Hemisynthesis and Spectroscopic Characterization of Three New Chalcone Derivatives from Dorstenia barteri

Article abstract of DOI:10.1007/s10600-017-1962-y

The hemisynthesis of three new chalcones, namely kenzanol, kelianol A, and kelianol B, from Dorstenia barteri (Moraceae) is described here for the first time. The synthetic pathways employed in this work involved the pyrolysis and catalytic hydrogenation of readily available and starting materials, 4-hydroxylonchocarpin and isobavachalcone, two major constituents of the herbaceous plant D. barteri. The structural elucidation of all the compounds was done by mass spectrometry, IR, UV, 1D and 2D NMR analysis, and also by comparison with previous reports.

Full text of DOI:10.1007/s10600-017-1962-y

DOI 10.1007/s10600-017-1962-y
Chemistry of Natural Compounds, Vol. 53, No. 2, March, 2017
HEMISYNTHESIS AND SPECTROSCOPIC CHARACTERIZATION
OF THREE NEW CHALCONE DERIVATIVES FROM Dorstenia barteri
1*
2
2
Bathelemy Ngameni, Ghislain Wabo Fotso, Pantaleon Ambassa,
2
3
2*
Justin Kamga, Arif Dastan, and Bonaventure Tchaleu Ngadjui
The hemisynthesis of three new chalcones, namely kenzanol, kelianol A, and kelianol B, from Dorstenia
barteri (Moraceae) is described here for the first time. The synthetic pathways employed in this work involved
the pyrolysis and catalytic hydrogenation of readily available and starting materials, 4-hydroxylonchocarpin
and isobavachalcone, two major constituents of the herbaceous plant D. barteri. The structural elucidation
of all the compounds was done by mass spectrometry, IR, UV, 1D and 2D NMR analysis, and also by
comparison with previous reports.
Keywords: Dorstenia barteri, Moraceae, 4-hydroxylonchocarpin, isobavachalcone, synthesis.
Chalcones, precursors of flavonoids and isoflavonoids, are present in edible plants, and their derivatives have attracted
increasing attention due to numerous potential pharmacological applications. Natural occurring chalcones as well as synthetic
chalcone analogues have displayed a broad spectrum of pharmacological activities such as cytotoxic [1], antimalarial [2],
antioxidant [3], tyrosinase inhibitory [4], anti-inflammatory [5], cancer chemopreventive [5], and antibacterial [6]. Changes in
their structures have resulted in a high degree of diversity that has been proven useful for the development of new medicinal
agents having improved potency and lesser toxicity. Dorstenia barteri from Moraceae family is recognized to be a particularly
rich source of this type of secondary metabolites [7]. 4-Hydroxylonchocarpin (1) and isobavachalcone (2) are the major
constituents of this plant and the most active in these series [7]. Our previous studies have suggested that certain prenylated
chalcones such as 4-hydroxylonchocarpin (1) and isobavachalcone (2) isolated from D. barteri have very interesting antifungal
activities on Candida albicans and Cryptococcus neoformans [8]. They also showed inhibitory and chemopreventive properties
against matrix metalloproteinase (MMP)-2 secretions from brain tumor-derived U87 glioblastoma cell growth [7, 9]. Our key
starting materials, 4-hydroxylonchocarpin (1) and isobavachalcone (2), were shown to have in vitro activity against P. falciparum
[10]. Recently, Kuete et al. [11] reported that compounds 1 and 2 have potent antimycobacterial, antigonorrheal, and reverse
transcriptase activities. The results from this previous work provided evidence that the crude extract as well as compounds 1
and 2 from D. barteri could be potential sources of a new antimicrobial drug against tuberculosis (TB), gonorrhea, and
probably acquired immunodeficiency syndrome [11]. It has also been observed that the ꢀ,ꢁ-conjugated double bond and the
hydroxyl groups at C-2ꢂ and C-4ꢂ in ring A and at C-4 in ring B were important for enhanced activity. However, little is known
about the modifications of the ꢀ,ꢁ-conjugated double bond, rings A and B of the chalcone skeleton, as well as the role and
influence of substituents at other positions. Furthermore, it is possible that different modifications of the chalcone core may
allow each isomer to define the molecular recognition of its cellular target and to manifest specific biological activity. As part
of our continued interest in both natural or synthetic chalcones, we undertook the thermal and hydrogenation reactions of
4-hydroxylonchocarpin (1) and isobavachalcone (2) under various reaction conditions. The aim of the current synthetic study
was to provide an easy access to prenylated flavonoids at C-3ꢂ with saturated and unsaturated ring B, and ꢀ,ꢁ-positions.
1) Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences,
University of Yaounde I, P. O. Box. 8664, Yaounde, Cameroon, fax: (+237) 242 22 18 73, e-mail: bath_ngameni@yahoo.fr;
2) Department of Organic Chemistry, Faculty of Science, University of Yaounde I, P. O. Box. 812, Yaounde, Cameroon,
fax: (+237) 222 23 53 96, e-mail: ngadjuibt@yahoo.fr; 3) Department of Chemistry, Faculty of Science, Ataturk University, 25240,
Erzurum, Turkey. Published in Khimiya Prirodnykh Soedinenii, No. 2, March–April, 2017, pp. 207–212. Original article
submitted August 2, 2015.
0009-3130/17/5302-0241 02017 Springer Science+Business Media New York
241

TABLE 1. NMR Spectroscopic Data of 1 (CDCl ) and 2 (CD OD) (ꢄ, ppm, J/Hz)
3
3
1
2
C atom
ꢄH
ꢄC
ꢄH
ꢄC
1
2
3
4
5
–
127.4 (s)
131.9 (d)
116.8 (d)
160.3 (s)
116.8 (d)
131.9 (d)
109.8 (s)
161.2 (s)
114.9 (s)
162.0 (s)
108.8 (d)
132.2 (d)
117.9 (d)
145.6 (d)
193.2 (s)
–
–
126.9 (s)
130.8 (d)
117.6 (d)
160.5 (s)
117.6 (d)
130.8 (d)
115.9 (s)
162.6 (s)
113.5 (s)
164.1 (s)
107.2 (d)
129.4 (d)
117.6 (d)
144.3 (d)
192.7 (s)
21.5 (t)
7.78 (d, J = 8.5)
6.91 (br.d, J = 8.5)
7.57 (d, J = 7.9)
6.90 (d, J = 7.9)
–
–
6.91 (d, J = 8.5)
7.78 (br.d, J = 8.5)
6.90 (d, J = 7.9)
7.57 (d, J = 7.9)
6
–
–
–
–
–
–
–
–
1ꢂ
2ꢂ
3ꢂ
4ꢂ
5ꢂ
6ꢂ
ꢀ
6.39 (d, J = 8.9)
8.09 (d, J = 8.9)
7.79 (d, J = 15.3)
7.88 (d, J = 15.3)
–
6.44 (d, J = 8.9)
7.74 (d, J = 8.9)
7.48 (d, J = 15.4)
7.86 (d, J = 15.4)
–
3.50 (d, J = 7.1)
5.33 (br.t, J = 7.1)
–
ꢁ
C=O
1ꢂꢂ
2ꢂꢂ
3ꢂꢂ
4ꢂꢂ
–
–
78.5 (s)
122.6 (d)
126.9 (s)
–
16.9 (q)
25.0 (q)
5.74 (d, J = 10.1)
6.72 (d, J = 10.1)
1.46 (s)
129.2 (d)
116.3 (d)
28.5 (q)
28.5 (q)
–
( )-Me
( )-Me
1.79 (s)
1.86 (s)
Z
E
1.46 (s)
5
OH
OH
OH
1''
5'
O
3
O
O
O
ꢁ
1
a
+
1'
3''
ꢀ
3'
4''
OH
O
OH
O
O
3
4
1
a. ꢅ, 170–200°C, silicon oil, 4 h
Scheme 1. Thermal reaction of natural 4-hydroxylonchocarpin (1).
5
5
OH
OH
OH
1''
O
HO
O
5'
5'
O
HO
3
3
ꢁ
ꢁ
1
1
a
1'
1'
+
3''
ꢀ
ꢀ
3'
3'
3''
4''
1''
OH
OH
O
OH
O
2
5
6
a. ꢅ, 170–200°C, silicon oil, 12 h
Scheme 2. Thermal reaction of natural isobavachalcone (2).
4-Hydroxylonchocarpin (1) and isobavachalcone (2) are abundant metabolites of several species of the genus Dorstenia
[7, 10, 12]. Table 1 shows the spectroscopic data of these metabolites obtained both from the twigs of D. barteri var. multiradiata
[7] and D. barteri var. subtriangularis [10].
