Synthesis of homofascaplysin B, C and analogues by the photocyclization of 3-acyl-2-chloro-1-[2-(indol-3-yl)ethyl]indoles

Article abstract of DOI:10.1016/j.tet.2012.12.041

Two routes for the synthesis of homofascaplysin B, C and analogues have been established using the photocyclization as the key step. The first route is based on sequential photocyclization and photochemical dehydrogenation reactions of 2-chloro-3-acyl-1-[2-(indol-3-yl)ethyl]indoles in Cu(OAc)₂- and air-saturated acetone; and the second is based on the two-step reactions, namely, photocyclization of 2-chloro-3-acyl-1-[2-(indol-3-yl)ethyl]indoles in acetone and DDQ-mediated dehydrogenation of 13-acyl-6,7-dihydro-pyrido[1,2-a;3, 4-b′]diindoles in benzene at room temperature. Comparatively, the two-step route for the synthesis of homofascaplysin B, C and analogues is more efficient than the one-pot route.

Full text of DOI:10.1016/j.tet.2012.12.041

Accepted Manuscript
Synthesis of Homofascaplysin B, C and Analogues by the Photocyclization of 3-
Acyl-2-chloro-1-[2-(indol-3-yl)ethyl]indoles
Yisi Dai, Wenxue Zhang, Kongchen Wang, Weixia Wang, Wei Zhang
PII:
S0040-4020(12)01897-2
10.1016/j.tet.2012.12.041
TET 23853
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 September 2012
Revised Date: 16 December 2012
Accepted Date: 18 December 2012
Please cite this article as: Dai Y, Zhang W, Wang K, Wang W, Zhang W, Synthesis of Homofascaplysin
B, C and Analogues by the Photocyclization of 3-Acyl-2-chloro-1-[2-(indol-3-yl)ethyl]indoles, Tetrahedron
(2013), doi: 10.1016/j.tet.2012.12.041.
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Synthesis of Homofascaplysin B, C and Analogues
by the Photocyclization Reactions of
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3-Acyl-2-chloro-1-[2-(indol-3-yl)ethyl]indoles
Yisi Dai, Wenxue Zhang, Kongchen Wang, Weixia Wang, Wei Zhang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P.R. China.
hv
O
O
acetone O2
Cu(OAc)2
O
R2
Cl
R2
R3
N
R2
R3
N
R1
hv
R3
N
R1
R1
or
DDQ
benzene, r.t.
acetone
N
N
N
2
3
1

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of Homofascaplysin B, C and Analogues by the Photocyclization of 3-
Acyl-2-chloro-1-[2-(indol-3-yl)ethyl]indoles
Yisi Dai, Wenxue Zhang, Kongchen Wang, Weixia Wang, Wei Zhang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China. zhangwei6275@lzu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Two routes for the synthesis of homofascaplysin B, C and analogues have been
established using the photocyclization as the key step. The first route is based on sequential
photocyclization and photochemical dehydrogenation reactions of 2-chloro-3-acyl-1-[2-
(indol-3-yl)ethyl]indoles in Cu(OAc)2- and air-saturated acetone; and the second is based
on the two-step reactions, namely, photocyclization of 2-chloro-3-acyl-1-[2-(indol-3-yl)-
ethyl]indoles in acetone and DDQ-mediated dehydrogenation of 13-acyl-6,7-dihydro-
pyrido[1,2-a;3,4-b']diindoles in benzene at room temperature. Comparatively, the two-step
route for the synthesis of homofascaplysin B, C and analogues is more efficient than the
one-pot route.
Available online
Keywords:
