A short and convenient synthesis and evaluation of the antiinfective properties of indoloquinoline alkaloids: 10H-indolo[3,2-b]quinoline and 7H-indolo[2,3-c]quinolines

Article abstract of DOI:10.1002/jhet.5570450232

(Chemical Equation Presented) 10H-Indolo[3,2-b]quinoline and 7H-indolo[2,3-c]quinoline have been synthesized in two steps using a modified approach to our previous reported method. Starting from commercially available 3-amino-quinoline and phenylboronic a

Full text of DOI:10.1002/jhet.5570450232

Mar-Apr 2008
507
A Short and Convenient Synthesis and Evaluation of the
Antiinfective Properties of Indoloquinoline Alkaloids: 10H-
Indolo[3,2-b]quinoline and 7H-Indolo[2,3-c]quinolines
Jagan R. Etukala, E. V. K. Suresh Kumar, Seth Y. Ablordeppey*
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University,
Tallahassee, Florida 32307. seth.ablordeppey@famu.edu
Received July 14, 2007
H
N
R
R
N
N
CH3
N
CH3
I
H
I
(c)
(c)
R
B(OH)2
H
N
H
NH2
N
(a)
(b)
R
+
R
R
+
N
N
N
H
N
N
(d)
(d)
N
R1
N
R
R
I
N
N
I
CH3
CH3
R1
(a) Cu(OAc)2, DCM, (C2H5)3N, Molecular sieve powder, RT, 12-24 hr.
(b) Pd(OAc)2, CF3COOH, 60 oC; (c) CH3I, Tetramethylene sulfone (TMS), 110 oC;
(d) (i) DME, NaH, C6H11(CH2)5I, (ii) CH3I, TMS, 110 oC.
10H-Indolo[3,2-b]quinoline and 7H-indolo[2,3-c]quinoline have been synthesized in two steps using a
modified approach to our previous reported method. Starting from commercially available 3-aminoquinoline
and phenylboronic acid, the first step involved a copper acetate-catalyzed coupling reaction and the second
utilized a palladium acetate-catalyzed intramolecular arylation reaction in the presence of trifluoroacetic acid
as solvent. The anti-infective activity of a selected number of the compounds was also evaluated.
J. Heterocyclic Chem., 45, 507 (2008).
antibacterial, antifungal, antimalarial, anticancer, antiplatelet
aggregation, analgesic, antihypertensive and several others
[9]. The mechanism by which one structure could elicit such
an array of activities has not been completely elucidated.
However, several lines of evidence in the literature suggest
that DNA intercalation and topoisomerase II inhibition are
prime suspects [10]. Indeed, cryptolepine is reported to bind
tightly to DNA and is cytotoxic toward B16 melanoma cells
[11].
As a result of the interesting biological activities
associated with the indoloquinoline alkaloids, several
synthetic procedures have been reported in the literature.
Mohan and colleagues [12,13] reported a photochemical
synthetic procedure and a Fischer indole synthesis [14]
INTRODUCTION
Several research publications in the last 30 years have
demonstrated that cryptolepine and other indoloquinoline
alkaloids isolated from Cryptolepis sanguinolenta, display
interesting biological activities [1-4]. Cryptolepine (1),
neocryptolepine (2) and isocryptolepine (3) are three of the
thirteen alkaloids identified in extracts from the root of C.
sanguinolenta (Fig 1) [5-8]. Isoneocryptolepine (4), also
referred tp as 4-methyl-5,6-benz-4-ꢀ-carboline, was first
synthesized by Kermack, et al. [Kermack, W. O.; Slater, R.
