Synthesis and biological activity of isoamoenylin, a metabolite of Dendrobium amoenum

Article abstract of DOI:10.1271/bbb.66.2236

Isoamoenylin (6), a dihydrostilbene from Dendrobium amoenum, was synthesised from 3,4,5-trimetho-xybenzaldehyde (1) in four steps with an overall yield of 60%. The spectral data for synthetic 6 are in good agreement with those of the natural product. Isoamoenylin showed moderate antioxidative and weak antibacterial activities.

Full text of DOI:10.1271/bbb.66.2236

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Synthesis and Biological Activity of Isoamoenylin, a
Metabolite of Dendrobium amoenum
Somepalli VENKATESWARLUa, Mudunuri S. S. RAJUa & Gottumukkala V. SUBBARAJUa
a Laila Impex R & D Centre, Unit I, Phase III Jawahar Autonagar, Vijayawada 520 007,
India
Published online: 22 May 2014.
To cite this article: Somepalli VENKATESWARLU, Mudunuri S. S. RAJU & Gottumukkala V. SUBBARAJU (2002) Synthesis and
Biological Activity of Isoamoenylin, a Metabolite of Dendrobium amoenum , Bioscience, Biotechnology, and Biochemistry,
66:10, 2236-2238, DOI: 10.1271/bbb.66.2236
To link to this article: http://dx.doi.org/10.1271/bbb.66.2236
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Biosci. Biotechnol. Biochem., 66 (10), 2236–2238, 2002
Note
Synthesis and Biological Activity of Isoamoenylin,
a Metabolite of Dendrobium amoenum†
††
Somepalli VENKATESWARLU, Mudunuri S. S. RAJU, and Gottumukkala V. SUBBARAJU
Laila Impex R & D Centre, Unit I, Phase III, Jawahar Autonagar, Vijayawada 520 007, India
Received March 22, 2002; Accepted May 20, 2002
Isoamoenylin (6), a dihydrostilbene from Dendrobi-
um amoenum, was synthesised from 3,4,5-trimetho-
xybenzaldehyde (1) in four steps with an overall yield of
min C (IC50: 852
m
M
) and BHA (butylated hydrox-
).
yanisole; IC50: 967
m
M
The antibacterial activity of 6 was determined by
the agar cup-plate diŠusion method.12) The zone of
inhibition (diameter in mm) at a concentration of
60
%. The spectral data for synthetic 6 are in good
agreement with those of the natural product. Isoamo-
enylin showed moderate antioxidative and weak an-
tibacterial activities.
200 mg ml against Pseudomonas aeruginosa (Gram
W
„ve), Escherichia coli (Gram „ve), Bacillus subtilis
(Gram +ve), and Staphyllus aures (Gram +ve), was
8.5, 9.0, 8.5 and 8.5 mm, respectively. 5 did not show
any appreciable antibacterial activity. These com-
pounds did not show any signiˆcant antifungal activ-
Key words: isoamoenylin;
3-[2-(3,4,5-trimethoxy-
phenyl)ethyl]phenol; Dendrobium amoe-
num; antioxidative activity
ity against Aspergillus wentii or Aspergillus niger
even at a 500 g ml concentration.
,
Dihydrostilbenes,
a
small group of natural
m
W
products, have been found to exhibit various biologi-
cal activities such as antimitotic1,2) and endogenous
growth regulatory.3,4) Isoamoenylin 6, a dihydrostil-
bene has been recently isolated from the orchid,
Dendrobium amoenum5) as a new natural product.
As a part of our synthetic studies on phenolics,6,7) we
synthesised isoamoenylin for the ˆrst time and the
results are reported in this note.
Experimental
General. All solvents were dried and distilled be-
fore use, and all reagents were procured from com-
mercial sources and used without puriˆcation. Melt-
ing point (mp) data were recorded by a V Scientiˆc
melting point apparatus in open capillaries and are
Sodium borohydride reduction of 3,4,5-trimethox-
ybenzaldehyde (1) in methanol gave the 3,4,5-
trimethoxybenzyl alcohol (2) in a quantitative yield.
Phosphonate ester 3 was prepared from 2 by treating
with phosphorous tribromide and then by triethyl
uncorrected. UV spectra were recorded by a
Shimadzu UV-190 spectrophotometer, IR spectra by
a Perkin-Elmer BX1 FTIR spectrophotometer, and
mass spectra by a VG micromass 70–70H mass spec-
trometer. dH NMR (400 MHz) spectra were recorded
by a Varian Gemini 400 MHz NMR spectrometer,
phosphite in an 82z yield. A Wittig-Hornor reaction
of 3 with 3-benzyloxybenzaldehyde (4), which had
been prepared from 3-hydroxybenzaldehyde, in the
presence of sodium hydride furnished trans-stilbene 5
the value for chemical shifts (
and coupling constants ( ) in Hertz (Hz). The fol-
lowing abbreviations are used to describe peak
patterns when appropriate: br broad, s singlet,
＝
d doublet, t triplet, q quartet, m multiplet. All
d) being given in ppm
J
in an 80
z
yield. Hydrogenation of 5 over palladium-
yield (scheme 1). The spec-
＝
＝
＝
＝
＝
charcoal gave 6 in a 93
z
tral data for synthetic 6 agree well with those of
natural 6. Thus, 6 was obtained by starting from 1 in
reactions were carried out in an argon atmosphere,
except for the hydrogenation reaction. Acme silica
gel G and silica gel (100–200 mesh) were used for ana-
lytical TLC and column chromatography, respec-
tively.
four steps with an overall yield of 60z.
In view of the structural similarity of 6 with natur-
al antioxidants,8,9) we screened 6 and its precursor 5
for their antioxidative activity by the nitro blue
tetrazolium (NBT) method.10,11) 5 and 6 showed
moderate superoxide-scavenging activity (IC50: 133
3,4,5-trimethoxybenzyl alcohol (2). To an ice
cold solution of 3,4,5-trimethoxybenzaldehyde (5 g,
25.5 mmol) in methanol (50 ml) was added in small
portions sodium borohydride (1.5 g, 38 mmol), and
and 694
m , respectively) compared to the other
M
known antioxidants, vitamin E (IC50: 728
mM), vita-
†
Laila Impex Communication
#
17
††
To whom correspondence should be addressed. Tel: +91-866-541303; Fax: +91-866-475278; E-mail: subbaraju
＠
nettlinx.com
Abbreviations: NBT, nitro blue tetrazolium; BHA, butylated hydroxyanisole; THF, tetrahydrofuran; NaCN, sodium cyanide; EDTA,
ethylenediaminetetraacetic acid