homofascaplysin B, C
photocyclization
oxidative dehydrogenation
pyrido[1,2-a;3,4-b']diindole
2009 Elsevier Ltd. All rights reserved.
synthesis of homofascaplysin B and C.6 For example, Gribble
and co-workers reported the synthesis of homofascaplysin B and
1. Introduction
Fascaplysin, isolated in 1988 from the marine sponge
Fascaplysinopsis Bergquist sp., 1 exhibits a broad range of
bioactivities including antibacterial, antifungal, antiviral,
antimalarial, anticancer. 2 This compound has the novel 12H-
pyrido[1,2-a;3,4-b']diindole ring system, unprecedented amongst
natural products, but related to the relatively small group of
natural products having two indoles interconnected at their
respective C-2 positions, such as staurosporine and
rebeccamycin with indolo[2,3-a]pyrrolo[3,4-c]carbazole
structure.3 The analogues of fascaplysin, such as
C early in 1992. They provided a route to homofascaplysin B
and C by the oxidative cyclization of 1-(3-indoylethyl)indole,
Pd/C catalyzed dehydrogenation and formylation or oxalylation;
6a Dubovitskii completed the synthesis of homofascaplysin C by
Fischer cyclization between indoloketone and phenylhydrazine
and subsequent oxidation and dehydrogenation by DDQ; 6b
Vranken and co-workers reported the synthesis of
homofascaplysin C by the Brønsted acid catalyzed cyclization of
ditryptophan and oxidative cleavage of the amino acid; 6c
Waldmann and co-workers established a route to
homofascaplysin C by silver catalyzed and microwave assisted
condensation of 2-(phenylethynyl)benzaldehyde and tert-butyl 2-
(2-aminophenyl)acetate and then formylation. 6d But all these
methods have some disadvantages such as serious toxicity,
expensive and complexity. As a continuance of the synthesis of
polycyclic heterocyles by photocyclization reactions, 7 we want
to report here a concise and efficient synthesis of
homofascaplysin A, B and C, were discovered late in the Fijian
sponge F. reticulate,4 and also have potent biological activity
like antimicrobial activity and strong cytotoxicity against L-1210
mouse leukemia.2
O
OCH3
O
O
H
N
H
N
HO
H
O
N
+
+
N
N
N
Cl-
Cl-
homofascaplysin B, C and analogues by the photocyclization of
2-chloro-1-[2-(indol-3-yl)ethyl]-3-acylindoles and oxidative
dehydrogenation. Two routes to homofascaplysin C, B and
analogues have been established as shown in Scheme 1.
O
homofascaplysin B (III)
homofascaplysin A (II)
fascaplysin (I)
OCH2CH3
O
O
O
H
H
H
H
H
O
N
N
N
N
Br
R2
N
R3
N
R1
N
hv
O
N
N
3-bromohomofascaplysin C (VI)
homofascaplysin C (V)
homofascaplysin B-1 (IV)
R2
Cl
acetone
oxidant
R1
R3
3
N
O
N
O
Due to this fact, most of them are used to create novel anticancer
drugs. Many methods have been established for the synthesis of
fascaplysin,5 but only a few of reports have been found for the
R2
R3
N
R2
R3
R1
hv
DDQ
R1
1
N
acetone
pyridine
benzene
r.t.
R
R2
1 = H, Br, Me
N
= H, CO2Et, Me
R3 = H, Boc, Me
2
3
Scheme 1. Two routes for synthesis of homofascaplysin B, C and
analogues
* Corresponding author. E-mail: zhangwei6275@lzu.edu.cn;
1

ACCEPTED MANUSCRIPT
2
Tetrahedron
photocyclization /photochemical dehydrogenation reactions
seems not satisfactory for the synthesis of homofascaplysin B
and C, so another synthetic strategy is needed.
2. Results and Discussion
Initially, we attempted to synthesize homofascaplysin B, C and
analogues by a one-pot two-step reaction, namely
Table 1. Optimization of one-pot photocyclization/photochemical
dehydrogenation f 1a.
photocyclization / photochemical dehydrogenation of 2-chloro-
1-[2-(indol-3-yl)ethyl]-3-acylindoles (Scheme 1). Photochemical
dehydrogenation is an efficient and convenient method, and has
been used in the preparation of aromatics and alkenes. 8 The
Substrate 1a, which was prepared by the reaction of 2-
O
O
H
H
H
N
hv
H
N
Cl
acetone
N
N
or oxidant
chloroindole-3-carbaldehyde and 3-bromoethylindole, was
selected as the model substrate to sample the one-pot synthesis
of homofascaplysin C (3a), and acetone was selected as the
solvent and oxidative dehydrogenation agent because it was
reported that excited acetone could abstract hydrogen from
imdazolidines to produce imdazoles. 8d Irradiation at λ ꢀ280
nm of a deaerated anhydrous acetone and pyridine (5 mmol)
solution (100 ml) of 1a (1 mmol) at ambient temperature for 13
hours completely cleaned up the 1a to give two products
(Scheme 2).The addition of pyridine was to clean out HCl and
3a
1a
Time
(h)
13
Convn. d
(%)
Yield e
(%)
5
Entry
Solvent/additives
acetone a
1
2
98
a
25
100
30
acetone
acetone/10 % mol
3
4
5
25
25
25
100
100
100
35
48
42
benzophenone a
acetone/Cu(OAc)2/5 mmol
pyridine/airb
acetone/Cu(OAc)2/5 mmol
c
pyridine/O2
[a] Compound 1a (0.322 g, 1 mmol) was dissolved in anhydrous
acetone (100 mL) containing 5 mmol pyridine. The solution was
deaerated by bubbling Ar for half an hour and irradiated at λ ≥ 280
nm at ambient temperature.
retard the solution from turning dark during the irradiation.
hv
acetone
O
O
O
H
H
H
H
H
hv
N
[b] Air was pumped into the Cu(OAc)2-saturated acetone solution of
1a for ten minutes.
