A concise synthesis of the DNA-intercalating and antimalarial alkaloid cryptolepine and its fluorescence behaviour in solvents of different polarities

Article abstract of DOI:10.1002/hlca.200890212

A microwave-induced rapid and facile synthesis of the DNA-intercalating and antimalarial drug cryptolepine is described. The key step in this synthesis involves the aqueous-phase base-catalyzed condensation of isatin and 1-acetyl-1H-indol-3-yl acetate which has been simplified and expedited by dielectric heating, employing an ordinary domestic microwave oven. The method transforms the synthesis of an important drug molecule from a prohibitively lengthy process to a matter of a few minutes with a much improved yield. Dual absorption and fluorescence is observed from the molecular system in solvents of different polarity thus providing valuable insight into its binding modes toward protein or DNA.

Full text of DOI:10.1002/hlca.200890212

Helvetica Chimica Acta – Vol. 91 (2008)
1975
A Concise Synthesis of the DNA-Intercalating and Antimalarial Alkaloid
Cryptolepine and Its Fluorescence Behaviour in Solvents of Different
Polarities
a
a
a
b
by Tapan Kumar Lai ), Asima Chatterjee† ), Julie Banerji* ), Deboleena Sarkar ), and
b
Nitin Chattopadhyay )
a) UGC-Centre of Advanced Studies on Natural Products Including Organic Synthesis, Department of
Chemistry, The University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India
(
e-mail: juliebanerji@gmail.com)
b) Department of Chemistry, Jadavpur University, Jadavpur, Kolkata-700032, India
A microwave-induced rapid and facile synthesis of the DNA-intercalating and antimalarial drug
cryptolepine is described. The key step in this synthesis involves the aqueous-phase base-catalyzed
condensation of isatin and 1-acetyl-1H-indol-3-yl acetate which has been simplified and expedited by
dielectric heating, employing an ordinary domestic microwave oven. The method transforms the
synthesis of an important drug molecule from a prohibitively lengthy process to a matter of a few minutes
with a much improved yield. Dual absorption and fluorescence is observed from the molecular system in
solvents of different polarity thus providing valuable insight into its binding modes toward protein or
DNA.
1. Introduction. – Malaria is one of the planetꢀs deadliest diseases and a leading
cause of sickness and death in the developing world. It kills over a million people each
year – mostly children, with an estimated 300 – 500 million clinical cases per year and
some 3.2 billion people living in 107 countries or territories are at risk. Africa alone
accounts for over 90% of reported cases [1]. Cryptolepine (5-methyl-5H-indolo[3,2-
b]quinoline; 1), found in the decoction of the roots of the West African climbing shrubs
Cryptolepis sanguinolenta and Cryptolepis triangularis N. E. Br. (Periplocaceae), is a
rare example of a natural product whose synthesis was reported prior to its isolation
[
2]. Pharmacological investigations on cryptolepine and its analogues have revealed
diverse biological activities of this polyheteroaromatic alkaloid that include its DNA-
intercalating, cytotoxic, hypotensive, antipyretic, anti-inflammatory, antibacterial, and
antihyperglycemic activities in addition to its more celebrated role in the control of
various forms of malaria [3 – 8]. The skeleton also serves as a template for the
development of newer antimalarials so urgently required to combat the growing
menace of malaria caused by various resistant strains of the parasite Plasmodium
falciperum. The interest in this polyheteroaromatic skeleton has grown further after the
discovery of the antitumour activity of ellipticine and 9-methoxyellipticine [9]. Since
natural sources are not sufficient to satisfy the ever-growing demand of this wonder
alkaloid, an explosion of activities toward the construction of the cryptolepine skeleton
is obvious. After the first synthesis of Fichter and Boehringer in 1906 [10], several
attempts to synthesize this skeleton were made over the decades [11 – 15]. All these
ꢁ
2008 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 91 (2008)
methods involve poorly available starting materials and multi-step procedures
demanding large amounts of time and energy, often requiring the use of high pressure
vessels and drastic conditions sometimes leading to decomposition.
