LETTER
2469
Synthesis of Harounoside, A Naturally Occurring Pentalongin Hydroquinone
Bisglucoside
a
a
a
b
a
S
T
ynthesis of
H
a
u
rounoside yen Nguyen Van, Sven Claessens, Pascal Habonimana, Kourosch Abbaspour Tehrani, Luc Van Puyvelde,
a
Norbert De Kimpe*
a
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
b
Department of Organic Chemistry, Faculty of Science, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Fax +32(9)2646243; E-mail: norbert.dekimpe@UGent.be
Received 29 June 2006
In continuation of our synthetic efforts towards physio-
logically active pentalongin derivatives,6 we now report
the first synthesis of the natural product harounoside 2.
Abstract: The recently isolated natural product harounoside,
namely 5,10-dihydroxy-2H-naphtho[2,3-c]pyran-b-D-bisglucopyr-
anoside, was conveniently synthesized for the first time from penta-
longin in 84% yield over three steps.
–9
Concerning the synthesis of arylglucosides and naturally
occurring glycosides, various glucosylation methods have
been developed since the classical Koenigs–Knorr syn-
thesis.10 These procedures usually require an activated
glucosyl donor, such as glucosyl halides.1 However, it
has been shown that the reaction of per(O-acetyl)glucosyl
bromide with an aglycone in the presence of various silver
salts as promoter, often led to a complex mixture of
Key words: natural products, total synthesis, glucosidation
1,12
Mitracarpus scaber Zucc. is an annual plant used in Afri-
can traditional medicine for its antifungal and antiparasit-
1
ic activities. Recently, a new pentalongin hydroquinone
bisglucoside, named harounoside 2, has been isolated
1
3
2
reaction products. The directed glucosylation of hydro-
quinone with penta-O-acetylglucose in the presence of
one equivalent of BF ·OEt in dichloromethane has been
from this plant (Figure 1). Salient structural features of
harounoside are the reduced pentalongin structure and the
bisglucoside unit with b-stereochemistry. The natural
product pentalongin 1, which showed pronounced anti-
fungal and antiparasitic activities, has been isolated from
the roots of Pentas longiflora Oliv. (Rubiacea).3 The
powder of the roots of P. longiflora is used by traditional
healers in the dispensary of traditional medicine of Cur-
phametra (Butare, Rwanda) to treat the skin disease pityr-
3
2
shown to be a convenient method to obtain tetra-O-acetyl-
14
b-D-glucopyranosides of hydroquinone. Unfortunately,
in our hands, this procedure completely failed with the
hydroquinone derived from pentalongin 6, resulting in a
complex mixture of reaction products. Recently, the imi-
–5
15
date methodology has been shown as a good method for
the synthesis of naturally occurring b-glycosides in the
presence of Lewis acid catalysis, as exemplified for 7-hy-
4
iasis versicolor. All these physiological activities of
pentalongin and its reduced form underline the impor-
tance of this class of natural products as a potential drug
candidate.
1
6
droxycoumarin glucuronosides and retinoic acid gluco-
conjugates.17 We have applied this methodology to the
synthesis of harounoside 2 because of the mild reaction
conditions (cf. the enol ether moiety in the structure) and
the fact that the reaction product could be selectively
HO
OH
OH
O
O
16,17
directed towards the desired b-isomer.
HO
The hemiacetal 4 has been obtained by selective deacety-
O
O
lation of 1,2,3,4,6-pentaacetyl-D-glucose (3) in various
ways.1
7–19
The 1-O-acetyl group was removed by
O
OH
treatment of 1,2,3,4,6-pentaacetyl-D-glucose (3) with
hydrazinium acetate in dimethyl formamide at room
HO
HO
O
O
O
18
temperature (Scheme 1), giving rise to hemiacetal 4
19
OH
2 (harounoside)
(a/b, 5:1, measured by NMR spectroscopy ) in 99%
yield.
1
(pentalongin)
Treatment of compound 4 with trichloroacetonitrile14 in
the presence of DBU in dichloromethane at room temper-
ature afforded the corresponding trichloroacetimidate 5 in
Figure 1
8
5% yield (Scheme 1).14 O-(2,3,4,6-Tetra-O-acetyl-a-D-
glucopyranosyl)trichloroacetimidate (5) was obtained as
the a-isomer as indicated by the typical acetal carbon sig-
13
nal at 92.6 ppm in the C NMR spectrum and the doublet
SYNLETT 2006, No. 15, pp 2469–2471
Advanced online publication: 08.09.2006
1
8
.0
9
.2
0
0
6
1
of the acetal hydrogen at 6.56 ppm (J = 3.9 Hz) in the H
DOI: 10.1055/s-2006-950437; Art ID: G19706ST
NMR spectrum. The configuration of the anomeric carbon
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Georg Thieme Verlag Stuttgart · New York