Synthesis and Biological Activity of Isoamoenylin
2237
Scheme 1. Reagents and conditions: (i) NaBH4, MeOH, 1 h, 99
z
; (ii) PBr3, THF-benzene, rt, 2 h, triethyl phosphite, 140–1509C, 3 h,
82
z
; (iii) NaH, THF, rt, 4 h, 80
z
; (iv) H2, Pd-C, MeOH, rt, 2 h, 93z.
the mixture was stirred for 1 h at rt. Methanol was
distilled oŠ under vacuum, and the product diluted
with cold water. After acidiˆcation with dil. HCl, the
solution was extracted with chloroform. The chlo-
roform layer was successively washed with water,
column with petroleum ether-EtOAc (1:1) as the
eluent to give 3 (6.5 g, 82 ) as an oil.
z
3-Benzyloxybenzaldehyde (4). A mixture of 3-
hydroxybenzaldehyde (1.5 g, 12.3 mmol), benzyl
bromide (1.8 ml, 15 mmol), potassium carbonate
(3.4 g, 25 mmol) and acetone (25 ml) was heated un-
der re‰ux for 2 h. After completing the reaction, the
solid was ˆltered oŠ and the solvent was evaporated.
The residue obtained was chromatographed in a
silica gel column with a mixture of petroleum ether
and ethyl acetate (95:5) as the eluent to give 4 (2.2 g,
10
z
sodium bicarbonate and brine, and dried over
sodium sulfate. The residue obtained after evapora-
tion of the solvent was chromatographed in a silica
gel column with petroleum ether-EtOAc (80:20) as
the eluent to give 2 (5 g, 99
max (neat) cm„1: 3407, 1594, 1506, 1237, 1127, 1006,
828, 774.
z
) as an oil (lit.13) oil). IR
n
85
z 9 9
), mp 52–54 ); IR nmax (neat)
(lit.14) mp 51–52
Diethyl 3,4,5-trimethoxybenzyl phosphonate (
3
).
cm„1: 1696, 1590, 1386, 1260, 1026, 772.
Alcohol 2 (5 g, 25.3 mmol) in THF (5 ml) and ben-
zene (15 ml) was treated with a solution of phos-
phorous tribromide (3.2 ml, 33 mmol) in THF (1 ml)
1-(3-Benzyloxyphenyl)-2-(3,4,5-trimethoxyphenyl)
ethylene (5). To an ice-cooled solution of sodium
and benzene (5 ml) while stirring at 0
9
C. The reaction
hydride (0.38 g, 8 mmol) in THF (10 ml) was slowly
added phosphonate ester 3 (2.1 g, 6.6 mmol) in THF
(5 ml) over 15 min. The solution temperature was al-
lowed to rise to rt, and the mixture stirred for 15 min.
mixture was allowed to warm to room temperature
and left to stand for 2 h. The reaction mixture was
then poured into ice-cooled water, and the product
was extracted three times with ether. The combined
ethereal extract was washed with brine, dried over
Na2SO4, and the solvent was evaporated. The crude
product obtained was heated with triethyl phosphite
(6.5 ml, 40 mmol) at 140–150 C for 3 h. The excess
9
triethyl phosphite was removed under vacuum, and
the residue was chromatographed in a silica gel
After cooling the solution to 59C, 3-benzyloxyben-
zaldehyde (4.1 g, 4.7 mmol) in THF (5 ml) was
added, and the mixture stirred at the same tempera-
ture for 2 h and then at rt for a further 2 h. Methanol
(2 ml) was added to the reaction mixture to destroy
the excess sodium hydride, before it was diluted with
ice-cooled water and acidiˆed with dil. HCl. The

2238
S. VENKATESWARLU et al.
acidic solution was extracted with chloroform, and
the organic layer was successively washed with water,
for encouragement. We also thank Mr. A. V.
Krishnaraju and Mrs. R. Jayalakshmi for providing
biological activity data.
10
z
sodium bicarbonate and brine, and ˆnally dried
over sodium sulfate. The residue obtained was chro-
matographed in a silica gel column with a mixture of
petroleum ether and ethyl acetate (90:10) as the
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Acknowledgments
We thank Sri G. Ganga Raju, Chairman, and Mr.
G. Rama Raju, Managing Director, of Laila Impex