Isatin (2) is a versatile molecule, upon which the synthesis of a large number of
bioactive heterocycles, spiroheterocycles, and metal complexes is based [16 – 18]. Ever
since the introduction by Gedye et al. and Giguere et al. [19], microwaves have been
extensively utilized to drive organic reactions, thus saving time and energy and
providing eco-friendly methods for many reactions [20]. In conjunction with our earlier
efforts of simplifying lengthy procedures for synthesis of bioactive heterocycles with
the help of microwaves [21 – 24], and studies on bioactive natural components [25], we
report herein a microwave mediated efficient synthesis of cryptolepine starting from
readily available materials, anthranilic acid and isatin.
Absorption and fluorescence spectroscopic techniques serve as useful tools for
monitoring the different modes of binding of various drugs to protein and DNA
[
26][27]. The polarity of solvents often modified these spectral parameters [27][28].
Although cryptolepine has been used extensively for studying the intercalative mode of
binding [29], its intrinsic fluorescence behaviour has not been reported. Here we
studied the fluorescence characteristics of cryptolepine and observed an interesting
solvent-polarity dependent two-species spectroscopic behaviour in various common
solvents. These observations are helpful in exploring its binding mode toward proteins
or DNA and may offer useful insight while tuning its efficacy as a drug.
2
. Results and Discussion. – 2.1. Synthesis of Cryptolepine. All the microwave-
promoted steps described in this work were rapid, needing only a few minutes for
completion of the reactions that usually take hours, even days to carry out a single step
[
30]. In most of the cases, conversions were almost complete within the irradiator itself,
and pure products were obtained from the reaction mixtures by a simple crystallization
step thus further simplifying the purification procedure. The protocol has been divided
into two parts: a) a simple synthesis of 1-acetyl-1H-indol-3-yl acetate (3), and b) the
synthesis of cryptolepine (1) through an aqueous-phase microwave-promoted con-
densation of 3 and 2 (Schemes 1 and 2). The synthesis is now so facile that starting from
isatin and anthranilic acid, cryptolepine could be obtained in a single day.
In Scheme 1, the condensation between the sodium salts of anthranilic acid (4), and
chloroacetic acid (5), in aqueous solution under microwaves is shown. This yielded off-
white crystals of 2-[(carboxymethyl)amino]benzoic acid (6). N-Acetylation of 6
afforded 7 as white solid. Subsequent microwave-induced cyclization afforded 1-acetyl-
1
H-indol-3-yl acetate (3) in good yield.
Scheme 2 shows the reaction via a nucleophilic attack by 1-acetyl-1H-indol-3-yl
acetate (3), at position C(2) of isatin (2), resulting in the opening of the indole ring,
followed by an intramolecular exo-trig cyclization to give quindoline-11-carboxylic acid
(
8), which was decarboxylated by heating in diphenylether to yield quindoline (9).
Methylation was carried out with iodomethane in tetrahydrothiophene 1,1-dioxide to
afford orange-brown crystals of 10.
Conversion of the hydriodide 10 to cryptolepine (1) was carried out by the method
of Bierer et al. [15]. Compound 1 crystallized from CHCl /MeOH as purple needles.
3
The physical characteristics of 10 as well as the NOESY correlations of the MeN group

Helvetica Chimica Acta – Vol. 91 (2008)
1977
Scheme 1. Synthesis of 1-Acetyl-1H-indol-3-yl Acetate
Scheme 2. Synthesis of Cryptolepine
at d(H) 5.00 (s) with HꢀC(4) at d(H) 8.73 (d, J ¼ 9) and HꢀC(6) at d(H) 8.75 (d, J ¼
) in the two-dimensional NMR spectra of 10 unambiguously established the identity
8
of the final product as cryptolepine, thereby discarding the possibility of formation of
its structural isomer cryptotackiene (11; Fig. 1), which would obviously show a
different set of NOESY correlations around the MeN group.
