122
Chem. Pharm. Bull. 63, 122–125 (2015)
Vol. 63, No. 2
Note
Attempt to Synthesize 2,3,5,4ꢀ-Tetrahydroxystilbene Derived from
2,3,5,4ꢀ-Tetrahydroxystilbene-2-O-β-glucoside (THSG)
,a
,a
Masafumi Tamura,* Yuhei Koshibe,a Kiho Kaji,a Jun-ya Ueda,b and Yoshiaki Shirataki*
a Faculty of Pharmaceutical Sciences, Josai University; 1–1 Keyakidai Sakado, Saitama 350–0295, Japan: and
b Frontier Research Core for Life Sciences, University of Toyama; 2630 Sugitani, Toyama 930–0194, Japan.
Received September 1, 2014; accepted November 24, 2014; advance publication released online December 4, 2014
An attempt to synthesize aglycone 1 derived from 2,3,5,4ꢀ-tetrahydroxystilbene-2-O-β-glucoside (THSG)
via the Wittig reaction and Mizoroki–Heck reaction is described. In the Wittig protocol, 2,3,5,4ꢀ-tetra-
methoxystilbene 2 was obtained. Additionally, a palladium-catalyzed Mizoroki–Heck reaction strategy
yielded 2-aryl-2,3-dihydrobenzofuran 13 instead of derivative 12 in good yield.
Key words Polygonum multiflorum; Mizoroki–Heck reaction; 2-aryl-2,3-dihydrobenzofuran; 2,3,5,4′-
tetrahydroxystilbene-2-O-β-glucoside (THSG)
Dietary polyphenols, such as flavonoids,1) stilbenes2) and ity upon exposure to irradiation and oxygen or at a particular
lignans,3) are now recognized for their beneficial uses in pH and temperature.19,20)
human health care, such as in the treatment and prevention of
The bioactivities of polyhydroxy stilbene compounds have
cardiovascular diseases. Cancer prevention has also been asso- mainly been attributed to their antioxidant property, which is
ciated with consumption of a diet rich in these polyphenols.4,5) related to the position of hydroxyl groups.2,10)
In particular, resveratrol (3,5,4′-trihydroxy-trans stilbene),
In addition, polyhydroxy stilbenes with catechol substitu-
a polyphenolic natural product present as a glycoside6) or ents dramatically increase antioxidative activity, but the gly-
methoxide,7) has chemoprevention effects against cardiovas- cosylation of stilbene reduces their activity compared to the
cular diseases,8) cancer,9) Alzheimer’s disease and aging10,11) corresponding aglycone.6,21,22)
(Fig. 1).
Therefore, the aglycone 1 (2,3,5,4′-tetrahydroxystilbene)
However, the therapeutic potential of resveratrol is limited from THSG is a useful antioxidant and free radical scavenger
because free resveratrol is rapidly absorbed in the upper GI and possesses potential therapeutic application to human dis-
tract following oral dosing, quickly metabolized to glucuro- ease.
nides and sulfates and quickly cleared from the circulation.12)
To the best of our knowledge, the aglycone 1 derived from
2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is THSG has rarely been reported on in the literature, and
also a polyphenolic glycoside extracted from the dried root only two reports mention antioxidative activities. Reports
tuber of Polygonum multiflorum (Fig. 1).
indicate that aglycone 1 has very high 1,1-diphenyl-2-picryl-
The dried root tuber of Polygonum multiflorum (Radix hydrazyl (DPPH) radical scavenging activity (IC50=0.38µM)
Polygoni mutiflori), a traditional herbal drugs in the Chinese in vitro, which is nearly a hundred times that of THSG
pharmacopeia, has been used as an important health protec- (IC50=40µM).23,24)
tive agent and nutritional supplement for thousands of years.13)
Our interest in the aglycone 1 stemmed from its high anti-
Recent pharmacological studies indicated that THSG has oxidative activity, therapeutic potential and novel mechanism
strong antioxidative and free radical scavenging activity.14–16) of action. However, the systematic investigation of biological
In addition, THSG is able to reduce hyperlipidemia, prevent and therapeutic properties of the aglycone 1 is somewhat lim-
lipid peroxidation, and protect the cardiovascular system.17) It ited by its general accessibility. Besides methods of aglycone
is also effective in the prophylaxis and therapeutic treatment 1 extraction from plants, efficient methods of aglycone 1 syn-
of Alzheimer’s disease.18)
thesis would be highly desirable.
The usefulness of THSG, however, is limited by its instabil-
Fig. 1. Chemical Structure 2,3,5,4′-Tetrahydroxystilbene (1) THSG and Resveratrol
*To whom correspondence should be addressed. e-mail: tamuraty@josai.ac.jp; tshira@josai.ac.jp
© 2015 The Pharmaceutical Society of Japan