Tetrahedron Letters 51 (2010) 495–498
Tetrahedron Letters
An efficient synthesis of (± ±)-pnꢀduptin A pnꢀ (± ±)iso-pnꢀduptin A, inhibitous
of ꢀengde)2 viupl pctivity
a
a
b
a,*
Chin Fei Chee , Iskandar Abdullah , Michael J. C. Buckle , Noorsaadah Abd Rahman
a
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
Department of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Panduratin A and its regioisomer isopanduratin A are synthesized in four steps from (E)-ocimene, [(E)-
,7-dimethyl-1,3,6-octatriene] via a Diels–Alder cycloaddition reaction.
Received 3 September 2009
Revised 2 November 2009
Accepted 9 November 2009
Available online 12 November 2009
3
Ó 2009 Elsevier Ltd. All rights reserved.
Panduratin A and its regioisomer isopanduratin A are cyclohex-
enyl chalcone natural products that show a wide spectrum of bio-
logical activity. It has recently been reported that panduratin A
Following the conditions described in Table 1, entry 7, com-
pounds 4, 6–8 and their regioisomers 4p, 6p, 7p and 8p were pre-
pared in excellent yields and no polymerization of the diene
(described as a complex mixture in Table 1) was observed. The
products were isolated in a 3:2 para/meta ratio and the structure
of the major product (the para isomer) for each reaction is given
in Table 2.
The Diels–Alder reaction (Table 2, entry c) was first carried out
under the same reaction conditions as those of entry 7 (Table 1)
where excess ocimene was used and the reaction mixture was
heated at 120 °C in a pressure tube. However, no Diels–Alder ad-
duct was isolated even after the reaction was left for 24 h. The iso-
lated product indicated polymerization of ocimene instead. The
use of various Lewis acids to catalyze the reaction also resulted
in polymerization of the acid-sensitive terminal conjugated double
bond in ocimene.
1
and hydroxypanduratin A (Fig. 1), isolated from Boesenbergia rotun-
da (L.) showed good inhibitory activities towards dengue-2 virus
2
NS3 protease with K
i
values of 25 and 21
l
M, respectively. While
a number of syntheses of cyclohexenyl chalcones have been de-
3
scribed, surprisingly the synthesis of panduratin A has never been
reported. Herein, we report an efficient method for the synthesis of
(
±)-panduratin A and (±)-isopanduratin A through Diels–Alder
0
0
0
cyclization of 2 -hydroxy-4 -methoxy-6 -ethoxymethoxychalcone
and (E)-ocimene.
0
0
0
Our studies began with model reactions between 2 ,4 ,6 -tri-
hydroxychalcone 1 and 2,3-dimethyl-1,3-butadiene, carried out
in various solvents as well as without solvent. Heating the two
compounds for an extended period of time at 110 °C resulted in
the formation of 5,7-dihydroxyflavanone (Table 1). The use of Le-
Ocimene can exist in the E- or Z-configuration in nature
(Scheme 1). When pure (Z)-ocimene was reacted with chalcone
2, no Diels–Alder adduct was isolated. Instead, polymerization of
the ocimene was observed. However, when a mixture of (E)- and
wis acid catalysts such as BF
sulted in extensive polymerization of the diene.
The reaction was also carried out with 2 ,4 ,6 -trimethoxychal-
cone 2 (as the dienophile) and 2,3-dimethyl-1,3-butadiene. Initial
reaction (Table 1, entry 5) performed at room temperature with
3
ꢀEt
2 3 2
O, AlCl and ZnCl , however, re-
0
0
0
1
equiv of diene in dry toluene gave no product even after 30 h
of stirring. Increasing the equivalence of diene also resulted in a
similar observation. When the reactants were placed in a pressure
tube and heated at 50 °C for 18 h, a small amount of the expected
product was obtained (Table 1, entry 6). However, increasing the
temperature to 120 °C and stirring overnight in a pressure tube re-
sulted in the Diels–Alder adduct 5 being isolated in 93% yield
OH
R
Me
O
(Table 1, entry 7).
OH
Me
Me
R = OMe : panduratin A
R = OH : hydroxypanduratin A
*
Figdue 1. Panduratin A and hydroxypanduratin A.
Chee, Chin Fei