2
.2. Absorption and Fluorescence Measurements. In non-polar solvents like p-
dioxane and tetrahydrofuran, the lowest energy structured absorption band of
cryptolepine appeared in the range 330 – 430 nm, while in polar solvents (MeCN,
EtOH, and MeOH) an additional broad absorption band appeared in the wavelength
range 400 – 500 nm. The structured band was due to the excitation of the normal
molecule, while the broad, structureless band was due to the excitation of the charge-

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Helvetica Chimica Acta – Vol. 91 (2008)
Fig. 1. Observed NOEs in 1 and structure of cryptotackiene
transfer (CT) species present in polar media. Fig. 2 shows the representative absorption
spectra of cryptolepine in 1,4-dioxane and EtOH. The figure reflects an appreciable
blue shift for the structured absorption band in polar solvents. This has been ascribed to
the stabilization of the highest occupied molecular orbital (HOMO) in the polar
environment.
Fig. 2. Absorption spectra of cryptolepine in 1,4-dioxane and EtOH
In non-polar solvents the fluorescence spectrum of cryptolepine appeared as a
structured band in the range 400 – 550 nm. The excitation spectrum corresponding to
this emission resembled the absorption spectrum. Further, the excitation and
fluorescence spectra showed mirror image relationship. This confirmed that the
fluorescence originated directly from the lowest excited state (S ) of the molecule. In
1
polar solvents, the fluorescence spectrum of cryptolepine got modified drastically. In
Fig. 3, the fluorescence emission and excitation spectra of the molecule in 1,4-dioxane
and EtOH solvents have been shown. The normal fluorescence band observed in the
non-polar media decreased remarkably and a lower energy, broad and structureless
emission band (450 – 700 nm) characteristic of a charge-transfer spectrum appeared.

Helvetica Chimica Acta – Vol. 91 (2008)
1979
Fig. 3. Fluorescence emission and excitation spectra of 1 in a) 1,4-dioxane and b) EtOH (excitation and
monitoring wavelengths are indicated in the insets)
This low energy emission showed a mirror relationship with the broad absorption
(400 – 500 nm) observed in polar solvents. Irrespective of the wavelength of excitation
the CT emission dominated in polar solvents. This indicated that in the photo-excited
state (S ) the equilibrium shifted more towards the CT species in polar media. The
1
photophysical parameters of cryptolepine in some selected solvents have been
described in the Table.
Table. Photophysical Parameters of Cryptolepine in Selected Solvents
Solvent
Absorption maximum
nm]
Fluorescence maximum Fluorescence quantum yield
[
[nm]
Normal emission CT emission
1
,4-Dioxane 374 (s), 394, 405 (s)
415 (structured)
415 (structured)
538 (broad)
0.020
0.021
–
–
–
THF
MeCN
373 (s), 391, 404 (s)
350 (s), 367, 388 (s),
0.036
4
28 (broad)
354 (s), 370, 386 (s),
33 (broad)
353 (s), 369, 434 (broad) 543 (broad)
EtOH
539 (broad)
–
–
0.031
0.024
4
MeOH
3
. Conclusion. – With the simple expedient of dielectric heating, i.e. using a
domestic microwave oven, we simplified the synthesis of a major drug molecule,
cryptolepine, to such an extent that starting from readily available inexpensive starting
materials viz. anthranilic acid and isatin, the drug could be obtained within a single day.
Use of microwaves and carrying out the key condensation step in aqueous phase
offered additional advantage of environment-friendliness. Our protocol simplifies and
effectively complements the earlier exhaustive procedures in a relatively ꢂgreenerꢀ way.
