Formation of Samin Diastereomers by Acid-Catalyzed Transformation of Sesamolin with Hydrogen Peroxide

Article abstract of DOI:10.1021/acs.jafc.0c01616

The conversion of sesame lignans is of interest because the derived products may have potential applications. Here, in investigating the transformation of sesamin and sesamolin, main endogenous sesame lignans in sesame seeds, in both acidic aqueous and anhydrous systems, 7R,7′S-samin was identified as one of the major products of sesamolin in both systems catalyzed with common inorganic acids, but sesaminol was not generated. In investigating the effect of different oxidizing agents on the acid-catalyzed conversion of sesame lignans, 7R,7′S-samin was still the major product of sesamolin, whereas sesamolin as well as 7R,7′S-samin stereoselectively rendered 7R,7′R-samin in the presence of hydrogen peroxide. Hydrogen peroxide may play a role in stabilizing the transitional oxonium ions, derived from acid hydrolysis of sesamolin or 7R,7′S-samin by forming a seven-membered ring intermediate through hydrogen bonding, to consequently produce 7R,7′R-samin as the final product.

Full text of DOI:10.1021/acs.jafc.0c01616

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Food and Beverage Chemistry/Biochemistry
Formation of Samin Diastereomers by Acid-catalyzed
Transformation of Sesamolin with Hydrogen Peroxide
Hsin-Ya Tsai, Wei-Ju Lee, I-Hsuan Chu, Wei-Ching Hung, and Nan-Wei Su
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.0c01616 • Publication Date (Web): 12 May 2020
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Journal of Agricultural and Food Chemistry
Formation of Samin Diastereomers by Acid-catalyzed Transformation of Sesamolin with
Hydrogen Peroxide
1
,§
2,3,§
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1*
Authors: Hsin-Ya Tsai , Wei-Ju Lee , I-Hsuan Chu , Wei-Ching Hung , and Nan-Wei Su
1Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan
2School of Food Safety, Taipei Medical University, Taipei 11042, Taiwan
3Master program in Food Safety, Taipei Medical University, Taipei 11042, Taiwan
§Both authors contributed equally to this work
*
*
Corresponding author:
Nan-Wei Su, Ph.D., Professor
Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan
Tel: +886-2-33664806
Fax: +886-2-23632714
E-mail: snw@ntu.edu.tw
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ABSTRACT
The conversion of sesame lignans is of interest because the derived products may have potential
applications. Here, in investigating the transformation of sesamin and sesamolin in both acidic
aqueous and anhydrous systems, 7R,7’S-samin was identified as one of the major products of
sesamolin in both systems catalyzed with common inorganic acids, but sesaminol was not generated.
In investigating the effect of different oxidizing agents on the acid-catalyzed conversion of sesame
lignans, 7R,7’S-samin was still the major product of sesamolin, whereas sesamolin stereo-selectively
rendered 7R,7’R-samin in the presence of hydrogen peroxide. Hydrogen peroxide may play a role in
stabilizing the transitional oxonium ions, derived from acid hydrolysis of sesamolin by forming a
seven-membered ring intermediate through hydrogen bonding, to consequently produce
7R,7’R-samin as the final product.
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KEYWORDS: sesame oil, furofuran lignans, sesamolin-derivative, acid-catalyzed transformation,
samin diastereomers, hydrogen peroxide
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INTRODUCTION
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Sesame oil produced from seeds of Sesamum indicum is considered a nutritious and stable edible oil.
Sesame seed is one of the major plant sources of furofuran lignans, which have numerous
physiological activities. The main agluconic lignans in sesame seeds are sesamin and sesamolin.
Sesamin and sesamolin have a variety of biological activities, such as anti-oxidation,
hypocholesterolemic, hepatoprotective, antihypertension, and neuroprotective properties.1-5
Meanwhile, sesame oil is also known for its superior oxidative stability. Despite its high level of
unsaturated fatty acids, sesame oil is relatively stable against oil deterioration as compared with other
dietary oils.6-10 The resistance of sesame oil to oxidation was mainly attributed to the presence and
synergy of minor components including lignans, lignan derivatives, tocopherols, and Maillard
reaction products generated when sesame seeds are roasted.6, 10-13 As a result, oil processing may
affect the configuration of sesame lignans and play an important role in enhancing sesame oil’s
oxidative stability.