H. J. Chem Soc., 1928, 789.] before its subsequent syntheses
by others [5-8]. The biological activities associated with
cryptolepine and a number of these alkaloids include,
CH3
N
N
D
A
C
D
B
N
A
C
B
N
N
N
N
CH3
N
CH3
CH3
1
4
2
3
Figure 1

508
J. R. Etukala, E. V. K. Suresh Kumar, S. Y. Ablordeppey
Vol 45
towards several angular quindolines. The former approach
is based on a stepwise reaction of a haloquinoline with
aniline and photochemical irradiation of the resultant
intermediate in the presence of an iodine catalyst to afford
isomeric indoloquinolines. Another synthetic method-
ology utilizing selective Buchwald–Hartwig amination
acid was carried out to give 10H-indolo[3,2-b]quinoline
(8c) and 7H-indolo[2,3-c]quinoline (9c) in moderate to
excellent yields (Scheme 2). Ortho substituted
chlorophenyl-3-aminoquinoline gave selectively only one
product (Table 1). For example, 2-chlorophenyl-3-amino-
quinoline led to only 9-chloro-10H-indolo[3,2-b]quinoline
(8a in Table 1) without loss of the halogen atom in 85%
yield. On the other hand, meta and para-substituted
phenyl 3-aminoquinolines led to a mixture of 10H-
indolo[3,2-b]quinolines and 7H-indolo[2,3-c]quinolines
(Table 1). Thus, this approach now places at our disposal
a strategy of obtaining both compounds in high yields.
For the linear indoloquinolines, we simply substitute at
the ortho-position with a group that can easily be removed
subsequently while the angular 7H-indolo[2,3-c]quino-
lines can be synthesized directly albeit with some linear
indoloquinoline impurity which is easily removed by flash
chromatography. Alkylation of the indoloquinolines was
accomplished as previously reported [20, 22].
Based on previous work in our laboratories, [22] 2 pairs
of alkylated quindolines were evaluated for their
antiinfective properties against AIDS related opportunistic
pathogens. Results recorded in Table 2 show that N-
methylated compound (11) shows no activity at 20 μg/ml,
compound 10, the salt form of compound 1 and compound
12, have weak antifungal properties while compound 13
with ꢀ-cyclohexylpentyl moiety on the indole N atom
appears to have good antiinfective properties. Indeed,
compound 13 is not only very potent and compares
favorably with Amphotericin B, but has lower cytotoxicity
towards Vero cells than Amphotericin B and thus warrant
further Structure-Activity Relationship studies.
with
a
regioselective Pd-catalyzed intramolecular
arylation reaction has also been reported [15]. Zhang [16]
also reported the synthesis of the N-demethylated
precursor isoneocryptolepine via an intramolecular
palladium-catalyzed Buchwald-Hartwig amination [17,
18] and Dutta [19] developed a method for the synthesis
of quindolines using thermal cyclization of 3-arylamino-
3-(2-nitrophenyl)propanal Schiff base. The cyclization
was followed by triethyl phosphite mediated deoxy-
genation to produce the desired product.
A cursory look at the methods stipulated above shows
that several of the reported synthetic methods of
indoloquinoline alkaloids suffer from poor yields, absence
of readily available starting materials, or use reaction
conditions that make it difficult to prepare substituted
indoloquinoline alkaloids. Several years ago [20], we
reported a method intended to alleviate the long delay in
the synthetic approach of Holt and Petrow [21]. However,
the palladium-catalyzed cyclization step resulted in very
low yields. The low yields were attributed to the synthesis
of non-linear indoloquinolines which were not of interest
at the time. In continuation of our research program
involving the design of cryptolepine analogs as novel
anti-infective agents, we have explored a modification of
the previous synthetic approach for the preparation of
quindolines. In this paper, we report a short and
convenient synthesis of substituted indoloquinolines using
readily available starting materials and reagents which
provides some advantages over several of the previous
approaches. The biological evaluation of two sets of linear
versus angular quindolines for their anti-infective
activities is also reported.