N
Cl
+
NH
N
acetone
pyridine
N
N
[c] The Cu(OAc)2-saturated acetone solution of 1a was bubbled with
oxygen for ten minutes.
2a main
3a minor
1a
[d] Conversion was calculated on the basis of 1a.
[e] Yield of isolated product based on 1a.
Scheme 2 Photoreaction of 1a in acetone
The main product was the photocyclization product 2a (75 %)
and the minor was the desired photocyclization/photochemical
dehydrogenation product homofascaplysin C (3a) (5 %). It was
found irradiation of the separated 2a under the same condition
lead to 3a slowly. These results indicated that the
Table 2. One-pot synthesis of homofascaplysin C, B and analogues by
photocyclization/photochemical dehydrogenation of 1a-f.[a]
O
O
R2
R2
R3
N
R1
R3
N
R1
hv
Cl
acetone
N
N
photocyclization of 1a seemed more quickly than the
Cu(OAc)2 O2
photochemical dehydrogenation of intermediate 2a, and
irradiation for a long time was needed to enhance the
3a-f
1a-f
Yield b
(%)
dehydrogenation reaction of 2a. Therefore, the irradiation of 1a
was performed under the same conditions for 25 hours, and in
this case, 3a was obtained in 30 % yield. In order to make further
increase of the yield of 3a, the photoreaction of 1a with the
addition of catalyst as benzophenone or chloranil in acetone was
tested, but no great improvement was observed. At last, the
photoreaction of 1a was carried out in a Cu(OAc)2- and air-
saturated acetone with the addition of pyridine (5 mmol) because
it was reported that Cu(OAc)2 could be used as an efficient agent
for the conversion of carbon radical to double bonds.8e, 9
Meantime, oxygen was needed in the procedure to regenerate
Cu(II) from Cu(I) because the solubility of Cu(OAc)2•H2O in100
mL acetone at 25 was only 0.42 mmol, not enough for the
reaction of 1.0 mmol 1a. In this case, the yield of 3a reached to
48 % after irradiation for 25 hours. The attempt to improve the
efficiency of this procedure by replacing air-saturated acetone
with oxygen-saturated acetone was failed because the yield of 3a
was decreased with the increase of the amount of the oxidation
products which might derived from the coupling of carbon
radicals with oxygen.10 Therefore, the photoreactions of other
substrates 1b-f were all carried out in the Cu(OAc)2- and air-
saturated acetone solution. All these reactions could afford the
photocyclization/photochemical dehydrogenation products 3a-f
in moderate yields (Table 1). All products were fully identified
by 1H NMR, 13C NMR and HRMS, and physical and spectral
data for our synthetic homofascaplysin B and C were in
agreement with those reported in the literature for the natural
products.2g, 4 However, the low efficiency of the one-pot
Entry
1
Substrate
Product
O
H
O
H
H
N
H
N
Cl
1a
1b
1c
1d
3a
3b
3c
3d
48
37
53
45
N
N
O
O
H
H
Boc
N
Boc
Cl
2
3
4
N
N
N
O
O
H
H
Br
H
H
Br
Cl
N
N
N
N
O
OMe
O
OMe
O
O
H
O
H
N
Cl
N
N
N
N
O
OEt
O
OEt
O
H
N
H
N
Cl
5
6
1e
1f
3e
3f
41
35
N
O
OEt
O
OEt
O
O
Me
N
Me
Cl
N
N
N
2

ACCEPTED MANUSCRIPT
3
O
O
[a] Compound 1a (0.322 g, 1 mmol) was dissolved in Cu(OAc)2-
and air-saturated acetone (100 mL). The solution was irradiated at λ
≥ 280 nm at ambient temperature for 25 hours.
H
H
H
N
hv
H
Cl
N
N
solvent/additive
N
[b] Yield of isolated product based on 1a.
2a
1a
We then designed to synthesize homofascaplysin B, C and
analogues (3) by a two-step reaction, namely, photocyclization
and DDQ-mediated dehydrogenation. DDQ-mediated
Entry
Solvent
CH2Cl2
CH3CN
Time (h) Convn. b (%) Yield c (%)
1
2
3
4
5
24
18
15
15
13
70
82
93
98
100
50
45
65
71
75
dehydrogenation is well known, and widely used in
aromatization of heterocycles.11 Firstly, we optimized the
photocyclization conditions of 1a. As indicated in Table 2,
irradiation of 1a in different deaerated solvents in Pyrex flask all
gave 2a as the main product, but the photoreaction in
CH2Cl2 +10ꢁacetone
acetone
acetone +1 % pyridine
[a] Compound 1a (0.322 g, 1 mmol) was dissolved in different
solvents (100 mL). The solution was deaerated by bubbling Ar for
half an hour and irradiated at λ ≥ 280 nm at ambient temperature.