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Several studies have reported the changes in lignans composition during each step of the
manufacturing process of sesame oil.14-17 During the processing, sesamolin was converted to sesamol
under thermal conditions or rearranged to sesaminol under acid bleaching treatment.15-16 The other
main lignan, sesamin, was transformed to episesamin during acid bleaching and deodorization at
high temperature.15-16 The endogenous lignans, sesamin and sesamolin, are most abundant in sesame
oils but possess relatively weak antioxidant activity.10, 13, 18-19 In contrast, sesamol and sesaminol,
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generated from sesamolin during processing, show strong in vitro antioxidant activity and were
therefore considered responsible for the strengthened oxidative stability of roasted and refined
unroasted sesame oils 10, 15, 18-19 Therefore, studies of the transformation of sesame lignans are of high
interest because the relevant derivatives of lignans may possess better antioxidant activities than
endogenous lignans in sesame oil or possess physiological activities. The chemical structures of
sesame lignans and the derivatives sesamin, sesamolin, sesamol, sesaminol, and samin are illustrated
in Figure 1.
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Studies of the acid-catalyzed transformation of sesame lignans are limited. Most studies focused on
the conversion of sesamolin to sesaminol in acidic anhydrous systems.15-16, 20-21 In this work, strong
acids and oxidizing agents were used to treat sesame lignans to generate derived compound(s) in
aqueous or anhydrous systems. Reaction products of sesame lignans from acid-catalyzed reactions
were isolated and identified to elucidate the transformation of sesame lignans. Also, the possible
mechanism for formation of the major derivative, 7R,7’R-samin, from sesamolin treated with
acidified hydrogen peroxide was clarified.
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MATERIALS AND METHODS
Materials
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The lignan standards sesamin, sesamolin, and sesamol were purchased from Sigma-Aldrich (St.
Louis, MO, USA). Sesaminol and (+)-samin (7R,7’S-samin) were purchased from Nacalai tesque
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(Kyoto, Japan). Solvents used in this study including acetic acid, acetonitrile, methanol, ethyl acetate
were purchased from J. T. Baker (Phillipsburg, NJ, USA). Toluene was purchased from Merck
(Darmstadt, Germany). Sulfuric acid and formic acid were purchased from Sigma-Aldrich (St. Louis,
MO, USA). Oxidizing agents including hydrogen peroxide 30%, potassium permanganate (KMnO4),
and potassium dichromate (Kr Cr O ) were purchased from Echo Chemical (Miaoli, Taiwan),
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Hayashi Pure Chemical (Osaka, Japan), and Sigma-Aldrich (St. Louis, MO, USA), respectively. All
chemicals and reagents used were of reagent or analytical grade.
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Acid-catalyzed transformation of sesame lignans in aqueous solution
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According to previous studies, the transformation of sesame lignans was severely affected by the
presence of water in the reaction system. For example, sesamolin is decomposed and converted into
samin in acidic aqueous solution but into sesaminol under the acidic anhydrous condition.15-16, 20-21
Therefore, a preliminary test for transforming sesame lignans in acidic aqueous solution was first
investigated. Briefly, a 10-mg reaction substrate, comprising 6.2 mg sesamin and 3.8 mg sesamolin,
was added into 10 mL 2 M sulfuric acid at 60°C with occasional stirring for 0, 5, 15, 30, 60 min.
Then, 10 mL ethyl acetate was added to the reaction mixture to extract the reaction products. The
ethyl acetate layer was dried under reduced pressure for further lignan analysis.
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Acid-catalyzed transformation of sesame lignans in anhydrous toluene
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The transformation of sesame lignans in the anhydrous system was investigated. In brief, 2 mL of
conc. sulfuric acid and formic acid were gently added into 2 mL toluene, containing 0.62 mg sesamin
and 0.38 mg sesamolin as a reaction substrate, at room temperature with occasional stirring for 10
min. The organic layer was dried under reduced pressure for further lignan analysis.
