Tetrahedron Letters
Concise synthesis of prenylated and geranylated chalcone natural
products by regiospecific iodination and Suzuki coupling reactions
a,
Haomeng Wang a, Zhihong Yan a, Yanan Lei a, Kai Sheng b, Qingwei Yao c, Kui Lu a, , Peng Yu
⇑
⇑
a Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science
& Technology, Tianjin 300457, China
b Tianjin Tianfayuan Agency Center for Environmental Protection Affairs Co. Ltd, Tianjin 300384, China
c Chemo Dynamics, Inc., 3 Crossman Road South, Sayreville, NJ 08872, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Four natural chalcones bearing prenyl or geranyl groups, i.e., isobavachalcone (1), bavachalcone (2), xan-
thoangelol (3), and 20,40,4-trihydroxy-50-geranylchalcone (isoxanthoangelol, 4) were synthesized by using
a regio-selective iodination and the Suzuki coupling reaction as key steps. Among them, the first total
synthesis of 20,40,4-trihydroxy-50-geranylchalcone was achieved in 36% overall yield. Comparing with
the reported methods based on C-alkylation or O-alkylation followed by Claisen rearrangement to intro-
duce the side chain, this new strategy capitalizes on a precious regiochemical control during iodination.
The overall yields for the synthesis of the first three chalcones were improved from 17% to 53%, 12% to
35%, and 28% to 50%, respectively.
Received 11 October 2013
Revised 1 December 2013
Accepted 10 December 2013
Available online 19 December 2013
Keywords:
Chalcones
Regiospecific
Iodination
Ó 2013 Elsevier Ltd. All rights reserved.
Suzuki coupling reaction
Introduction
subsequently finished the total synthesis of 1, 2, and 3 with
17.2%, 12.4%, and 28.1% overall yield, respectively.11 Both of these
Chalcones containing prenyl or geranyl groups are an abundant
subclass of flavonoids widely found in nature and display a variety
of biological and pharmacological activities. Isobavachalcone (1),
first isolated from Psoralea corylifolia,1a showed antibacterial, anti-
fungal, anticancer, anti-reverse transcriptase, antitubercular, and
antioxidant activities;1–3 Bavachalcone (2), also isolated from
Psoralea corylifolia,1a,4a, was shown to display a significant inhibi-
tory effect on baculovirus-expressed BACE-1 in vitro4b as well as
inhibition on osteoclast differentiation.4c This natural chalcone also
syntheses used O-alkylation followed by Claisen rearrangement as
key steps to introduce the prenyl or geranyl groups and poor regio-
selectivity of the latter process was found to be the main reason for
the low overall yield. Recently McGlinchey applied iodination and
OH
OH
HO
OH
HO
exhibits extremely high a
-glucosidase inhibitory activity.5 Xantho-
angelol (3), isolated from fresh roots of A. keiskei,6 exhibits antibac-
terial activity against Gram-positive pathogenic bacteria7
antitumor-promoting activity and cytotoxicity against neuroblas-
toma cells;8 The newly discovered compound 4, 20,40,4-trihy-
droxy-50-geranylchalcone and coined here as isoxanthoangelol,
which was isolated from the leaves of Artocarpus communis, was
reported to possess anticancer activity in SW 872 human liposar-
coma cells (Fig. 1).9 Due to their structural uniqueness and potent
bioactivity, the synthesis of prenylated or geranylated chalcone
natural products has attracted much attention in recent years. In
2010, Jung reported the first total synthesis of 3 with a total yield
of 16.8% starting from 2,4-dihydroxyacetophenone.10 Sugamoto
O
OH
O
2
1
Bavachalcone
Isobavachalcone
OH
OH
HO
HO
OH
OH
O
4
O
3
2',4',4-trihydroxy-5'-geranylchalcone
(Isoxanthoangelol)
Xanthoangelol
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Corresponding authors. Tel.: +86 22 60601268; fax: +86 22 60602298.
Figure 1. Selected chalcones containing prenyl or geranyl groups.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.