Scheme 1
R
B(OH)2
H
N
NH2
(a)
R
+
80-90%
N
N
RESULTS AND DISCUSSION
5
6
7
R= Cl, CF3, OCF3, OCH3, COOCH(CH3)2
It was of interest to investigate A-ring substituted
indoloquinolines as new anti-infective agents. The
commercial availability of several substituted phenyl
boronic acids makes the regio-selective Pd(OAc)2-
catalyzed intramolecular arylation approach a preferred
tool to easily access these A-ring functionalized 10H-
indolo[3,2-b]quinolines and 7H-indolo[2,3-c]quinolines.
As a first step towards the synthesis of these scaffolds, we
investigated the reaction of 3-aminoquinoline with
substituted phenyl boronic acids in the presence of copper
acetate and triethylamine. This reaction gave N-
phenylquinoline-3-amines in good yields (80-90%).
Next, a palladium acetate-catalyzed intramolecular C-C
bond formation reaction in the presence of trifluoroacetic
Reagents: (a) Cu(OAc)2, DCM, (C2H5)3N, Molecular sieve powder, RT,
12-24 hr.
In conclusion, the palladium catalyzed carbon-carbon
bond formation is presented in this paper as a convenient
method for the preparation of substituted 10H-indolo[3,2-
b]quinoline and 7H-indolo[2,3-c]quinolines in high
yields. However, this method has limitations as well.
Ortho substituted phenyl boronic acids cannot produce
angular indoloquinolines and thus other methods must be
used to obtain such. Advantages such as product
selectivity in case of ortho substitution, use of
inexpensive catalyst, simple work up protocols and short

Mar-Apr 2008
A Short and Convenient Synthesis and Evaluation of the Antiinfective Properties
509
Scheme 2
H
R
N
R
N
N
N
H3C
I
10; R = H
(b)
11; R= H
I
CH3
H
(b)
R
H
H
N
N
(a)
R
R
+
N
N
N
N
H
9
8
7
(c)
(c)
R1
N
R
R1 =
CH2(CH2)3CH2C6H11
R
N
N
N
H3C
12; R = H
13; R = H
CH3
I
R1
I
Reagents: a) Pd(OAc)2, CF3COOH, 60 °C; b) CH3I, Tetramethylene sulfone, 110 °C; c) (i) DME,
NaH, C6H11(CH2)5I, (ii) CH3I, Tetramethylene sulfone, 110 °C.
Table 1
Physicochemical data of 10H-indolo[3,2-b]quinoline and 7H-indolo[2,3-c]quinolines.
1
11
R
1
9
H
N
4
R
8
N
N
N
H
4
6
7
A
B
Entry
Product (A) (8)
M.P for (8) °C
Product (B) (9)
M.P for (9) °C
Product selectivity
Yields
(%)
ratio (A:B)a
a
b
c
d
e
f
g
h
i
9-Cl
9-OCH3
Hb
7-Cl
8-Cl
272-274
180-181
249-251
250-252
>270c
252-254
218-219
228-230
276-278
220-221
No product
No product
H
10-Cl
9-Cl
10-CF3
10-OCF3
10-OMe
9-OMe
10-CO2iPr
-
-
100:0
100:0
10:90
20:80
6:94
10:90
12:88
10:90
6:94
85
74
80
75
71
78
80
77
71
70
242-244
146-148
295-296
295-296
233-235
142-144
192-194
166-168
7-CF3
7-OCF3
7-OCH3
8-OCH3
7-CO2iPr
j
15:85
a the product ratio is based on isolated yields.b Previously reported in reference 20. c Decomposed.
Table 2
Antifungal Activity of Indoloquinolines
Compound
Anti-infective Activityb: IC 50/MIC/MFC (μg/mL)c
Cytotoxicity,
C. albicans
C. neoformans
A. fumigatus
IC50 (μg/mL) in Vero
Cells
3.2
NT
NT
10a
2.0/>20/>20
>20/>20/>20
>20/>20/>20
15.6/>20/>20
>20/>20/>20
15.0/>20/>20
>20/>20/>20
NT
NT/2.5/>20
11
12
13
0.8/2.5/10.0
0.3/0.6/1.3
1.5/2.5/5.0
1.5/2.5/2.5
3.5/5.0/10.0
1.5/2.5/2.5
>10
6.5
Amph. B
a = Previously reported in references 22 and 23. NT: Not Tested. b = For the methods of determination of biological activities, refer to
reference 22. IC50 = Concentration that inhibits 50% of fungal growth or produces cytotoxicity in 50% of Vero cells; MIC = Minimum
inhibitory concentration; MFC = Minimum fungicidal concentration.