To further explore the potential pharmacokinetic properties as well as the structure–activity relationships of variously
modified chalcones, we undertook the transformation of compounds 1 and 2 to their respective derivatives 3–8 under varied
conditions as shown in Schemes 1–3. The thermal reaction of 1 between 170–200ꢃC using a silicon oil bath for 4 h afforded the
corresponding 4-hydroxydihydrolonchocarpin (3) and the cyclized product 4ꢂ- hydroxyisolonchocarpin (4) (Scheme 1) [13, 14],
while the thermal reaction of isobavachalcone (2) at the same temperature and in a silicon oil bath for 12 h yielded dorsmanin A
(5) [15] and ꢁ-hydroxydihydrodorsmanin A, namely kenzanol (6) (Scheme 2). Compounds 3, 4, and 5 are known flavonoids, while
6 is a new compound for which the name kenzanol has been proposed. The mechanism of formation of compounds 3–4 can be
explained firstly by the intramolecular reduction of the double bond Cꢀ–Cꢁ of the chalcone to give the product 3 and, secondly,
the cyclization of the hydroxyl group in C-2ꢂ with the double bond Cꢀ–Cꢁ to form the pyranic cycle C of the flavanone 4.
242

TABLE 2. NMR Spectroscopic Data of 3 (CD OD) and 4 (CDCl ) (ꢄ, ppm, J/Hz)
3
3
3
4
C atom
C atom
ꢄH
ꢄC
ꢄH
ꢄC
1
2
3
4
5
6
–
133.2 (s)
130.5 (d)
116.4 (d)
156.8 (s)
116.4 (d)
130.5 (d)
114.7 (s)
160.9 (s)
110.3 (s)
162.6 (s)
109.4 (d)
132.7 (d)
41.0 (t)
1
2
3a
4
4a
5
6
7
8
8a
–
–
7.05 (d, J = 8.4)
6.68 (d, J = 8.4)
5.49 (dd, J = 12.9, 3.0)
3.07 (dd, J = 16.9, 12.9); 2.79 (dd, J = 16.9, 3.0)
79.8 (d)
43.3 (t)
–
–
–
192.2 (s)
115.2 (s)
130.5 (s)
109.4 (d)
157.6 (s)
110.6 (s)
159.8 (s)
131.0 (s)
129.8 (d)
115.7 (d)
158.1 (s)
115.7 (d)
129.8 (d)
–
6.68 (d, J = 8.4)
7.05 (d, J = 8.4)
7.68 (d, J = 8.7)
6.49 (d, J = 8.7)
–
–
–
–
1
2
3
4
5
6
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
–
–
–
–
6.30 (d, J = 8.9)
7.65 (d, J = 8.9)
3.19 (t, J = 7.5)
2.91 (t, J = 7.5)
–
1
2
3
4
5
6
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
7.36 (d, J = 8.6)
6.86 (d, J = 8.6)
–
6.86 (d, J = 8.6)
7.36 (d, J = 8.6)
–
ꢀ
ꢁ
C=O
30.9 (t)
206.1 (s)
–
–
–
1
2
3
4
ꢂꢂ
ꢂꢂ
ꢂꢂ
ꢂꢂ
ꢂ
78.8 (s)
129.5 (d)
116.7 (d)
28.7 (q)
1
2
3
4
ꢂꢂ
ꢂꢂ
ꢂꢂ
ꢂꢂ
5.65 (d, J = 10.1)
6.66 (d, J = 10.1)
1.46 (s)
–
77.4 (s)
128.1 (d)
116.7(d)
27.2 (q)
26.9 (q)
5.68 (d, J = 10.1)
6.62 (d, J = 10.1)
1.46 (s)
Me2C
Mea
Meb
1.44 (s)
TABLE 3. NMR Spectrocopic Data of 5 (CDCl , ꢄ, ppm, J/Hz)
3
C atom
C atom
ꢄH
ꢄC
ꢄH
ꢄC
1
2
3
4
5
6
–
128.2 (s)
130.9 (d)
116.4 (d)
158.4 (s)
116.4 (d)
130.9 (d)
113.3 (s)
161.2 (s)
109.2 (s)
161.2 (s)
6.40 (d, J = 9.1)
7.71 (d, J = 9.1)
7.47 (d, J = 15.4)
7.85 (d, J = 15.4)
–
109.6 (d)
128.9 (d)
118.5 (d)
144.1 (d)
192.4 (s)
–
76.2 (s)
32.3 (t)
16.8 (t)
27.1 (q)
5ꢂ
6ꢂ
ꢀ
ꢁ
C=O
1ꢂꢂ
2ꢂꢂ
3ꢂꢂ
4ꢂꢂ
Me2C
7.57 (d, J = 8.1)
6.90 (d, J = 8.1)
–
6.90 (d, J = 8.1)
7.57 (d, J = 8.1)
–
–
–
1ꢂ
C-2ꢂ-OH
3ꢂ
13.95 (s)
1.86 (t, J = 6.8)
2.76 (t, J = 6.8)
1.38 (s)
–
–
4ꢂ
In both cases, the products were obtained in moderate yields (see experimental section). It was expected that the reduction of
the double bond Cꢀ–Cꢁ of the chalcone skeleton would be difficult under the above thermal conditions, thus explaining the
low yields.