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Acid-catalyzed transformation of sesame lignans with oxidizing agents
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Under certain conditions, sesame lignans could be transformed to their oxidized forms, which
sometimes possess better antioxidant activities than their original forms.22-23 In this work, sesamin
and sesamolin were treated with different oxidizing agents to elucidate the effect of oxidizing agents
on the transformation of lignans. In brief, a reaction substrate comprising 6.2 mg sesamin and 3.8 mg
sesamolin was reacted with 10 mL with 10 mL 180 mM sulfuric acid solution containing oxidizing
agents including 3 mM potassium permanganate, 3 mM potassium dichromate, or 30% hydrogen
peroxide. The reaction mixture was incubated at 60°C with occasional stirring for 30 min and
extracted with 10 mL ethyl acetate. The ethyl acetate layer was dried under reduced pressure for
further lignan analysis.
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Analysis of sesame lignans and related derivatives by HPLC
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The lignan samples from the aforementioned processes were dissolved in methanol, then filtered by a
0.45-µm membrane filter to remove insoluble matters for HPLC analysis. An analytical Shimadzu
LC-10AD HPLC system (Shimadzu, Kyoto, Japan) equipped with a YMC-Pack ODS-AM column
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(250 x 4.6 mm, 5 µm) (YMC, Kyoto, Japan) and a L-2420 Hitachi UV/vis detector (Hitachi, Tokyo,
Japan) was used. The linear mobile phase gradient was obtained with 0.1% (v/v) acetic acid in
ultrapure water (solvent A) and 0.1% (v/v) acetic acid in methanol (solvent B). Following the
injection of 20 µL sample, solvent B was increased from 45% to 90% over 25 min, then to 100%
within 3 min, was isocratic for another 2 min, and finally decreased to 45% within 7 min. Before
injection of the next sample, the column was equilibrated with solvent B at 45% for 10 min. The
flow rate of 1 mL/min was used and the elute was detected at 290 nm. The data were processed by
using the SISC chromatography data station v.3.1 (SISC, Taipei, Taiwan).
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Isolation and identification of 7R,7’S-samin and 7R,7’R-samin
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The separation and isolation of 7R,7’S-samin and 7R,7’R-samin were performed on a
semi-preparative-scale HPLC system equipped with a Hypersil ODS C18 column (250 x 10 mm, 10
µm) (Thermo Fisher Scientific, Waltham, MA, USA). The linear mobile phase gradient was obtained
with ultrapure water (solvent A) and methanol (solvent B). Following the injection of 100 µL of
sample, solvent B was increased from 30 to 50% over 20 min, then to 75% in 1 min, isocratic for 4
min, decreased from 75 to 30% in another 3 min, and equilibrium for 5 min. The flow rate was 5.0
mL/min. The eluates were collected and monitored at 290 nm. Fractions containing the desired
eluates were further concentrated and lyophilized to obtain a pale amorphous powder for further
chemical structure identification.
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7R,7’S-samin and 7R,7’R-samin were identified according to the data from electrospray ionization
mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. The electrospray
ionization mass spectrometer (Thermo Q Exactive Plus, Thermo Finnigan LXQ Aadvantag, Thermo
Fisher Scientific, CA, USA) included a hybrid quadrupole-Orbitrap analyzer (Thermo Fisher
Scientific, CA, USA). The electrospray ionization source (HESI-II) was operated in the positive
ionization mode under the following specific conditions: capillary temperature, 262.5 °C; spray
voltage, 3.5 kV; sheath gas, 50 L/min; auxiliary gas, 12.5 L/min. The mass spectrometer performed a
full scan event (mass range m/z 100-1000) with a resolving power of 70,000 at full width at half
maximum (FWHM) at m/z 200 followed by 20 consecutive fragmentation events (variable data
independent acquisition [vDIA]) with a resolving power of 35000 at FWHM (m/z 200). NMR
spectra were recorded on a Bruker Avance 600 MHz NMR spectrometer (Bruker, Billerica, MA,
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USA). Chemical shifts (δ) and coupling constants (J) are expressed in ppm and Hz, respectively. H
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and C chemical shifts were calibrated with CDCl as internal standard at δ = 7.24 and 77.0,
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respectively.
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Statistical analysis
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All data analyses involved using SPSS 19.0. Data are reported as mean ± standard deviation (SD).
All experiments were performed in triplicate (n=3).
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RESULTS AND DISCUSSION
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Acid-catalyzed transformation of sesame lignans in aqueous solution
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Transformation of sesame lignans is influenced by the acid catalysts and solvents used. In previous
studies, sesamolin was supposedly directly degraded into sesamol and samin via acid hydrolysis in
the presence of water but converted to sesaminol via rearrangement of sesamol and the oxonium ion
in acidic anhydrous systems.15-16, 20-21 Epimerization of sesamin was also observed in acidic
anhydrous systems,15-16, 24 but the acidic transformation of sesamin in aqueous solution was not clear.