The absorption and fluorescence spectral studies reveal that there is a solvent
dependent equilibrium between the normal and the charge transfer species of
cryptolepine. In polar solvents, the equilibrium shifted towards the CT species both

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Helvetica Chimica Acta – Vol. 91 (2008)
in the ground and the photo-excited state. These observations will be helpful in future
projects targeted at tuning the efficacy of the skeleton or its simple derivatives as a
drug.
Experimental Part
General. The technical-grade anthranilic acid was crystallized from H O, containing a little HCl,
2
twice, until the material showed reliable m.p. (1448). All other chemicals employed were either of A. R.
grade or purified before use. All the solvents were distilled and dried (wherever necessary) before use.
Column chromatography (CC): silica gel SRL (SiO ; spherical, 60 – 120 mesh). Microwave irradiations:
2
1
200W BPL-SANYO domestic microwave oven, pierced in the roof. Melting points: electrical melting
point apparatus (Sunvic, U. K.). Absorption and fluorescence spectra: Shimadzu MPS 2000 spectro-
photometer and SpexFluorolog II spectrofluorimeter, respectively. For the spectral measurements,
spectroscopic grade solvents from Aldrich Chemicals were employed. The spectral studies were
performed at ambient temperature. The fluorescence quantum yields were determined against quinine
sulfate in 0.1n H SO soln. (f ¼ 0.53) [31]. IR Spectra: Perkin-Elmer FT/IR-300E spectrophotometer; in
2
4
ꢀ
1
1
13
cm . H- and C-NMR spectra: Bruker AV 300 (300 MHz) instrument using (D )DMSO as solvent with
6
1
13
Me Si ( H) and the middle resonances of (D )DMSO (octet, 40.0, for C) as internal standards. d in ppm,
4
6
J in Hz. Two dimensional NMR experiments: Bruker Biospin DRX 500 instrument. MS: JEOL JMS 600
instrument with direct inlet; in m/z. CHN analyses: Perkin-Elmer 2400 Series-II CHNS/O Analyzer.
2
-[(Carboxymethyl)amino]benzoic Acid (6). 4 (2.1 g, 15 mmol) in 2.0 ml H O was dissolved in a
2
soln. of 0.65 g NaOH in 1.8 ml H O, and was mixed cautiously, to avoid excessive foaming, with a soln. of
2
5
(1.4 g, 17 mmol) and 0.81 g Na CO in 2 ml H O. The mixture was refluxed carefully under dielectric
2 3 2
heating conditions for 14 min at 70% power level. The partially solidified mixture was dissolved in warm
n NaOH and then acidified with conc. HCl. The resulting off-white solid that promptly turned to snuff
1
color in acid soln. was collected and crystallized from MeOH/H O to yield 2.5 g (90%) of 6. Off-white
2
crystals turning snuff readily. M.p. 2208 (dec). IR (KBr): 3374 (NH str.), 3260 – 2820 (br., peak at 3164,
1
CO H), 2369, 1725 (CO str.), 1662, 1221. H-NMR: 2.51 (br. s, NH); 3.99 (s, ArNHCH CO H); 7.80 –
2
2
2
13
6
1
.60 (m, 4 arom. H); 12.80 (br. s, CO H). C-NMR: 44.7 (t, C(2)); 111.0 (d, C(3’)); 112.0 (s, C(1’));
15.2 (d, C(5’)); 132.1 (d, C(6’)); 134.9 (d, C(4’)); 150.4 (s, C(2’)); 170.1 (s, C(7’)); 172.2 (s, C(1)). Anal.
2
calc. for C H NO : C 55.38, H 4.62, N 7.18, found: C 55.34, H 4.48, N 7.04.