No study on the thermal reaction of both natural 4-hydroxylonchocarpin (1) and isobavachalcone (2) is reported in
the literature. This is the first report of the thermal reaction of natural 4-hydroxylonchocarpin (1) and isobavahalcone (2).
Kenzanol 6 is reported here for the first time via hemisynthesis by transformation of natural product 2 as a starting material.
The synthesized compounds 3, 4, and 5 have been previously described [13–15]. This is the first time they are being reported
via hemisynthesis under thermal conditions.
Additionally and in order to assess the importance of the double bonds and the ring B of chalcones on their biological
activity, 4-hydroxylonchocarpin (1) was transformed by hydrogenation into the two novel derivatives kelianol A (7) and
kelianol B (8) (Scheme 3).
243

TABLE 4. NMR Spectroscopic Data of 6 and 8 (CDCl , ꢄ, ppm, J/Hz)
3
6
C atom
HMBC
ꢄH
ꢄC
1
2
3
4
5
6
–
127.7 (s)
131.2 (d)
115.6 (d)
156.3 (s)
115.6 (d)
131.2 (d)
113.7 (s)
160.8 (s)
109.2 (s)
160.9 (s)
112.4 (d)
125.8 (d)
44.0 (t)
7.36 (d, J = 8.3)
6.92 (d, J = 8.3)
C-ꢁ, 4
C-2(6), 4
–
–
6.92 (d, J = 8.3)
7.36 (d, J = 8.3)
C-2(6), 4
C-ꢁ, 4
–
–
–
–
–
1ꢂ
13.05 (s)
C-2ꢂ-OH
–
3ꢂ
4ꢂ
5ꢂ
6ꢂ
ꢀa
ꢀb
ꢁ
C=O
1ꢂꢂ
–
6.51 (d, J = 8.8)
7.73 (d, J = 8.8)
3.04 (dd, J = 16.8, 13.2)
2.84 (dd, J = 16.8, 3.1)
5.44 (dd, J = 13.2, 3.1)
–
C-3ꢂ, 1ꢂ, 4ꢂ
C-4ꢂ, C=O
C=O
C=O
C-1
–
44.0 (t)
79.4 (d)
191.4 (s)
-
–
–
–
75.6 (s)
31.8 (t)
16.9 (t)
27.1 (q)
26.4 (q)
–
2ꢂꢂ
3ꢂꢂ
4ꢂꢂ
Mea
Meb
1.79 (t, J = 6.6)
2.68 (t, J = 6.6)
1.37 (s)
C-4ꢂꢂ, 2ꢂꢂ, CMea, CMeb, 3ꢂ
C-2ꢂꢂ, 3ꢂ, 2ꢂ, 4ꢂ
C-3ꢂꢂ; 2ꢂꢂ
1.35 (s)
C-3ꢂꢂ, 2ꢂꢂ
8
C atom
HMBC
ꢄH
ꢄC
1
2
3
4
5
6
1.28 (1H, m)
1.11 (2He, m); 1.61 (2Ha, m)
1.63 (2He, m); 1.80 (2Ha, m)
3.59 (1H, m)
1.63 (2He, m); 1.80 (2Ha, m)
1.11 (2He, m); 1.61 (2Ha, m)
36.9 (d)
31.5 (t)
32.0 (t)
71.4 (d)
32.0 (t)
31.5 (t)
112.5 (s)
163.3 (s)
109.6 (s)
161.0 (s)
109.5 (d)
129.2 (d)
36.0 (t)
35.8 (t)
205.5 (s)
76.1 (s)
32.2 (t)
16.7 (t)
27.1 (q)
27.1 (q)
C-2(6)
C-ꢁ, 1
C-2(6), 1
–
C-2(6), 1
C-ꢁ, 1
–
–
–
–
–
1ꢂ
13.24 (s)
C-2ꢂ-OH
–
–
3ꢂ
4ꢂ
5ꢂ
6ꢂ
ꢀ
ꢁ
C=O
2ꢂꢂ
3ꢂꢂ
6.35 (1H, d, J = 8.9)
7.52 (1H, d, J = 8.9)
2.93 (2H, dt, J = 7.9, 7.7)
1.99 (2H, m)
–
C-4ꢂ
C-4ꢂ, 2ꢂ, C=O
C-ꢁ, 1, C=O
–
–
–
–
1.83 (2H, t, J = 6.8)
2.71 (2H, t, J = 6.8)
1.37 (3H, s)
C-4ꢂꢂ, 2CMe, 2ꢂꢂ
C-3ꢂꢂ, 2ꢂꢂ, 4ꢂ, 2ꢂ
C-2ꢂ, 3ꢂ
4ꢂꢂ
Mea
Meb
1.37 (3H, s)