In this work, we studied changes of sesame lignans during acid treatment in aqueous solution.
Regardless of treatment with acids or not, peaks representing sesamin were unchanged (Figure 2a-c),
so sesamin possesses good stability under acidic aqueous solutions, and no episesamin was observed
under both conditions. In contrast, sesamolin was relatively unstable and depleted along with the
generation of sesamol and an unidentified compound, designated compound a (peak 4 in Figure
2a-c). Fractions containing compound a were further isolated and identified by ESI-MS and NMR
analysis.
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Identification of compound a
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The mass spectrum for compound a showed [M+Na] at 273.29 m/z with close relation to samin.
MS/MS spectrum for protonated ion of compound a was showed in Supplementary Figure 1a.
Analysis of the NMR spectra using HSQC, HMBC, and COSY experiments gave the full
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assignments of H and C signals. H-NMR and C-NMR spectral data for compound a were
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corresponded with NMR spectral data for (+)-samin isolated from sesame seeds (Table 1). From
the above spectral data, compound a was considered to be 7R,7’S-samin [(+)-samin], with a
methylenedioxyphenyl group on C7 and a hydroxyl group on C7’ with R and S configurations,
respectively. These results agree with that sesamolin is known to be decomposed into sesamol and
samin in acidic aqueous solution. Moreover, the hydrolysis of sesamolin catalyzed with sulfuric acid
released sesamol and 7R,7’S-samin simultaneously in the aqueous system (Figure 2d).
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Acid-catalyzed transformation of sesame lignans in anhydrous toluene
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As previously described, the presence of water is one of the important determinants for the
transformation of lignans. Sesame lignans were treated with sulfuric acid and formic acid in
anhydrous toluene to investigate the conversion of lignans in anhydrous system. Sesamin remained
unchanged, and no epimerization was observed (Figure 3). Meanwhile, sesamol and 7R,7’S-samin
were still the major products of sesamolin in both cases, whereas no sesaminol was formed (Figure
3). According to previous studies, sesamolin should scission into sesamol and the transitional
oxonium ion and then undergo rearrangement to form sesaminol in anhydrous solvent systems, such
as acid bleaching, toluene with camphorsulfonic acid, and toluene with acidic cation exchange resin
which possesses a sulfonic functional group.15-16, 20-21 However, sesaminol was not generated from
sesamolin treated with sulfuric acid or formic acid in toluene in our study, so the acid catalysts might
be crucial for the specific transformation of sesamolin into sesaminol. Otherwise, sesamolin was
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prone to be decomposed directly into sesamol and 7R,7’S-samin with common inorganic acids as
catalysts both in aqueous and anhydrous systems.
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Acid-catalyzed transformation of sesame lignans with oxidizing agents
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To generate derived compounds for further investigating the effect of oxidants on the conversion of
sesame lignans, sesamin and sesamolin prepared in sulfuric acid aqueous solution were treated with
the oxidizing agents potassium permanganate, potassium dichromate, and hydrogen peroxide.
Sesamolin was degraded, but sesamin was relatively stable (Figure 4). Also, the main transformation
products of sesamolin with different oxidizing agents varied. The main transformation products of
sesamolin with acidified potassium permanganate were still sesamol and 7R,7’S-samin, whereas
7R,7’S-samin was the only major product of sesamolin with acidified potassium dichromate (Figure
4b,c). Previous studies have reported that sesamol was relatively heat unstable as compared with
sesamin and sesaminol, especially with temperature above 200℃.15, 17 Sesamol seemed to be also
more unstable than 7R,7’S-samin with acidified potassium dichromate treatment, with 7R,7’S-samin
as the main product of sesamolin. In contrast, Figure 4d shows that sesamol and a new compound,
designated compound b (peak 5 in Figure 4d), were products after oxidation of sesamolin by
acidified hydrogen peroxide. Fractions containing compound b were further isolated and identified
by ESI-MS/MS and NMR analysis.