[b] Conversion was calculated on the basis of 1a.
acetone/pyridine was obviously superior to that in other solvents.
This result may be ascribed to the photosensitization effect of
acetone, because the ET of acetone (ET = 326 kJ mol-1 12a is
)
[c] Yield of isolated product based on consumed 1a.
higher than that of indole-3-carbaldehyde (ET = 275 kJ mol-1).12b
Therefore acetone with addition of small quantity of pyridine
was selected as solvent for the photoreactions of substrate 1a-n.
Under the optimized condition, the photoreactions of all
substrates (1a-n) could afford the corresponding cyclization
products (2a-n) in moderate to high yields after the complete
conversion of the substrate 1a-n (Table 3). All products were
fully identified by 1H NMR, 13C NMR, HRMS and IR. The
structure of 2a was further confirmed by X-ray crystallography
(Figure 1).
Table 3. Optimization of photoreaction conditions for synthesis of
2a.a
Figure 1. X-ray crystal structure of 2a.
Table 4. Photocyclization of 2-chloro-1-[2-(1H-indol-3-yl)-ethyl]-3-acylindoles a
O
O
R2
R2
R3
N
R1
hv
R1
R3
N
Cl
acetone
pyridine
N
N
2
1
Yield b
(%)
Product
Yield b
(%)
Entry
Product
Entry
OEt
O
O
O
H
H
Me
N
H
N
Br
1
2a
2b
2c
2d
75
60
46
81
8
2h
61
60
55
52
N
N
O
O
H
H
H
Boc
N
H
N
Me
2
3
4
9
2i
2j
N
N
O
O
H
Me
N
H
Br
Me
Me
N
10
11
N
N
OMe
O
O
Boc
N
H
O
N
2k
N
N
3

ACCEPTED MANUSCRIPT
4
Tetrahedron
OEt
O
O
O
Me
H
N
H
N
5
2e
85
12
2l
72
N
N
OEt
Me
O
O
Me
Me
Me
N
O
6
7
2f
N
80
67
13
14
2m
2n
65
60
N
N
O
OEt
O
O
Boc
N
H
N
Br
2g
N
N
[a] The acetone solution (100 mL) of compound 1a-n (1 mmol) was deaerated by bubbling Ar for half an hour and irradiated at λ ≥ 280 nm at
ambient temperature for 13-15 hours until complete conversion of 1a-n.
[b] Yield of isolated product based on 1a-n.
7
8
9
2g
2k
2l
Br
CH3
H
COOEt
H
CH3
H
Boc
H
2
3
2
3g
3k
3l
87
89
92
It could be noticed from Table 4 that the yields of 2a-n was
influenced by the substituents on indolyl rings. For example, the
yields of products from 2a to 2b, 2e to 2f, 2i to 2k, and 2l to 2n
decreased gradually with the changes of substituents from
hydrogen, methyl to Boc group at nitrogen atom (Table 3, entries
1-2, 5-6, 9-11, 12-14). The effects were probably ascribed to the
increase of steric hindrance from hydrogen, methyl to Boc
groups. In addition, it was found that the substituent on the
phenyl ring, such as bromine and methyl group, made the yield
of 2c and 2g-k decreased as compared with those of 2a-b and 2d-
f (Table 3, entries, 3,7-11). These results might be derived from
the high reactivity of C-Br bond under irradiation and the
hydrogen-abstraction reactions of methyl with excited acetone
because more complex photoreaction mixtures were produced
from these substrates.
[a] Substrate 2a ( 0.5 mmol ) and DDQ (1.5 mmol ) in anhyd
benzene (20 mL) were stirred for 2-3 hours at room temperature.
[b] Yield of isolated product based on 2a-g and 2k-l.
A postulated mechanism for the formation of
homofascaplysin C (3a) from one-pot photoreaction of 2-chloro-
1-[2-(indol-3-yl)-ethyl]indole-3-carbaldehyde (1a) in Cu(OAc)2-
and air-saturated acetone is depicted in Scheme 3. First, acetone
sensitization lead 1a to becoming a diradical; the addition of the
diradical to another indole ring and subsequent dechlorination
give the intramolecular coupling product 2a; then, the abstraction
of hydrogen atom from 2a by excited acetone and subsequent
oxidation by Cu(OAc)2 afford the product 3a.