9
9
4
2
-[Acetyl(carboxymethyl)amino]benzoic Acid (7). To a soln. of 1.70 g anh. Na CO in 1.70 ml H O,
2 3 2
1.95 g (10 mmol) of 6 was added and, after dissolution by 73 ml acetic anhydride, irradiated under
microwave for 4 min. The solid that separated out on acidification with conc. HCl was collected, washed
with a little H O and dried to afford 2.20 g (92%) of 7 crystallized from MeOH containing a few drops of
2
CHCl . Off-white crystals. M.p. 208 – 2108 (dec.). IR (KBr): 3434 (NH str.), 3220 – 2860 (br., peak at
3
1
3
019, CO H), 2365, 1725 (CO str.), 1601, 1391, 1229. H-NMR: 1.69 (s, MeCO); 3.63 (d, J ¼ 17.2,
2
ArN(Ac)CHHCO H); 4.61 (d, J ¼ 17.2, ArN(Ac)CHHCO H); 7.93 – 7.50 (m, 4 arom. H); 12.84 (br. s,
2
2
13
CO H). C-NMR: 22.2 (q, C(9’)); 51.3 (t, C(2)); 129.1 (d, C(3’)); 129.9 (s, C(1’)); 131.0 (d, C(5’)); 131.7
2
(d, C(6’)); 133.7 (d, C(4’)); 142.9 (d, C(2’)); 167.1 (s, C(8’)); 169.5 (s, C(7’)); 171.0 (s, C(1)). Anal. calc. for
C H NO : C 55.70, H 4.64, N 5.91; found: C 55.96, H 4.59, N 6.20.
11
11
5
1
-Acetyl-1H-indol-3-yl Acetate (3). In a mixture of 9 ml Ac O and 1.7 ml Et N, 1.65 g (7 mmol) of
2
3
powdered 7 was dissolved, and irradiated under microwave at 80% power level for 4 min under strict N2
atmosphere. Most of the liquid was then evaporated in vacuo. The remaining oily residue on shaking with
6
0 ml H O yielded a crude solid, which on purification through CC afforded 1.30 g (86%) of 3. Snow
2
1
white crystals. M.p. 85 – 868 (dec.). IR (KBr): 1745 (CO str.), 1699, 1451, 1380, 1211. H-NMR: 2.39 (s,
OCOMe); 2.62 (s, NCOMe); 7.31 (t, J ¼ 7.5, HꢀC(5)); 7.37 (t, J ¼ 7.5, HꢀC(6)); 7.51 (d, J ¼ 7.6,
13
HꢀC(7)); 7.89 (s, HꢀC(2)); 8.36 (d, J ¼ 7.6, HꢀC(4)). C-NMR: 21.0 (q, C(13)); 24.2 (q, C(11)); 116.2
(d, C(7)); 116.5 (d, C(6)); 118.3 (d, C(4)); 124.0 (d, C(5)); 124.1 (s, C(3)); 126.2 (d, C(2)); 133.1 (s, C(8));
1
34.1 (s, C(9)); 168.8 (s, C(10)); 169.9 (s, C(12)). Anal. calc. for C H NO : C 66.36, H 5.07, N 6.45;
12 11 3
found: C 66.52, H 5.07, N 6.88.