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Identification of compound b (7R,7’R-samin)
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Compound b was identified by ESI-MS/MS, UV-Vis and NMR spectra as 7R,7’R-samin, the
diastereomer of 7R,7’S-samin. Mass spectrum of compound b shows compound b has the same
molecular weight with 7R,7’S-samin. The MS/MS spectra for compound b and 7R,7’S-samin show
similar fragmentation patterns with 9 identical molecular-weight daughter ions (Supplementary
Figure 1). Also, UV-Vis absorption spectrum of compound b shows three major absorption peaks at
204, 235, 287 nm, which was close with that of 7R,7’S-samin (203, 238, 287 nm), indicating
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compound b has a high structural similarity with 7R,7’S-samin (Supplementary Figure 2). NMR
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spectral analysis including H, C, HSQC, HMBC, and COSY experiments affords the full
assignments for compound b, revealing that compound b and 7R,7’S-samin might be diastereomers
(Table 1, Table 2 and Supplementary Figure 3-8). According to Table 1 and Table 2, compound b
shows many similar proton or carbon chemical shifts and proton splitting patterns with 7R,7’S-samin,
but with several different chemical shifts between compound b and 7R,7’S-samin (Table 1 and Table
2). Among these differences, the deviation of chemical shifts for C7’ was the most marked with
102.2 ppm for 7R,7’S-samin and 111.7 ppm for compound b (Table 1 and Table 2). Other protons
(H7’, H8’, H9’a, H9’b, H8, H9a and H9b) or carbons (C8’ and C8) with slight different chemical
shifts for compound b and 7R,7’S-samin are all close to C7’, implicating compound b may have a
different configuration of hydroxyl group on C-7’ which causes these differences of chemical shifts
between compound b and 7R,7’S-samin (Table 1 and Table 2). Therefore, compound b was
concluded as 7R,7’R-samin. According to the above results, the major transformation product of
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sesamolin under acidified potassium permanganate and potassium dichromate treatment was
7R,7’S-samin, whereas sesamolin was preferentially converted into 7R,7’R-samin in the presence of
hydrogen peroxide.
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Possible mechanism for formation of 7R,7’R-samin in acidified hydrogen peroxide
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This study revealed the specific formation of 7R,7’R-samin catalyzed by hydrogen peroxide for the
first time, so we explored the possible role of hydrogen peroxide in forming 7R,7’R-samin in
acidified hydrogen peroxide. Sesamolin was mainly converted to sesamol and 7R,7’S-samin in
sulfuric acid, whereas 7R,7’R-samin was the major reaction product of sesamolin with hydrogen
peroxide present in the same acid (Figure 2b,c and Figure 4d). Therefore, we speculate that hydrogen
peroxide might be related to the epimerization of 7R,7’S-samin under acidic conditions. To verify
whether hydrogen peroxide could catalyze the epimerization of 7R,7’S-samin to form 7R,7’R-samin,
the 7R,7’S-samin standard was directly reacted with 30% hydrogen peroxide only and 30% hydrogen
peroxide in 180 mM sulfuric acid. 7R,7’R-samin was formed under both conditions, which suggests
that hydrogen peroxide alone was capable of converting 7R,7’S-samin into 7R,7’R-samin (Figure 5).
However, hydrogen peroxide without sulfuric acid could only catalyze the partial conversion of
7R,7’S-samin into 7R,7’R-samin, so the presence of acid may enhance the epimerization. Sesamolin
and sesamin were treated with hydrogen peroxide under different concentrations of sulfuric acid to
investigate the effect of acid on the catalytic efficiency of hydrogen peroxide for epimerization of
7R,7’S-samin. As expected, the formation of 7R,7’R-samin was increased with increasing
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concentration of sulfuric acid in the reaction system; furthermore, 7R,7’S-samin completely
transformed to 7R,7’R-samin when the concentration of sulfuric acid reached 50 mM (Figure 6).
Therefore, hydrogen peroxide was related to the epimerization of 7R,7’S-samin. In addition,
increasing sulfuric acid concentration might accelerate the epimerization.