*
3
O
O
O
acetone
acetone*
H
H
H
Next, we performed the dehydrogenation of 2a-g and 2k-l by
DDQ to synthesize 3a-g and 3k-l (homofascaplysin B, C and
analogues). The dehydrogenation reaction of 2a was carried out
Cl
Cl
Cl
NH
NH
NH
N
N
N
1a
under different conditions, for example, in refluxing
O
O
6b
O
H
Cl
H
dichloromethane, in refluxing dioxane;
in refluxing benzene
H
H
-HCl
and in benzene at room temperature.9e The best result was
obtained from the reaction of 2a with 1.5 equivalent DDQ in
benzene at room temperature and the product 3a was obtained in
93 % yield. Then dehydrogenation of other selected substrates
was also conducted under the similar conditions. The reactions of
these substrates all afforded the expected aromatized products 3
in excellent yields (Table 5). Thus, the total efficiency of the
two-step reactions for synthesis of homofascaplysin B (3d),
Cl
H
N
H
H
N
N
N
N
N
2a
O
O
O
H
H
H
Cu(II)
acetone*
H
H
H
-H+
N
N
N
N
N
N
Cu(I)
O2
Cu(II)
.
OH
(AcO)2Cu
3a
.
Cu(II)
homofascaplysin B-1 (3e), homofascaplysin
C (3a) and
acetone
analogues was enhanced greatly as compared with that of the
one-pot synthesis of these compounds.
Scheme 3 A plausible photoreaction mechanism of 1a in Cu(OAc)2-
and air-saturated acetone.
Table 5 DDQ-mediated dehydrogenation of 6,7-dihydro-
pyrido[1,2-a;3,4-b']diindoles (2) a
3. Conclusion
O
O
R2
R3
N
R2
R3
N
R1
R1
In conclusion, two routes for the synthesis of homofascaplysin B,
C and analogues have been developed using the photoreaction as the
key step. The first route is based on sequential photocyclization and
photochemical dehydrogenation reactions of 2-chloro-3-acyl-1-[2-
(indol-3-yl)ethyl]indoles in Cu(OAc)2- and air-saturated acetone; the
second is based on the two-step reactions, namely, photocyclization
of 2-chloro-3-acyl-1-[2-(indol-3-yl)-ethyl]indoles in acetone and
DDQ-mediated oxidative dehydrogenation of 13-acyl-6,7-dihydro-
pyrido[1,2-a;3,4-b']diindoles. Comparatively, the two-step route for
the synthesis of homofascaplysin B, C and analogues is more
efficient than the one-pot route.
DDQ
benzene r.t.
N
N
2
3
Time
(h)
2
3
2
2
2
2
Entry Substrate
R1
R2
R3
Prod Yield (%) b
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
H
H
Br
H
H
H
H
H
H
H
Boc
H
3a
3b
3c
3d
3e
3f
93
90
92
88
85
91
COOMe
COOEt
COOEt
H
H
CH3
4

ACCEPTED MANUSCRIPT
5
solvent was removed under reduced pressure, the residue was
separated by column chromatography on silica gel eluted by
4. Experimental section
4.1 Experimental protocols:
hexane-ethyl acetate 20:1 (v/v) to afford product 2a
.
All reagents were purchased from commercial suppliers and
used without further purification. Flash chromatography was
carried out with silica gel (200-300 mesh). Analytical TLC was
performed with silica gel GF254 plates, and the products were
4.6 General procedure for the DDQ oxidative
dehydrogenation
DDQ (170.3 mg, 0.75 mmol) was added to a solution of
compound 2a (0.143 g, 0.5 mmol) in anhydrous benzene (20
mL).The mixture was stirred at room temperature for 2h. When
2a was consumed completely monitored by TLC, 20 mL
1
visualized by H NMR and 13C NMR (400 MHz and 100MHz,
respectively) spectra were recorded in CDCl3 or DMSO-d6.
Chemical shifts (
standard and spin-spin coupling constants (
The high resolution mass spectra (HRMS) were measured on a
Bruker Daltonics APEX 47e spectrometer by ESI. Mp data
δ
) are reported in ppm using TMS as internal
J
) are given in Hz.
saturated NaHCO3 solution was added. The resulting mixture was
extracted with CH2Cl2 (3 20 ml). The organic phase was washed
×
ꢂ
by water (20 mL) and dried over anhydrous Na2SO4. The residual
obtained by removing DCM was separated by column
chromatography on silica gel eluted by hexane-ethyl acetate 20:1
were measured with micro melting point apparatus. The X-ray
crystallographic analysis was performed with a Siemens SMART
CCD and a Siemens P4 diffractometer.
( v/v) to afford product 3a
.