Helvetica Chimica Acta – Vol. 91 (2008)
1981
10H-Indolo[3,2-b]quinoline-11-carboxylic Acid (8). Powdered 3 (3.62 g, 15 mmol) was added to a
well cooled, N -purged soln. of isatin (2; 1H-indole-2,3-dione; 2.17 g, 15 mmol) in 100 ml 6n KOH. The
2
mixture was refluxed carefully under dielectric heating conditions for 16 min keeping the power level at
7
0%. H O (60 ml) was then added. The mixture was heated to 708, while drawing air through the soln. for
2
2
0 min. The soln. was filtered hot through a Celite pad, the bed rinsed with hot H O, an equal volume of
2
EtOH was added and then the soln. was brought to pH 2 with 6n HCl and chilled. The resulting very fine
yellow precipitate was collected, washed with H O, followed by a little EtOH and dried under vacuum to
2
afford 2.7 g (70%) of 8. Very fine yellow crystals. M.p. 3228. IR (KBr): 3345 (NH str.), 3040 – 2780
1
(
broad, peak at 2927, CO H), 2369, 1742 (CO str.), 1675, 1574, 1437, 1251. H-NMR: 7.34 (t, J ¼ 7.6,
2
HꢀC(7)); 7.70 (t, J ¼ 8, HꢀC(2)); 7.70 (d, J ¼ 8, HꢀC(6)); 7.66 (t, J ¼ 8, HꢀC(8)); 7.76 (t, J ¼ 8,
13
HꢀC(3)); 8.29 (m, HꢀC(9)); 8.37 (d, J ¼ 8, HꢀC(4)); 9.08 (m, HꢀC(1)); 11.5 (br. s, NH). C-NMR:
11.8 (s, C(14)); 113.0 (d, C(9)); 120.9 (s, C(15)); 120.9 (d, C(8)); 121.8 (d, C(6)); 124.1 (s, C(17)); 125.4
d, C(7)); 126.5 (d, C(1)); 127.3 (d, C(2)); 129.8 (d, C(3)); 131.0 (d, C(4)); 132.7 (s, C(11)); 142.4 (s,
C(13)); 143.6 (s, C(18)); 145.0 (s, C(16)); 168.2 (s, C(12)). Anal. calc. for C H N O : C 73.28, H 3.82, N
1
(
16
10
2
2
1
0.69; found: C 73.39, H 3.45, N 10.91.
0H-Indolo[3,2-b]quinoline (9). 2.6 g (10 mmol) of 8 in 20 ml diphenyl ether heated in an oil bath
1
for 4 h at 2508. The mixture was cooled, then 30 ml petroleum ether (PE) was added and filtered. The
residue was washed with PE, dried, and on crystallization from MeOH 1.64 g (76%) of 9 were obtained.
Light yellow crystals. M.p. 248 – 2508. IR (KBr): 3414 (NH str.), 1610, 1564, 1484, 1460, 1394, 1332, 1219.
1
H-NMR: 7.28 (t, J ¼ 7, H ꢀC(7)); 7.56 (t, J ¼ 7, H ꢀC(8)); 7.58 (d, J ¼ 7, H ꢀC(9)); 7.64 (t, J ¼ 8, HꢀC(2));
7
.66 (t, J ¼ 8, HꢀC(3)); 8.11 (d, J ¼ 7, H ꢀC(6)); 8.20 (d, J ¼ 8, HꢀC(1)); 8.29 (s, HꢀC(11)); 8.37 (d, J ¼ 8,
13
HꢀC(4)); 11.4 (br. s, NH). C-NMR: 112.0 (d, C(9)); 113.5 (d, C(8)); 119.8 (d, C(6)); 121.5 (s, C(16));
1
21.8 (d, C(7)); 125.3 (d, C(2)); 126.5 (d, C(1)); 127.2 (s, C(14)); 128.0 (d, C(4)); 129.2 (d, C(3)); 130.2 (d,
þ
C(11)); 133.0 (s, C(13)); 143.9 (s, C(17)); 144.5 (s, C(12)); 146.2 (s, C(15)). EI-MS: 218 (100, M ), 190
(
4
þ
[M ꢀ C H ] ), 164, 115, 109, 89. Anal. calc. for C H N : C 82.57, H 4.59, N 12.84; found: C 82.82, H
2
4
15 10
2
.45, N 13.10.