510
J. R. Etukala, E. V. K. Suresh Kumar, S. Y. Ablordeppey
Vol 45
J = 1.8, 6.9 Hz), 8.06 (d, 1H, J = 8.1 Hz), 8.21 (d, 1H, J = 8.4
Hz), 8.32 (s, 1H), 8.80 (s, 1H).
reaction times, make this method a useful and attractive
procedure for the synthesis of indoloquinoline alkaloids.
Evaluation of alkylated indoloquinolines 10-13
7-Trifluoromethoxy-10H-indolo[3,2-b]quinoline (8g). 1H
nmr (CDCl3): ꢀ 7.44 (d, 2H, J = 1.8 Hz), 7.60-7.54 (m, 1H),
7.70-7.66 (m, 1H), 7.94 (d, 1H, J = 8.1 Hz), 8.06 (s, 1H), 8.18
(brs, 1H), 8.32 (d, 1H, J = 8.4 Hz), 8.40 (d, 1H, J = 0.9 Hz).
7-Methoxy-10H-indolo[3,2-b]quinoline (8h). 1H nmr
(CDCl3): ꢀ 3.90 (s, 3H), 7.25 (s, 2H), 7.62 (t, 1H, J = 6.9 Hz),
7.74 (t, 1H, J = 6.9 Hz), 7.86 (d, 1H, J = 8.1 Hz), 8.06 (d, 1H, J
= 8.4 Hz), 8.20 (brs, 1H), 8.76 (d, 1H, J = 2.1 Hz), 8.84 (d, 1H, J
= 2.4 Hz).
indicates that 7H-indolo[2,3-c]quinolines display
a
favorable antifungal profile and thus, can serve as a new
lead scaffold for further evaluation and development.
EXPERIMENTAL
General Procedure for the synthesis of phenyl-3-amino-
quinoline (7a-i). A mixture of 3-aminoquinoline (1 g, 6.94
mmol), 4-chlorophenylboronic acid (1.63 g, 10.41 mmol, 1.5
eq), Et3N (1.45 mL, 10.41 mmol, 1.6 eq), Cu(OAc)2 (1.90 g,
10.41 mmol, 1.6 eq), molecular sieves, 4 Å (2 g) in CH2Cl2 (30
mL) was allowed to stir at room temperature and monitored by
TLC for 12-24 hours. The reaction mixture was quenched by
drop-wise addition of aqueous NH3 (15 mL). The resulting
mixture was extracted with CH2Cl2 (3 x 50 mL), washed with
H2O, brine solution and dried over anhydrous Na2SO4. The
solvent was evaporated under reduced pressure and the pure
product was obtained by column chromatography using EtOAc
8-Methoxy-10H-indolo[3,2-b]quinoline (8i). 1H nmr
(DMSO-d6): ꢀ 3.90 (s, 3H), 6.86 (dd, 1H, J = 2.1 , 6.6 Hz), 7.01
(d, 1H, J = 1.8 Hz), 7.50 (t, 1H, J = 7.2 Hz), 7.60 (t, 1H, J = 7.2
Hz), 8.04 (d, 1H, J = 2.8 Hz), 8.11 (d, 1H, J = 8.4 Hz), 8.15 (s,
1H), 8.18 (d, 1H, J = 8.7 Hz,) 11.24 (s, 1H).