12H-pyrido[1,2-a;3,4-b']diindole-13-carbaldehyde
(Homofascaplysin C) (3a)
4.2 General procedure for the preparation of 2-chloro-1-[2-
(1H-indol-3-yl)-ethyl]-1H-indole-3-carbaldehyde 7
Potassium carbonate (414 mg, 3.0 mmol) was added to a solution
Yellow solid; mp 250-251 ; 1HNMR (400 MHz, CDCl3):
δ 7.30
(t,
7.66 (d,
Hz, 1H), 8.06 (d,
(s, 1H), 12.13 (s, 1H); 13C NMR (100 MHz, CDCl3):
J
= 7.6 Hz, 1H), 7.38 (t,
= 8.0 Hz, 1H), 7.85 (d,
= 8.0 Hz, 1H), 8.17 (d,
J
= 7.2 Hz, 1H), 7.46-7.55 (m, 3H),
= 8.0 Hz, 1H), 8.00 (d, = 8.0
= 6.8 Hz, 1H), 10.16
105.38,
of 2-chloro-1
H-indole-3-carbaldehyde (322 mg, 1.0 mmol) and
J
J
J
3-(2-bromoethyl)-1
H-indole (446 mg, 2 mmol) in acetone (40
J
J
mL). The mixture was heated to reflux for 10h. When the starting
materials were consumed completely monitored by TLC, the
reaction mixture was concentrated by vacuum and then the
product was isolated by silica gel column chromatography to
give a yellow crystalline solid 1a. The identity and purity of the
product was confirmed by 1H and 13C NMR spectroscopic
analysis.
δ
107.81, 111.09, 112.56, 116.54, 117.54, 118.49, 120.20, 120.48,
122.10, 122.30, 125.45, 126.76, 129.25, 129.32, 131.87, 132.35,
138.01, 180.84; FT-IR (KBr, cm-1) 3432, 3251, 3047, 2922,
1722, 1658, 736; ESI-HRMS: m/z Calcd for C19H12N2O + Hꢃ:
285.1028, found 285.1020.
13-Formyl-pyrido[1,2-a;3,4-b']diindole-12-carboxylic acid
tert-butyl ester (3b)
4.3 General procedure for the preparation of 2-(2-chloro-1-
(indol-3-ylethyl)indol-3-yl)-2-oxo-acetic acid ethyl ester (1d)
NaH (24 mg, 1.0 mmol) was added to a solution of 2-(2-Chloro-
Yellow solid; mp 235-237 ; 1HNMR (400 MHz, CDCl3):
δ
1.68
= 8.4
= 8.4 Hz, 1H), 8.51
= 8.0 Hz, 1H), 10.30 (s, 1H); 13
27.91, 86.07, 102.15, 105.50,
(s, 9H), 7.41-7.47 (m, 3H), 7.54-7.60 (m, 2H), 7.91 (d,
Hz, 1H), 7.98 (d, = 7.6 Hz, 1H), 8.24 (d,
(d, = 6.8 Hz, 1H), 8.60 (d,
NMR (100 MHz, DMSO):
J
1-(2-indol-3-ylethyl)-1H-indol-3-yl)-2-oxo-acetic acid ethyl ester
J
J
(394 mg, 1.0 mmol) and 3-(2-bromo-ethyl)-1
H-indole (446 mg, 1
J
J
C
mmol) in THF (40 mL). The mixture was heated to reflux for 12h.
When the starting materials were consumed completely
monitored by TLC, the reaction mixture was concentrated by
vacuum and then the product was isolated by silica gel column
chromatography to give a yellow crystalline solid 1d. The
δ
107.37, 112.55, 114.12, 115.55, 120.86, 121.83, 123.11, 124.72,
124.87, 125.90, 126.53, 127.94, 129.30, 129.63, 132.19, 140.79,
151.27, 182.87; FT-IR (KBr, cm-1) 3441, 3247, 3047, 2981,
1732, 1657, 741; ESI-HRMS: m/z Calcd for C24H20N2O3 + Hꢃ:
385.1552, found 385.1557.
identity and purity of the product was confirmed by 1H and 13
NMR spectroscopic analysis.
C
2-Bromo-12H-pyrido[1,2-a;3,4-b']diindole-13-carbaldehyde
4.4 General procedure for the one-pot synthesis of
homofascaplysin B, C and analogues
Compound 1a (0.322 g, 1 mmol) was dissolved in 100 mL
(3c)
Yellow solid; mp 263-265 ; 1HNMR (400 MHz, CDCl3):
δ
7.34
= 6.8 Hz, 1H),
= 8.8 Hz, 1H), 8.04 (d, = 8.0
= 7.2 Hz, 1H), 10.14 (s, 1H), 12.12 (s, 1H);
13C NMR (100 MHz, DMSO):
110.24, 112.99, 113.12, 114.70,
(t,
7.70 (d,
Hz, 1H), 8.20 (d,
J
= 7.6 Hz, 1H), 7.48-7.56 (m, 2H), 7.64 (d,
J
Cu(OAc)2-saturated acetone containing 5 mmol pyridine and air
was pumped into the solution for ten minutes. The solution was
divided into two 50 mL Pyrex bottle and irradiated with a
medium-pressure mercury lamp (500 W) at ambient temperature
for 25 hours. Then solvent was removed under reduced pressure,
and the residue was separated by column chromatography on
silica gel eluted by hexane-ethyl acetate 20:1 ( v/v) to afford
product 3a and 2a. Physical and spectral data for our synthetic
products were in agreement with those reported in the literature
for the natural products.2c,4
J
= 8.4 Hz, 1H), 7.76 (d,
J
J
J
δ
115.53, 119.96, 120.61, 121.05, 121.18, 122.17, 122.55, 124.73,
125.00, 125.78, 126.60, 127.30, 131.97, 136.29, 184.98; FT-IR
(KBr, cm-1) 3438, 3256, 3072, 2961, 1725, 1657, 743; ESI-
HRMS: m/z Calcd for C19H11BrN2O + Hꢃ: 363.0133, found
363.0129.
