640 Letters
pounds 4 and 6 have been reported previously [10–12], while
compounds 3, 5, and 7–10 are reported here for the first time.
The semi-synthetic compounds were purified by semi-prepara-
tive HPLC, while the elucidation of their structures was com-
pleted by means of 1H‑NMR (Supporting Information, Table 1S
and Table 2S), FT-APCI‑MS, FT-APCI‑MS/MS, UV, and IR data and
by comparing the physical and spectroscopic data of each com-
pound with those of compounds 1 and 2.
Semi-Synthesis of Dihydrochalcone
Derivatives and Their in Vitro Anti-
microbial Activities
Maurice D. Awouafack1,2, Souvik Kusari2, Marc Lamshöft2,
Dieudonne Ngamga1, Pierre Tane1, Michael Spiteller2
The in vitro antimicrobial activities of compounds 1–10 are pre-
1
"
Laboratory of Natural Products Chemistry, Department of Chemis-
sented in l Table 1, from which it can be seen that the most po-
try, University of Dschang, Dschang, Cameroon
Institut für Umweltforschung (INFU), Technische Universität Dort-
mund, Dortmund, Germany
tent antimicrobial compounds among those tested were 1–4, 6,
7, and 10. It is also evident that the activities of compounds 1–3,
6, 7, and 10 were quite pronounced on the clinically important
gram-negative bacteria K. pneumoniae and E. coli. The antimicro-
bial efficacies of compounds 1 and 2 against E. coli are compara-
ble to those we reported previously [1]. Interestingly, however,
these six compounds were not active, at the concentration tested,
against the bacteria S. aureus and P. aeruginosa or against the fun-
gal organisms A. niger and C. albicans. The other compounds, viz.
5, 8, and 9, were not active at the concentration tested against
any of the microorganisms (either bacteria or fungi) at our dis-
posal. It was also observed that the potencies of compounds 2,
6, 7, and 10 were higher than those of the other compounds
tested against the clinically relevant K. pneumoniae. On the other
hand, at the concentration tested, compounds 1, 2, 7, and 10
were more active against E. coli than the other compounds tested.
A definite activity profile could be observed, as depicted in
2
Abstract
!
We describe the semi-synthesis of dihydrochalcone derivatives
and their in vitro antimicrobial activities. These compounds were
prepared by modifying two naturally occurring antimicrobial di-
hydrochalcones, erioschalcones A and B, reported by us earlier.
The structures of the compounds were assigned on the basis of
spectroscopic evidence and by comparing their physical and
spectroscopic data with those reported in the literature. All the
compounds were subjected to in vitro antimicrobial assays
against a panel of pathogenic microorganisms, including gram-
positive and gram-negative bacteria, and fungi. The antimicrobial
efficacies of this class of compounds were established by correlat-
ing the activity profile of each compound with its structure and
by comparing the activities of all the compounds with each other
based on their structure. This should enable the development of
other derivatives of the dihydrochalcone family that would serve
as more potent antimicrobial agents against specific pathogens.
"
l Fig. 3, by correlating the differential efficacies of the com-
pounds tested with their structures. It is evidently the prenyl
group present in ring A of 1 and 2 that is responsible for the anti-
microbial efficacies, as has been previously reported [1]. Thus,
the cyclization between the isoprenyl and hydroxy groups leads
to a drastic reduction in activity, as evidenced by the differential
decrease in the activities of 3 (against E. coli) and 4 (against K.
pneumonia). This difference could be explained, in addition to
the organism-specific characteristics, by the position of the ring
formed as a result of the cyclization, which also exposes a hy-
droxy functional group at the 4′ or 2′ positions, respectively. Fur-
thermore, comparing the activities of compounds 3 and 5 re-
vealed that, for antimicrobial activity, a hydroxy group at posi-
tion 4′ must be accompanied by a methoxy group at position 4.
Thus, the positions 4 and 4′ seem to be very prominent in induc-
ing antimicrobial potencies in this class of compound. This is yet
again evidenced by the fact that altering the position of the hy-
droxy group from 4′ to 2′, while keeping the position of the me-
thoxy group constant at position 4, greatly reduces activity, as
could be observed by comparing compounds 4 and 6. Moreover,
comparison of the parent compounds 1 and 2 with compounds
7–10 revealed that the prenyl group at ring A could act as a group
responsible for inducing antimicrobial potencies only when both
the 2′ and 4′ positions (which lie on either side of the group) are
occupied by either hydroxy or methoxy groups. Altering any
group at any of the above positions greatly reduces antimicrobial
activity (e.g., compound 8 having a hydroxy at 2′ and 4′, com-
pound 9 having a hydroxy at 2′ and a methoxy at 4′.
Key words
erioschalcone A · erioschalcone B · dihydrochalcones · antimi-
crobial · semi‑synthesis
Abbreviations
!
TEA:
triethylamine
TFA:
trifluoroacetic acid
TMSH:
trimethylsulfonium hydroxide
Supporting information available online
In connection with our ongoing search for bioactive compounds,
we have carried out the semi-synthesis of compounds 3–10 from
two previously identified naturally occurring antimicrobial dihy-
drochalcones, erioschalcones A (1) and B (2), isolated from Erio-
sema glomerata (Fabaceae) [1]. Dihydrochalcones, which are very
rare from natural plant resources, are claimed to have important
biological activities – mainly antioxidant [2,3], antiplasmodial
[4], antileishmanial [5], and antimicrobial properties [1,2,6,7].
In the present paper, we describe the semi-synthesis of dihydro-
chalcones 3–10 and their preliminary antimicrobial activities.
Cyclizations between the isoprenyl and hydroxy groups of com-
pounds 1 and 2 were carried out with trifluoroacetic acid (TFA)
The results of our study enable us to establish the basic pattern of
action of this class of compounds and will facilitate the develop-
ment of new derivatives of the dihydrochalcone family, which
would serve as more potent antimicrobial agents against specific
pathogens, by substituting various groups at the effective posi-
tions.
"
[8] to yield 3–6 (l Fig. 1). Compounds 1 and 2 were further me-
thylated with trimethylsulfonium hydroxide (TMSH) [9] and trie-
thylamine (TEA, 10% toluene), to yield 7-10 (l Fig. 2). Com-
"
Awouafack MD et al. Semi-Synthesis of Dihydrochalcone… Planta Med 2010; 76: 640–643
Awouafack, Maurice D.