10H-Indolo[3,2-b]quinoline-7-carboxylic acid isopropyl
1
ester (8j). H nmr (CDCl3): ꢀ 1.41 (s, 3H), 1.43 (s, 3H), 5.40-
5.30 (m, 1H), 7.48 (dd, 1H, J = 0.6, 8.1 Hz), 7.60-7.56 (m, 1H),
7.72-7.68 (m, 1H), 7.96 (dd, 1H, J = 1.5, 6.6 Hz), 8.08 (s, 1H),
8.24 (brs, 1H), 8.38-8.32 (m, 2H), 9.26 (d, 1H, J = 1.8 Hz).
1
7H-indolo[2,3-c]quinoline (9c). H nmr (DMSO-d6): ꢀ 12.20
1
(s, 1H), 9.26 (s, 1H), 8.80 (dd., 1H, J = 0.9, 7.2 Hz), 8.66 (d, 1H,
J = 8.4 Hz), 8.17 (d, 1H, J = 7.8 Hz), 7.76-7.72 (m, 2H), 7.66-
7.54 (m, 2H), 7.40 (t, 1H, J = 8.4 Hz).
and hexanes as eluent. H NMR (DMSO-d6): ꢀ 7.24 (d, 2H, J =
8.7 Hz) , 7.34 (d, 2H, J = 9.0 Hz), 7.46-7.52 (m, 2H) , 7.78-7.82
(m, 1H), 7.84-7.90 (m, 2H), 8.68 (d, 1H, J = 3.0 Hz), 9.40 (s,
1H). Other substituted phenyl 3-aminoquinolines were similarly
obtained.
1
10-Chloro-7H-indolo[2,3-c]quinoline (9d). H nmr (DMSO-
d6): ꢀ 7.58-7.56 (dd, 1H, J = 2.1, 6.6 Hz), 7.74-7.62 (m, 3H),
8.16 (d, 1H, J = 8.1 Hz), 8.72 (d, 1H, J = 1.5 Hz), 8.80 (d, 1H, J
= 8.1 Hz), 9.26 (s, 1H), 12.34 (s, 1H).
General procedure for the synthesis of 10H-indolo[3,2-
b]quinoline and 7H-indolo-[3,2-c]quinoline analogs (8 and 9).
A mixture of 4-chlorophenylquinolin-3-yl-amine (200 mg, 0.78
mmol), CF3COOH (8 mL) and Pd(OAc)2 (176 mg, 0.78 mmol)
was allowed to reflux at 60°C for 4-6 hour. The reaction mixture
was allowed to cool to room temperature, poured on ice cold
water (15 ml), neutralized with aqueous NH3 and extracted with
EtOAc (3 x 50 mL), washed with brine and dried over
anhydrous Na2SO4. The solvent was removed under reduced
pressure and the crude product was purified on chromatographic
column using EtOAc and hexanes as eluent. The pure products
were obtained as solids [(8d, 30 mg, 15%), (9d, 120 mg, 60%)].
1
9-Chloro-7H-indolo[2,3-c]quinoline (9e). H nmr (CD3OD):
ꢀ 7.38 (dd, 1H, J = 1.5, 6.9 Hz), 7.68 (t, 2H, J = 6.9 Hz), 7.77 (t,
1H, J = 7.2 Hz), 8.16 (d, 1H, J = 8.4 Hz), 8.56 (d, 1H, J = 8.4
Hz), 8.72 (d, 1H, J = 8.1 Hz), 9.13 (s, 1H).
1
10-Trifluoromethyl-7H-indolo[2,3-c]quinoline (9f). H nmr
(CD3OD): ꢀ 7.70 (t, 1H, J = 8.1 Hz), 7.84-7.78 (m, 3H), 8.18 (d,
1H, J = 8.4 Hz), 8.72 (d, 1H, J = 2.4 Hz), 8.83 (s, 1H), 9.18 (s,
1H).