C-2ꢂ, 3ꢂ
The hydrogenation of the natural 4-hydroxylonchocarpin (1) has not yet been reported in the literature. The resulting
products of our approach, kelianol A (7) and kelianol B (8), were synthesized here for the first time via hemisynthesis from the
1
13
natural product 1 as starting material. Their structures were fully established by H and C NMR, HMQC, and HMBC
experiments (Fig. 1; see Table 4 and experimental section). The two isomers were easily separated by preparative thin-layer
chromatography (see experimental section). Their proton NMR spectra were similar. The only difference is in the chemical
shifts values of H-1 and H-4 protons. In compound 7, these protons appear as two broad singlets at 1.27 and 4.01 ppm,
respectively, suggesting that they are in the equatorial positions, which reduces the 1,3- or 1,5-diaxial interactions [16–19].
244

5
OH
OH
1''
O
5'
O
3
ꢁ
1
a
1'
ꢀ
3''
3'
4''
OH
O
OH
O
1
7, 8
a. H /PtO , EtOH 99%, 0.35 atm., 1 h
2
2
Scheme 3. Hydrogenation of natural 4-hydroxylonchocarpin (1).
OH
H
H
4
OH
O
1
O
H
OH
1
4
O
OH
O
H
8
7
7: 1-Heq, 4-Heq, 4-OHax; trans; 8: 1-Hax, 4-Hax, 4-OHeq; trans
Fig. 1. Proposed structural conformations (chairs I and II) of synthesized trans isomers 7
and 8, respectively [16–19].
This was not the case for the compound 8 where they appeared as two multiplets at 1.28 and 3.59 ppm, respectively, due to
1,3- or 1,5-diaxial steric repulsions [16–19]. Recently, a similar hydrogenation of isobavachalcone (2) was also been reported
by Ngameni et al. [7].
The structures of the natural compounds 1 and 2 and their analogs 3–8 were determined on the basis of spectroscopic
data (UV, IR, MS, 1D and 2D NMR). The purity of the compounds was checked by TLC. The spectral data of all the newly
synthesized compounds were in full agreement with the proposed structures.
In summary, a new hemisynthesized chalcone (6) and their hydrogenated derivatives (7–8) were prepared and fully
characterized using their NMR spectral data. These results make the newly synthesized chalcones and their derivatives interesting
lead molecules for further intermediated synthetic and biological evaluation. Further studies to acquire more information
concerning structure–activity relationships are currently under investigation and in progress in our laboratory.