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We further propose the possible formation mechanism of 7R,7’R-samin catalyzed by hydrogen
peroxide according to the stereochemical relationship to elucidate why hydrogen peroxide causes the
different configuration of the hydroxyl substituted group of samin. In the absence of hydrogen
peroxide, the nucleophilic hydroxyl group was more likely to attack the transitional oxonium ion
derived from sesamolin on the same side of the methylenedioxyphenyl group under acidic conditions
owing to the steric hindrance caused by the cis-fused furofuran ring (Figure 7a). Therefore, the main
product of sesamolin is usually 7R,7’S-samin under general acidic conditions. In contrast, hydrogen
peroxide is prone to approach the oxonium ion intermediate derived from acid hydrolysis of
sesamolin from the opposite site of the methylenedioxyphenyl group to stabilize a seven-membered
ring intermediate structure by forming hydrogen bonds with the oxonium ion, thus resulting in the
formation of 7R,7’R-samin as the final product (Figure 7b). Because hydrogen peroxide could
catalyze the formation of 7R,7’R-samin both from sesamolin and 7R,7’S-samin (Figure 4d and Figure
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5), we suggest that sesamolin and 7R,7’S-samin might be transformed into the transitional oxonium
ions first, then both be accessible to form hydrogen bonds with hydrogen peroxide and then
converted into 7R,7’R-samin. Although samin in racemic form has been synthesized via a radical
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cyclization reaction or an Ireland-Claisen rearrangement of unsaturated oxa-macrolides,26-29 the
stereo-selective formation of 7R,7’R-samin from sesamolin catalyzed with hydrogen peroxide was
first reported in this study.
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Overall, sesamolin was mainly converted into 7R,7’S-samin and sesamol under acidic conditions in
both aqueous and anhydrous systems in the present study, whereas the formation of sesaminol, which
was reported to be formed from sesamolin in acidic anhydrous systems, was not observed. The acidic
conversion of sesamolin into sesaminol may require specific catalysts; otherwise, the formation of
sesaminol would be minor even in acidic anhydrous systems. Also, both sesamolin and 7R,7’S-samin
were found specifically transformed into 7R,7’R-samin under catalysis with hydrogen peroxide. The
acid-catalyzed transformation pathway for sesamolin is summarized in Figure 8.
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Our findings broaden the current understanding of acid-catalyzed transformation of sesamolin under
different catalytic conditions. Moreover, the study proposes the possible mechanism for formation of
7R,7’R-samin via a stereo-selective reaction catalyzed by hydrogen peroxide under acidic conditions.
Characteristics such as the ability to delay oil deterioration and physiological activities of individual
stereoisomers of samin require further exploration. Recently, a series of furofuran lignans and
flavonolignans synthesized from 7R,7’S-samin as a starting material through a Friedel-Crafts–like
reaction were shown to possess β-glucosidase and free radical inhibition activities.30-31 The present
study may also help in preparing stereoisomers of samin or samin derivatives to further discover their
potential applications.
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FUNDING
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2
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The authors are grateful for the financial support from Flavor Full Foods Inc., Taipei (grant no.
NTU102E32034).
ABBREVIATIONS USED
2
2
2
2
2
2
2
58
59
60
61
62
63
64
HPLC, high-performance liquid chromatography
ESI-MS, electrospray ionization mass spectrometry
NMR, nuclear magnetic resonance
HSQC, heteronuclear single quantum coherence
HMBC, heteronuclear multiple bond correlation
COSY, correlation spectroscopy
REFERENCES
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268
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270
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sesame oil from raw and processed seeds. J. Food Lipids 1996, 3 (1), 59-72.
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of roasted sesame seed oil, and the effect of using the oil for frying. Agric. Biol. Chem. 1986, 50 (4),
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15. Fukuda, Y.; Nagata, M.; Osawa, T.; Namiki, M., Contribution of lignan analogues to
antioxidative activity of refined unroasted sesame seed oil. J. Am. Oil Chem. Soc. 1986, 63 (8),
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16. Moazzami, A. A.; Haese, S. L.; Kamal‐Eldin, A., Lignan contents in sesame seeds and products.
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during heating. Food Chem. 2007, 104 (1), 341-344.
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LC‐NMR‐MS characterization of sesame oil extracts and assessment of their antioxidant activity.
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19. Lee, J.; Choe, E., Extraction of lignan compounds from roasted sesame oil and their effects on
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20. Fukuda, Y.; Isobe, M.; Nagata, M.; Osawa, T.; Namiki, M., Acidic transformation of sesamolin,
the sesame-oil constituent, into an antioxidant bisepoxylignan, sesaminol. Heterocycles 1986, 24 (4),
923-926.