2-(12H-Pyrido[1,2-a;3,4-b']diindol-13-yl)-2-oxoacetic acid
methyl ester (Homofascaplysin B) (3d)
4.5 General procedure for the photocyclization of 2-chloro-1-
(2-(indol-3-yl)ethyl)-3-indolecarbaldehydes
Yellow solid; mp 230-232 ; 1HNMR (400 MHz, CDCl3):
δ
4.12
= 7.6 Hz, 1H), 7.46 (t,
= 7.6 Hz, 1H), 7.64 (d, = 8.4 Hz, 1H),
7.69-7.73 (m, 2H), 7.88 (d, = 8.0 Hz, 1H), 8.06 (d, = 7.6 Hz,
1H), 8.30 (d,
= 7.2 Hz, 1H), 12.42 (s, 1H); 13C NMR (100
MHz, CDCl3): 52.74, 101.78, 108.89, 111.12, 112.60, 116.87,
(s, 3H), 7.32 (t,
J = 7.6 Hz, 1H), 7.38 (t, J
J
= 7.2 Hz, 1H), 7.53 (t,
J
J
Compound 1a (0.322 g, 1 mmol) was dissolved in 100 mL
anhydrous acetone containing 5 mmol pyridine. The solution was
deaerated by bubbling Ar for 30 min and irradiated at λ ≥ 280 nm
with a medium-pressure mercury lamp (500 W) at ambient
temperature until the disappearance of 1a. The progress of
reaction was monitored by TLC at regular intervals. After the
J
J
J
δ
119.49, 120.34, 120.43, 120.67, 121.73, 122.88, 126.13, 127.03,
127.41, 129.13, 133.14, 134.63, 138.27, 167.59, 177.74; FT-IR
5

ACCEPTED MANUSCRIPT
6
Tetrahedron
(KBr, cm-1) 3440, 3065, 1727, 1667, 1072, 619; ESI-HRMS:
FT-IR (KBr, cm-1) 3441, 3048, 2924, 1721, 741; ESI-HRMS:
m/z Calcd for C20H14N2O + Hꢃ: 299.1184, found 299.1182.
m/z Calcd for C21H14N2O3 + Hꢃ: 343.1083, found 343.1087.
2-(12H-Pyrido[1,2-a;3,4-b']diindol-13-yl)-2-oxoacetic acid
7,12-Dihydro-6H-pyrido[1,2-a;3,4-b']diinlole-13-
ethyl ester (Homofascaplysin B-1) (3e)
carbaldehyde (2a)
Yellow solid; mp 195-197 ; 1HNMR (400 MHz, CDCl3):
δ
1.50
= 7.2 Hz,
= 7.2 Hz, 1H), 7.56 (t,
= 8.4 Hz, 1H), 7.77-7.80 (m, 2H), 7.94 (d,
Yellow solid; mp 189-191 ; 1HNMR (400 MHz, CDCl3):
δ
3.40
= 7.2 Hz,
= 7.6 Hz, 1H), 7.54 (d, = 8.4
= 8.0 Hz, 1H), 7.97 (d, = 7.6 Hz, 1H), 10.34
(s, 1H), 11.57 (s, 1H); 13C NMR (100 MHz, CDCl3):
20.41,
(t,
1H), 7.43 (t,
6.8 Hz, 1H), 7.68 (d,
= 8.4 Hz, 1H), 8.10 (d,
1H), 12.53 (s, 1H); 13C NMR (150 MHz, CDCl3):
J
= 7.2 Hz, 3H), 4.60 (q,
J
= 7.2 Hz, 2H), 7.35 (t,
J
( t,
1H), 7.28-7.37 (m, 3H), 7.41 (d,
Hz, 1H), 7.61 (d,
J = 7.6 Hz, 2H), 4.42 (t, J = 7.6 Hz, 2H), 7.17 (t, J
J
= 7.2 Hz, 1H), 7.50 (t,
J
J
=
J
J
J
J
J
J
J
= 8.0 Hz, 1H), 8.38 (d,
J
= 7.2 Hz,
δ
δ
14.22, 62.11,
41.74, 109.93, 110.00, 111.76, 112.57, 117.52, 119.03, 120.27,
122.68, 123.67, 124.36, 125.68, 125.81, 128.53, 136.28, 136.59,
137.02, 183.88; FT-IR (KBr, cm-1) 3444, 3042, 2935, 1790,
1045,740; ESI-HRMS: m/z Calcd for C19H14N2O + Hꢃ: 287.1184,
found 287.1176.