10-Trifluoromethoxy-7H-indolo[2,3-c]quinoline (9g). 1H
nmr (DMSO-d6): ꢀ 7.56 (dd, 1H, J = 1.2, 7.8 Hz), 7.70-7.64 (m,
1H), 7.84 (d, 1H, J = 8.7 Hz), 8.16 (d, 1H, J = 7.2 Hz), 8.68 (s,
1H), 8.78-7.73 (m, 1H), 8.80 (d, 1H, J = 8.1 Hz), 9.31 (s, 1H),
12.40 (s, 1H).
1
9-Chloro-10H-indolo[3,2-b]quinoline (8a). H nmr (CDCl3):
ꢀ 7.40 (t, 1H, J = 7.8 Hz), 7.62 (d, 1H, J = 6.9 Hz), 7.80-7.68 (m,
2H, 8.32 (dd, 1H J = 1.2, 7.5 Hz), 8.48 (d, 1H, J = 8.1 Hz), 8.68
(dd, 1H, J = 1.2, 6.66 Hz), 8.92 (brs, 1H) 9.32 (s, 1H).
9-Methoxy-10H-indolo[3,2-b]quinoline (8b). 1H nmr
(DMSO-d6): ꢀ 4.00 (s, 3H), 7.14 (d, 1H, J = 7.5 Hz), 7.30 (t, 1H,
J = 8.1 Hz), 7.66-7.60 (m, 1H), 7.76 (m, 1H), 8.14 (dd, 1H, J =
1.2, 7.2 Hz), 8.18 (d, 1H, J = 8.1 Hz), 8.72 (dd, 1H, J = 0.9, 8.0
Hz), 12.30 (s, 1H), 9.22 (s, 1H).
10-Methoxy-7H-indolo[2,3-c]quinoline (9h). 1H nmr
(DMSO-d6): ꢀ 4.00 (s, 3H), 7.22 (dd, 1H, J = 2.4, 6.3 Hz), 7.68-
7.60 (m, 2H), 7.74 (t, 1H, J = 6.9 Hz), 8.04 (d, 1H, J = 2.1 Hz),
8.14 (d, 1H, J = 7.8 Hz), 8.76 (d, 1H, J = 8.1 Hz), 9.22 (s, 1H),
12.00 (s, 1H).
1
9-Methoxy-7H-indolo[2,3-c]quinoline (9i). H nmr (DMSO-
10H-Indolo[3,2-b]quinoline (8c). 1H nmr (DMSO-d6): ꢀ 7.30
(dd, 1H, J= 6.5, 7.1 Hz) , 7.64-7.58 (m, 4H), 7.98 (d, 1H,
J=8.2Hz), 8.20 (d, 1H, J = 8.4Hz), 8.30 (s, 1H), 8.42 (d, 1H,
J=8.4Hz), 11.40 (s, 1H, NH).
d6): ꢀ 4.10 (s, 3H), 6.86 (d, 1H, J = 7.8 Hz), 7.30 (d, 1H, J = 7.5
Hz), 7.50 (t, 1H, J = 8.1 Hz), 7.64-7.58 (m, 2H), 8.10 (dd, 1H, J
= 1.2, 6.3 Hz), 9.20 (s, 1H), 9.52 (dd, 1H, J = 1.8, 6.6 Hz), 12.20
(s, 1H).
1
7-Chloro-10H-indolo[3,2-b]quinoline (8d). H nmr (DMSO-
7H-Indolo[2,3-c]quinoline-10-carboxylic acid isopropyl
1
d6): ꢀ 7.76-7.60 (m, 4H), 8.24-8.16 (m, 2H), 8.36 (d, 1H, J = 1.5
Hz), 8.54 (s, 1H), 11.80 (s, 1H).
ester (9j). H nmr (DMSO-d6): ꢀ 1.39 (s, 3H), 1.41 (s, 3H),
5.26-5.20 (m, 1H), 7.70 (t, 1H, J = 6.9 Hz), 7.82 (t, 2H, J = 6.9
Hz), 8.16 (dd, 1H, J = 1.5, 7.5 Hz), 8.20 (d, 1H, J = 8.4 Hz), 8.70
(d, 1H, J = 8.1 Hz), 9.16 (s, 1H), 9.30 (s, 1H), 12.50 (s, 1H).