21. Huang, J.; Song, G.; Zhang, L.; Sun, Q.; Lu, X., A novel conversion of sesamolin to sesaminol
by acidic cation exchange resin. Eur. J. Lipid Sci. Technol. 2012, 114 (7), 842-848.
22. Kumano, T.; Fujiki, E.; Hashimoto, Y.; Kobayashi, M., Discovery of a sesamin-metabolizing
microorganism and a new enzyme. Proc. Natl. Acad. Sci. 2016, 113 (32), 9087-9092.
23. Murata, J.; Ono, E.; Yoroizuka, S.; Toyonaga, H.; Shiraishi, A.; Mori, S.; Tera, M.; Azuma, T.;
Nagano, A. J.; Nakayasu, M., Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates
twin dietary lignans in sesame. Nat. Commun. 2017, 8 (1), 2155.
24. Li, C.-Y.; Chow, T. J.; Wu, T.-S., The epimerization of sesamin and asarinin. J. Nat. Prod.
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25. Kuo, P.-C.; Lin, M.-C.; Chen, G.-F.; Yiu, T.-J.; Tzen, J. T., Identification of methanol-soluble
compounds in sesame and evaluation of antioxidant potential of its lignans. J. Agric. Food Chem.
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26. Maiti, G.; Adhikari, S.; Roy, S. C., Stereoselective total synthesis of (±)-Samin, the general
furofuran lignan precursor. Tetrahedron 1994, 35 (36), 6731-6732.
27. Maiti, G.; Adhikari, S.; Roy, S. C., Stereoselective total synthesis of (±)-samin and the
dimethoxy analogue, the general furofuran lignan precursors. Tetrahedron 1995, 51 (30), 8389-8396.
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28. Hull, H. M.; Knight, D. W., Diastereospecific approach to (±)-samin and 2, 6-diaryl-3,
7-dioxabicyclo [3.3. 0] octane (furofuran) lignans using the Ireland–Claisen rearrangement of
unsaturated oxamacrolides. J. Chem. Soc. Perkin Trans. I 1997, (6), 857-864.
29. Hull, H.; Jones, Ú.; Knight, D., An alternative diastereospecific approach to (±)-samin and 2,
6-diaryl-3, 7-dioxabicyclo [3.3. 0] octane [furanofuran] lignans based on the Ireland–Claisen
rearrangement of unsaturated oxa-macrolides. J. Chem. Soc. Perkin Trans. I 1998, (11), 1779-1788.
30. Worawalai, W.; Khongchai, P.; Surachaitanawat, N.; Phuwapraisirisan, P., Synthesis of
furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free
radical. Arch. Pharm. Res. 2016, 39 (10), 1370-1381.
31. Worawalai, W.; Phuwapraisirisan, P., Samin-derived flavonolignans, a new series of
antidiabetic agents having dual inhibition against α-glucosidase and free radicals. Nat. Prod. Res.
2018, 1-7.
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TABLES
Table 1. 1-D and 2-D NMR results for compound a (7R,7’S-samin)
Correlated carbons
Correlated protons
COSY
Proton
δ/ppm (m, J/Hz)
HSQC
52.8 (C8)
53.6 (C8’)
71.2 (C9’)
69.3 (C9)
69.3 (C9)
86.9 (C7)
71.2 (C9’)
102.2 (C7’)
101.0 (C10)
108.2 (C5)
HMBC
H8
H8’
H9’a
H9a
H9b
H7
2.87 (m)
3.04 (dd, 8.8, 16.4)
3.54 (dd, 7.2, 9.2)
3.88 (d, 9.2)
4.14 (dd, 6.0, 9.2)
4.32 (d, 7.0)
4.35 (t, 7.0)
C1
H7, H8’, H9a, H9b
H8, H9’a, H9’b
H8, H9’b
C7, C8
C7, C8
H8, H9b
C7
H8, H9a
C1, C2, C6, C8’, C9
C7
H8, H9’a
H9’b
H7’
H10
H5
H8’, H9’a
5.36 (s)
C8, C9, C9’
C3, C4
5.93 (s)
6.74 (d, 8.0)
C1, C3, C4
H6
H2
6.78 (dd, 1.2, 7.8)
6.83 (d, 1.2)
119.6 (C6)
106.5 (C2)
C1, C4, C5, C7
C3, C4, C6, C7
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Table 2. 1-D and 2-D NMR results for compound b (7R,7’R-samin)
Correlated carbons
HMBC
Correlated protons
COSY
Proton δ/ppm (m, J/Hz)
HSQC
52.5 (C8)
49.5 (C8’)