EXPERIMENTAL
General Procedures. Optical rotation was measured on a PerkinElmer 241 polarimeter. The IR spectra were obtained
on KBr and NaBr disks using a JASCO 302-A spectrophotometer. UV spectra were recorded on a Hitachi UV 3200
spectrophotometer. NMR spectra were recorded on Bruker AMX 300 and AMX 600 MHz NMR spectrometers. ESI-MS
spectra were recorded on a Kratos Concepts IIH mass spectrometer. Precoated silica gel plates (Merck, Kieselgel 60 F-254, 0.5 mm)
were used for PTLC. Thin-layer chromatography (TLC) was performed on silica gel F254 (Merck) precoated aluminum
sheets, and spots were visualized under UV and by spraying with molybdenum solution and heating.
Thermolysis of 4-Hydroxylonchocarpin [(E)-1-(5-Hydroxy-2,2-dimethyl-2H-chromen-6-yl)-3-(4-hydroxyphenyl)-
prop-2-en-1-one] (1). 4-Hydroxylonchocarpin (1) (100 mg) was sealed in a Pyrex tube under reduce pressure and heated in a
silicon oil bath at 170–200ꢃC for 4 h. The tube was then cooled and broken. The solid residue obtained was dissolved in
methanol and chromatographed on a silica gel column and further purified by preparative TLC with a mixture of petroleum
ether and ethyl acetate (7:3) as eluent to give products 3 (8 mg, 8%) and 4 (20 mg, 20%).
4-Hydroxydihydrolonchocarpin [1-(5-Hydroxy-2,2-dimethyl-2H-chromen-6-yl)-3-(4-hydroxyphenyl)propan-
13
1-one] (3) [13]. Yellow oil, C H O . PMR (600 MHz, CD OD, ꢄ, ppm, J/Hz) and C NMR (150 MHz, CD OD), see Table 2.
20 20
4
3
3
+
MS (CI, positive mode), m/z (I , %): 325 ([M + H] , 100), 219 (34), 201 (40), 177 (60), 165 (80). MS (CI, negative mode),
rel
–
m/z (I , %): 323 ([M – H] , 20), 218 (11), 217 (90), 201 (2), 175 (8).
rel
4ꢂ-Hydroxyisolonchocarpin or 2-(4-Hydroxyphenyl)-8,8-dimethyl-2,3-dihydro-4H,8H-pyrano[2,3-f]chromen-
–1
4-one (4) [14]. Yellow crystals, mp 221–222ꢃC, C H O . IR (KBr, , cm ): 3500 (OH), 1675 (C=O), 1595, 1576, 1575,
20 18
4
1515, 1440 (Ar), 1380, 1070 (C–O). UV spectrum (MeOH, ꢆ , nm) (log ꢇ): 231 (3.84), 253 (3.90), 265 (3.94), 309 (3.34).
max
245

13
UV spectrum (MeOH +AlCl ) (log ꢇ): no change. PMR (300 MHz, CD OD, ꢄ, ppm, J/Hz) and C NMR (75 MHz, CD COCD ),
3
3
3
3
+
see Table 2. MS (CI, positive mode), m/z (I , %): 323 ([M + H] , 100), 203 (7). MS (CI, negative mode), m/z (I , %): 321
rel
rel
–
([M – H] , 100), 283 (2), 233 (2), 201 (7), 119 (13).
Thermolysis of (E)-1-(2,4-Dihydroxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (2).
100 mg of isobavachalcone was sealed in a Pyrex tube under reduced pressure and heated in a silicon oil bath between
170–200ꢃC for 12 h. The tube was then cooled and broken. The residue obtained was dissolved in methanol and chromatographed
under successive silica gel columns with a mixture of petroleum ether–ethyl acetate (7:3) as eluent to provide compound 5
(25 mg, 25%) and a newly synthesized product 6 (30 mg, 30%).
Dorsmanin A [(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one] (5) [15].
–1
Yellow oil, C H O . IR (KBr, , cm ): 3682–3445 (OH), 2950, 1650 (C=O), 1600 (C=C), 1540 (Ar). UV spectrum (MeOH,
20 20
4
ꢆ
, nm) (log ꢇ): 208 (4.94), 255 (4.76), 371 (4.87). UV spectrum (MeOH + AlCl , ꢆ , nm) (log ꢇ): 208 (4.94), 386 (4.93),
max
3 max
407 (4.86). UV spectrum (MeOH + AlCl + HCl, ꢆ , nm) (log ꢇ): 209 (4.94), 386 (4.93), 405 (4.80). PMR (300 MHz,
3
max
13
+
CDCl , ꢄ, ppm, J/Hz) and C NMR (75 MHz, CDCl ), see Table 3. MS (CI, positive mode), m/z (I , %): 325 ([M + H] , 100),
323 (25), 269 (4), 149 (2). MS (CI, negative mode), m/z (I , %): 323 ([M – H] , 100), 321 (30), 119 (22).