5-Methyl-10H-indolo[3,2-b]quinolinium iodide (10). Mp
280–283 °C; 1H nmr (DMSO-d6) ꢀ 5.04 (s, 3 H), 7.52 (ddd, 1H,
J = 7.7, 7.7, 1.0 Hz), 7.86 (d, 1H, J = 8.3 Hz), 7.93 (dd, 1H, J =
7.2, 7.2 Hz), 7.96 (dd, 1H, J = 8.1, 8.1 Hz), 8.17 (ddd, 1H, J =
8.0, 8.0, 1.4 Hz), 8.58 (dd, 1H, J = 7.4, 1.0 Hz), 8.77 (d, 1H, J =
8-Chloro-10H-indolo[3,2-b]quinoline (8e). 1H nmr
(CD3OD): ꢀ 7.44 (dd, 1H, J = 1.5, 6.9 Hz), 7.72 (d, 1H, J = 1.2
Hz), 7.80 (t, 1H, J = 8.1 Hz), 7.96 (t, 1H, J = 7.2 Hz), 8.26 (d,
1H, J = 8.4 Hz), 8.30 (d, 1H, J = 8.4 Hz), 8.44 (d, 1H, J = 8.7
Hz), 8.86 (s, 1H).
1
7-Trifluoromethyl-10H-indolo[3,2-b]quinoline (8f). H nmr
(CD3OD): ꢀ 7.62-7.56 (m, 1H), 7.74-7.66 (m, 2H), 7.86 (dd, 1H,

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A Short and Convenient Synthesis and Evaluation of the Antiinfective Properties
511
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K. Tetrahedron. 2006, 62, 4676.
9.1 Hz), 8.81 (d, 1H, J = 8.5 Hz), 9.30 (s, 1H), 12.87 (s, 1H);
Anal. Calcd. for C16H13N2I, C, 53.35; H, 3.64; N, 7.78. Found: C,
53.33;, H, 3.66; N, 7.69.
5-Methyl-7H-indolo[2,3-c]quinolinium iodide (11). Mp
1
281-283°C; H nmr (DMSO-d6) ꢀ 4.80 (s, 3H), 7.56 (t, 1H, J =
6.9 Hz), 7.85 (t, 1H, J = 6.3 Hz), 7.94 (d, 1H, J = 8.1 Hz), 8.12-
8.09 (m, 2H), 8.56 (d, 1H, J = 9.9 Hz), 8.94 (d, 1H, J = 8.4 Hz),
9.20 (d, 1H, J = 9.6 Hz), 9.92 (s, 1H), 13.20 (s, 1H). Anal. Calcd.
for C16H13IN2: C, 53.35; H, 3.64; N, 7.78, Found: C, 53.18; H,
3.84; N, 7.71.
[4] Egan, T. J. Drug Des. Rev. Online. 2004, 1, 93.
[5] Cimanga, K.; De Bruyne, T.; Pieters, L.; Claeys, M.;
Vlietinck, A. Tetrahedron Lett. 1996, 37, 1703.
[6] Sharaf, H. M.; Schiff, P. L.; Tackie, A. N.; Phoebe, C. H.;
Martin, G. E. J. Heterocycl. Chem. 1996, 33, 239.
10-(5-Cyclohexyl-pentyl)-5-methyl-10H-indolo[3,2-b]quino-
linium iodide (12). M.p 215–217 °C; 1H nmr (DMSO-d6) ꢀ 1.38
(m, 2H), 1.59 (m, 2H), 1.87 (m, 2H), 2.49 (t, 2H, J = 3.0 Hz),
4.70 (t, 2H, J = 7.1 Hz), 5.05 (s, 6H), 7.12 (m, 5H), 7.57 (t, 1H,
J = 8.0 Hz), 8.02 (m, 3H), 8.19 (t, 1H, J = 7.5 Hz), 8.52 (d, 1H,
J = 7.6 Hz), 8.75 (d, 1H, J = 9.0 Hz), 8.85 (d, 1H, J = 8.4 Hz),
9.60 (s, 1H). Anal. Calcd for C27H27IN2: C, 64.04; H, 5.37; N,
5.53. Found: C, 63.77; H, 5.40; N, 5.56.
[7] Pousset, P. L.; Martin, M. T.; Jossang, A.; Bodo, B.