Synthesis of 5-Methyl-10H-indolo[3,2-b]quinolin-5-ium Iodide (10). A suspension of 9 (2.2 g,
1
0 mmol) and MeI (7 ml, 80 mmol) was heated for 4 min under dielectric conditions (with
tetrahydrothiophene 1,1-dioxide) at 70% power level in a carefully sealed round bottom flask. The
excess MeI was removed in vacuo and the brown precipitate was collected, washed with Et O, and dried,
2
yielding 3.3 g (88%) of 10. Crystallization from H O containing a few drops of MeOH gave bright yellow
2
1
crystals. M.p. 2808. IR (KBr): 3436 (NH str.), 2369, 1607, 1498, 1462, 1347, 1250. H-NMR: 5.00 (s, MeN);
7
.48 (t, J ¼ 8, HꢀC(7)); 7.79 (d, J ¼ 8, HꢀC(9)); 7.89 (t, J ¼ 8, HꢀC(8)); 7.91 (t, J ¼ 9, HꢀC(3)); 8.13 (t,
J ¼ 9, HꢀC(2)); 8.55 (d, J ¼ 8, HꢀC(1)); 8.73 (d, J ¼ 9, HꢀC(4)); 8.75 (d, J ¼ 8, HꢀC(6)); 9.25 (s,
13
HꢀC(11)); 12.81 (br. s, NH). C-NMR: 41.1 (q, C(18)); 114.0 (d, C(9)); 114.6 (s, C(15)); 118.7 (d, C(8));
1
22.2 (d, C(7)); 125.6 (d, C(6)); 127.0 (s, C(14)); 127.1 (d, C(3)); 127.9 (d, C(1)); 130.7 (d, C(4)); 133.3 (d,
C(2)); 134.1 (s, C(16)); 134.8 (d, C(11)); 136.2 (s, C(13)); 138.9 (s, C(17)); 146.5 (s, C(12)). Anal. calc. for
C H N : C 82.57, H 4.59, N 12.84; found: C 82.82, H 4.45, N 13.10.
15
10
2
Synthesis of Cryptolepine (¼ 5-Methyl-5H-indolo[3,2-b]quinoline; 1). Hydroiodide 10 (1.8 g,
5
mmol) was shaken with a 5% soln. of Na CO (100 ml) and then extracted with CHCl (2 ꢁ 200 ml).
2
3
3
Na CO was added to the soln., the mixture was concentrated and the adsorbed product was loaded onto
2
3
a short column of basic alumina. Elution with CHCl to elute the quindoline impurity followed by further
3
elution with 2% MeOH in CHCl gave 0.70 g (61%) of 1 as a purple solid. M.p. 172 – 1748. IR (KBr):
3
1
2
373, 1628, 1493, 1457, 1357, 1302, 1252, 1128. H-NMR: 4.33 (s, MeN); 6.77 (t, J ¼ 8, HꢀC(7)); 7.30 (t,
J ¼ 8, HꢀC(2)); 7.40 (d, J ¼ 8, HꢀC(9)); 7.46 (t, J ¼ 8, HꢀC(8)); 7.70 (t, J ¼ 9, HꢀC(3)); 7.84 (d, J ¼ 9,
13
HꢀC(4)); 7.94 (d, J ¼ 8, HꢀC(6)); 8.00 (d, J ¼ 9, HꢀC(1)); 8.28 (br. s, HꢀC(11)). C-NMR: 37.4 (q,
C(18)); 113.2 (s, C(16)); 115.3 (d, C(4)); 117.2 (d, C(9)); 117.4 (d, C(2)); 123.8 (d, C(11)); 123.84 (d,
C(3)); 124.6 (s, C(13)); 125.0 (d, C(1)); 129.0 (d, C(7)); 129.02 (d, C(6)); 130.6 (d, C(8)); 132.9 (s, C(14));
þ
þ
1
38.3 (s, C(12)); 142.8 (s, C(15)); 158.3 (s, C(17)). EI-MS: 232 (100, M ), 217 ([M ꢀ Me] ), 204 ([M ꢀ
þ
C H ] ), 190, 146, 116, 109, 88.
2
4

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Helvetica Chimica Acta – Vol. 91 (2008)
We thank Mr. P. Ghosh, Mr. S. Chatterjee, Mr. J. Ghosh, and Mr. S. Bhowmik of the organic
instrumentation laboratory, Centre of Advanced Studies on Natural Products including Organic
Synthesis, Department of Chemistry, Calcutta University for recording the spectral data.
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Received April 10, 2008