3
3
rel
–
rel
Kenzanol [1-(2,2-Dimethylchroman-6-yl)-3-hydroxy-3-(4-hydroxyphenyl)propan-1-one] (6). Yellow oil,
25
–1
C H O . [ꢀ] +4.6ꢃ (c 1.00, MeOH). IR (KBr, , cm ): 3682, 3619, 3445 (OH), 3020, 2895, 2401, 2250, 1914, 1521,
20 22
5
D
1470, 1423, 1393, 1333, 1221, 1046, 928, 878, 848, 748, 670, 626. UV spectrum (MeOH, ꢆ , nm) (log ꢇ): 221 (4.58), 281
max
(4.40). UV spectrum (MeOH + AlCl , ꢆ , nm) (log ꢇ): 222 (4.58), 282 (4.39). UV spectrum (MeOH + AlCl + HCl):
3
max
3
no change. UV spectrum (MeOH + NaOAc, ꢆ , nm) (log ꢇ): 222 (4.59), 282 (4.38). UV spectrum (MeOH + NaOMe, ꢆ , nm)
max
max
13
(log ꢇ): 217 (4.62), 242 (4.50), 286 (4.35), 411 (4.13). PMR (300 MHz, CDCl , ꢄ, ppm, J/Hz), C NMR (75 MHz, CDCl ),
and HMBC, see Table 4. MS (CI, positive mode), m/z (I , %): 325 ([M + H – H O] , 100), 323 (50), 321 (5), 267 (3), 221 (21),
165 (11). MS (CI, negative mode), m/z (I , %): 323 ([M – H – H O] , 19), 321 (39), 281 (8), 217 (3).
3
3
+
rel
2
–
rel
2
Hydrogenation of 4 [(E)-1-(5-Hydroxy-2,2-dimethyl-2H-chromen-6-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one (1)]
[20]. Ethanol (99%, 100 mL) and two spatula of platinum oxide (Adamꢂs catalyst) were added to 32 mg of 4-hydroxylonchocarpin
(1) in a 250 mL beaker and the mixture transferred into the PAAR hydrogenation apparatus for 1 h. Then the medium was
filtered under reduce pressure using a Celite gel adsorbent, and the filtrate containing at least two major products on the basis
of the TLC profile was adsorbed and chromatographed using a silica gel column and purified by preparative TLC with a
mixture of petroleum ether and ethyl acetate (17:3) as eluent to afford two new hemisynthesized products, 7 (1.5 mg, 4.7%)
and 8 (6.1 mg, 19.1%).
Kelianol A [trans-1-(2,2-Dimethylchroman-6-yl)-3-(4-hydroxycyclohexyl)propan-1-one] (7); Chair I Isomer.
Colourless oil, C H O . PMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 1.27 (1H, br.s, H-1), 1.37 (6H, s, 2 ꢈ Me), 1.58 (2H, m,
20 28
4
3
H-2, 6e), 1.61 (2H, m, H-2, 6a), 1.67 (2H, m, H-3, 5e), 1.69 (2H, m, H-3, 5a), 1.72 (2H, m, H-ꢁ), 1.84 (2H, t, J = 6.8, H-3ꢂꢂ),
2.72 (2H, t, J = 6.8, H-4ꢂꢂ), 2.94 (2H, dt, J = 7.9, 7.6, H-ꢀ), 4.01 (1H, br.s, H-4), 6.35 (1H, d, J = 8.9, H-5ꢂ), 7.54 (1H, d, J = 8.9,
+
+
H-6ꢂ), 13.27 (1H, s, 2ꢂ-OH). MS (CI, positive mode), m/z (I , %): 333 ([M + H] , 100), 315 ([M + H – H O] , 12), 307 (14),
305 ([M + H – CO] , 3), 279 (2), 231 (6), 229 (2), 69 (4).
rel
2
+
Kelianol B [trans-1-(2,2-Dimethylchroman-6-yl)-3-(4-hydroxycyclohexyl)propan-1-one] (8); Chair II Isomer.