Phytochemistry. 1995, 39, 735.
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Mátyus, P.; Hajós, G.; Dommisse, R. Tetrahedron. 2005, 61. 1571.
[9] Yang, S. W.; Abdel-Kader, M.; Malone, S.; Werkhoven, M.
C. M.; Jan, H. W.; Bursuker, I.; Neddermann, K.; Fairchild, C.;
Raventos-Suarez, C.; Menendez, A. T.; Lane, K.; David Kingston, G. I.
J. Nat. Prod. 1999, 62, 976.
[10] Guittat, L.; Alberti, P.; Rosu, F.; Van Miert, S.; Thetiot, E.;
Pieters, L.; Gabelica, V.; Pauw, D. E.; Ottaviani, A.; Riou, J. F.;
Mergny, J. L. Biochimie. 2003, 85, 535.
[11] Dassonviville, L.; Bonjean, K.; De Pauw-Gillet, M. C.;
Colson, P.; Houssier, C.; Quetin-Leclercq, J. A.; L.; Bailly, C.
Biochemistry. 1999, 38, 7719.
[12] Dhanabal, T.; Sangeetha, R.; Mohan, P. S. Tetrahedron.
2006, 62, 6258.
[13] Nandhakumar, R.; Suresh, T.; Mohan, P. S. Tetrahedron Lett.
2002, 43, 3327.
[14] Dhanabal, T.; Sangeetha, R.; Mohan, P. S. Tetrahedron Lett.
2005, 46, 4509.
[15] Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.;
Rombouts, G.; Pieters, L.; Haemers, A.; Dommisse, R. A. Synnlett.
2003, 5, 615.
[16] Zhang, X.; Campo Marino, A.; Larock, Y. T.; Richard, C.
Organic Letters. 2005, 7, 763.
7-(5-Cyclohexylpentyl)-5-methyl-7H-indolo[2,3-b]quino-
1
linium iodide (13). M.p 249-251 °C; H nmr (DMSO-d6): ꢀ
0.80-0.60 (m, 2H), 1.20-1.00 (m, 6H), 1.40-1.20 (m, 4H), 1.60-
1.42 (m, 5H), 2.00-1.80 (m, 2H), 4.60-4.80 (m, 5H), 7.60 (t, 1H,
J = 7.5 Hz), 7.90 (t, 1H, J = 8.4 Hz), 8.16-8.06 (m, 3H), 8.58 (m,
1h), 8.96 (d, 1H, J = 8.1 Hz), 9.20 (m, 1H),10.20 (s, 1H). Anal.
Calcd. for C27H33IN2. 1.8 H2O: C, 59.44; H, 5.96; N, 5.06.
Found: C, 59.52; H, 6.10; N, 5.14.
Acknowledgement. We gratefully acknowledge research
support from the National Institutes of Health, RCMI Grant No.
G12RR 03020, MBRS Grant # GM 08111, and Title III Grant to
Florida A&M University. The authors also thank Dr. Melissa
Jacob, Dr. Shabana Khan, Ms Marsha Wright and Mr John Trott
for conducting the antimicrobial and cytotoxicity testing, which
was supported by the NIH, NIAID, Division of AIDS, Grant No.
AI 27094, and the USDA Agricultural Research Service Specific
Cooperative Agreement No. 58-6408-2-0009. This work was
supported in part by the Pharmaceutical Research Center
NIH/NCRR 1 C06-RR12512-01 grant.
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[18] Wolfe, J. P.; Seble, W.; Marcoux, J. F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805.
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