71.0 (C9’)
69.5 (C9)
69.5 (C9)
86.5 (C7)
71.0 (C9’)
111.7 (C7’)
101.1 (C10)
108.2 (C5)
119.6 (C6)
106.4 (C2)
H8
H8’
H9’a
H9a
H9b
H7
2.76 (m)
2.96 (dd, 8.4, 15.9)
3.62 (dd, 7.2, 9.6)
3.95 (d, 9)
C1, C7, C7’
C7, C7’
H7, H8’, H9b
H8, H9’a, H9’b
H8’, H9’b,
H9b
C7’, C8’
C7, C7’, C8, C8’
C7
4.04 (dd, 6, 9.3)
4.33 (d, 7.8)
H8, H9a
C1, C2, C6, C8, C8’, C9
C7, C7’, C8
C8, C8’, C9, C9’
C3, C4
H8
H9’b
H7’
H10
H5
4.38 (t, 9)
H8’, H9’a,
5.43 (s)
5.93 (d, 10.8)
6.75 (d, 8.4)
C1
H6
6.77 (dd, 1.2, 6.6)
6.82 (d, 1.2)
C1, C2, C4, C7,
C3, C4, C6, C7
H2
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FIGURE LEGENDS
Figure 1. The chemical structures of sesame lignans and their derivatives, including sesamin,
episesamin, sesamolin, sesaminol, sesamol, 7R,7’S-samin and 7R,7’R-samin.
Figure 2. HPLC chromatograms of the transformation of sesamin and sesamolin under treatment
with 2 M sulfuric acid at 60℃ for 0 min (a), 30 min (b), 60 min (c), and the time course study of
relative contents of sesamolin (), sesamol () and 7R,7’S-samin () under treatment with 2 M
sulfuric acid at 60℃ (d). Peak assignment: 1. Sesamin; 2. Sesamolin; 3. 7R,7’S-samin; 4. Sesamol.
The relative content (%) was defined as the peak area ratio of sesamolin, sesamol, or 7R,7’S-samin to
sesamin (n = 3).
Figure 3. HPLC chromatograms of standards of sesamol, sesaminol, sesamin, and sesamolin (a) and
the transformation of sesamin and sesamolin under treatment with conc. sulfuric acid (b) and formic
acid (c) in toluene (1:1, v/v) at 60℃ for 30 min. Peak assignment: 1. Sesamol; 2. Sesaminol; 3.
Sesamin; 4. Sesamolin; 5. 7R,7’S-samin.
Figure 4. HPLC chromatograms of the reaction substrate, sesamin and sesamolin (a), and the
transformation of reaction substrate under treatment with 3 mM potassium permanganate (b), 3 mM
potassium dichromate (c), and 30% hydrogen peroxide (d) in 180 mM sulfuric acid at 60℃ for 30
min. Peak assignment: 1. Sesamin; 2. Sesamolin; 3. Sesamol; 4. 7R,7’S-samin; 5. 7R,7’R-samin.
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Figure 5. HPLC chromatograms of 7R,7’S-samin reacted with 30% hydrogen peroxide (a) and 30%
hydrogen peroxide in 180 mM sulfuric acid (b) at 60℃ for 30 min. Peak assignment: 1.
7
R,7’S-samin; 2. 7R,7’R-samin.
Figure 6. Effect of the concentration of sulfuric acid on the formation of 7R,7’S-samin and 7R,7’R-
samin from sesamolin under treatment with 30% hydrogen peroxide in sulfuric acid (5, 10, 30, 50
mM). Data are mean ± SD (n=3). The relative peak area was defined as the peak area ratio of 7R,
7
’S-samin or 7R, 7’R- samin to sesamin.
Figure 7. Proposed formation mechanisms of 7R,7’S-samin by acid-catalyzed transformation of
sesamolin under general acidic conditions (a) and 7R,7’R-samin by acid-catalyzed transformation of
sesamolin in the presence of hydrogen peroxide (b).
Figure 8. Transformation of sesamolin under general acidic conditions or catalyzed with hydrogen
peroxide under acidic conditions.
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Figure 1.
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Figure 2.
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Figure 3.
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Figure 4.
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Figure 5.
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