13
Colourless oil, C H O . PMR (300 MHz, CDCl , ꢄ, ppm, J/Hz), C NMR (75 MHz, CDCl ), and HMBC, see Table 4.
20 28
4
3
3
+
+
+
MS (CI, positive mode), m/z (I , %): 333 ([M + H] , 100), 307 (40), 305 ([M + H – CO] , 8), 303 ([M + H – (2 ꢈ CH )] , 5),
rel
3
279 (5), 231 (9), 69 (6).
ACKNOWLEDGMENT
BN and BTN are grateful to the Chemistry Department of the University of Botswana for providing research facilities.
BN and AD are also thankful to the Department of Chemistry, Ataturk University, Turkey for important support with the
experimental equipment.
246

REFERENCES
1.
2.
3.
A. Jurasek, V. Knoppava, M. Dandarova, A. Kovac, and J. Reinprecht, Tetrahedron, 34, 1883 (1978).
G. V. Subbraju, A. R. Nayakulu, and D. Parameshwara, Ind. J. Heterocycl. Chem., 4, 87 (1994).
B. A. Bhat, K. L. Dhar, S. C. Puri, A. K. Saxena, M. Shanmugavel, and G. N. Qazi, Bioorg. Med. Chem. Lett., 15,
3177 (2005).
4.
5.
J. N. Dominguez, C. J. Rodrigues, N. Gamboa de Dominguez, J. Gut, J. Philip, and P. Rosenthal, J. Farmaco, 60,
307 (2005).
N. Yauli, O. Ucuncu, E. Aydin, Y. Gok, A. Yaar, C. Baltaci, N. Yildirim, and M. Kucuk, J. Photochem. Photobiol. A:
Chem., 169, 229 (2005).
6.
7.
S. Khatib, O. Narya, R. Musa, M. Shmuel, S. Tamir, and J. Vaya, Bioorg. Med. Chem., 13, 433 (2005).
B. Ngameni, M. Touaibia, A. Belkaid, P. Ambassa, J. Watchueng, R. Patnam, B. T. Ngadjui, B. Annabi, and R. Roy,
Arkivoc, ix, 91 (2007).
8.
9.
H. N. ElSohly, A. S. Joshi, A. C. Nimrod, L. A. Walker, and A. M. Clark, Planta Med., 67, 87 (2001).
B. Ngameni, M. Touaibia, R. Patnam, A. Belkaid, P. Sonna, B. T. Ngadjui, B. Annabi, and R. Roy, Phytochemistry,
67, 2573 (2006).
10.
B. Ngameni, J. Watchueng, B. F. Fekam, F. Keumedjio, B. T. Ngadjui, J. Gut, M. B. Abegaz, and J. P. Rosenthal,
Arkivoc, xiii, 116 (2007).
11.
12.
13.
14.
15.
16.
17.
V. Kuete, B. Ngameni, A. T. Mbaveng, B. T. Ngadjui, J. J. M. Meyer, and N. Lall, Acta Tropica, 116, 100 (2010).
B. M. Abegaz, B. T. Ngadjui, E. Dongo, and H. Tamboue, Phytochemistry, 49, 1147 (1998).
M. S. Rao, P. S. Rao, B. Balazs, and H. Duddeck, J. Nat. Prod, 61, 1148 (1998).
B. T. Ngadjui, G. W. F. Kapche, H. Tamboue, B. M. Abegaz, and J. D. Connolly, Phytochemistry, 51, 119 (1999).
B. T. Ngadjui, S. F. Kouam, E. Dongo, G. W. F. Kapche, and B. M. Abegaz, Phytochemistry, 55, 915 (2000).
J. March, Advanced Organic Chemistry, 3 Ed., John Wiley & Sons, New York, 1985, 125 pp.
J. Clayden, N. Greeves, S. Warren, and P. Wothers, Organic Chemistry, Oxford University Press, New York,
2001, 456 pp.
rd
18.
19.
20.
F. R. Jensen and C. H. Bushweller, J. Am. Chem. Soc., 88, 4279 (1966).
F. R. Jensen and C. H. Bushweller, J. Am. Chem. Soc., 91, 3223 (1969).
H. Chen, Y. Lin, G. Chen, G. Hu, L. Wang, and L. L. P. Vrijmoed, Chem. Nat. Compd., 42, 407 (2006).
247