisya, D., Thilagavathi, R., 2017. Pterocarpan scaffold: a natural lead molecule with diverse pharmacological properties. Eur. J. Med. Chem. 128, 219–236. Tang, Z.R., Wang, L.Q., Ye, G.D., 2012. Alkaloids of Erythrina species and their biological activities. Guangzhou Chem. Ind. 40, 43–46. Wandji, J., Suhi, A., Fomum, Z.T., Tillequin, F., Libot, F., 1995. Isoflavones and alkaioids

3.4.2. 8α-acetonylerysotrine (2) Yellow amorphous solid; Positive ESIMS: m/z 393 [M + H + Na]+, Positive HR-ESI-MS: 370.2008 [M+H]+ (calcd for C22H28NO4, 370.2013). 1H NMR and 13C NMR data, see Table 1. 3.4.3. 10-Hydroxy-11β-methoxyerysotramidine (3) Yellow amorphous solid; UV(MeOH): λmax(log ε) = 203 (3.08), 237 (2.69) nm; [α]D19.8 +84.4 (c 0.362, CH3OH); Positive ESIMS: m/z 396 [M+Na]+, Positive HR-ESI-MS: 396.1424 [M+Na]+ (calcd for C20H23NO6Na, 396.1418). 1H NMR and 13C NMR data, see Table 1. 3.4.4. 3-Epierysotrine (15) Yellow amorphous solid, UV(MeOH): λmax (log ε) = 203 (3.07), 232 (2.73), 282 (2.02) nm; [α]D19.8 +189.2 (c 0.383, CH3OH); Positive ESIMS: m/z 314 [M+ H]+, Positive HR-ESI-MS: 314.1762 [M+H]+ (calcd for C19H24NO3, 314.1751). 1H NMR and 13C NMR data, see Table 2. 3.4.5. S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxypyrrolidin-2-one (18) Yellow amorphous solid, UV(MeOH): λmax (log ε) = 200 (2.81), 280 5

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