101.83, 108.91, 111.13, 112.66, 116.91, 119.74, 120.31, 120.45,
120.71, 121.83, 122.89, 126.11, 127.17, 127.42, 129.29, 133.22,
134.81, 167.25, 178.30; FT-IR (KBr, cm-1) 3435, 3070, 2925,
1729, 1642, 1075, 615; ESI-HRMS: m/z Calcd for C22H16N2O3 +
Hꢃ: 357.1239, found 357.1241.
Crystal data for compound 2a (recrystallized from ethanol): C19
H14N2O, Mr = 286.32, Orthorhombic,
11.063(4) Å, = 18.364(6) Å, = 90.00 °,
colorless block, = 296 (2) K, space group
c = 1.370 g cm-3
P2(1)/c, = 4,
(MoK\a) = 0.71073 mm-1 , 2θmax = 51.00, 2573
reflection collected, 2125 unique (Rinit = 0.0506) which was used
a
= 6.832(2) Å ,
b =
c
β
V
= 1387.9(7) Å 3
,
2-(12-Methyl-12H-pyrido[1,2-a;3,4-b']diindol-13-yl)-2-
D
, T
oxoacetic acid ethyl ester (3f)
Yellow solid; mp 210-212 ; 1HNMR (400 MHz, CDCl3):
δ
1.31
= 7.2 Hz, 2H), 7.33-
= 7.2 Hz, 1H), 7.56-7.57 (m, 2H), 7.61 (d,
= 6.8 Hz, 1H), 7.89 (d, = 8.4 Hz, 1H), 8.04 (d, = 8.0 Hz,
= 8.0 Hz, 1H), 8.31 (d,
= 8.0 Hz, 1H); 13C NMR
13.94, 35.19, 62.11, 102.73, 107.57,
Z
ꢀ
(t,
J = 7.2 Hz, 3H), 4.00 (s, 3H), 4.43 (q, J
7.42 (m, 2H), 7.50 (t,
J
1H), 8.09 (d,
(100 MHz, CDCl3):
J
in all calculations. Final w
No. 896605.
R
(F2) = 0.0945 (all data). CCDC file
J
J
J
J
δ
13-Formyl-6,7-dihydro-pyrido[1,2-a;3,4-b']diindole-12-
carboxylic acid tert-butyl ester (2b)
110.73, 111.02, 117.52, 120.28, 120.51, 121.14, 121.49, 122.17,
122.65, 126.06, 127.19, 128.35, 132.10, 132.58, 133.75, 143.49,
165.84, 178.31; FT-IR (KBr, cm-1) 3435, 3064, 2926, 1717,
1598, 1075, 742; ESI-HRMS: m/z Calcd for C23H18N2O3 + Hꢃ:
371.1396, found 357.1392.
Yellow solid; mp 189-192 ; 1HNMR (400 MHz, CDCl3):
δ 1.61
(s, 9H), 3.17 (t,
7.37 (m, 4H), 7.44 (t,
8.18 (d,
13C NMR (100 MHz, CDCl3):
J
= 6.8 Hz, 2H), 4.40 (t,
J
= 6.8 Hz, 2H), 7.25-
J
= 7.6 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H),
J
= 8.4 Hz, 1H), 8.37 (d,
J = 8.0 Hz, 1H), 10.24 (s, 1H);
δ
21.68, 27.96, 40.13, 85.52,
108.94, 111.92, 116.02, 119.37, 122.11, 122.76, 123.19, 123.70,
123.92, 126.22, 126.75, 127.42, 128.36, 136.26, 136.33, 136.43,
150.21, 185.47; FT-IR (KBr, cm-1) 3437, 3052, 2983, 1736,
1091, 748; ESI-HRMS: m/z Calcd for C24H22N2O3 + Hꢃ:
387.1709, found 387.1705.
2-(2-Bromo-12H-pyrido[1,2-a;3,4-b']diindol-13-yl)-2-
oxoacetic acid ethyl ester (3g)
Yellow solid; mp 250-253 ; 1HNMR (400 MHz, CDCl3):
δ
1.54
= 7.6 Hz,
= 8.0 Hz, 1H), 7.56
= 8.0 Hz, 1H), 7.66-7.70 (m, 2H), 7.80 (s, 1H), 8.00 (d,
8.0 Hz, 1H), 8.20 (d,
= 6.8 Hz, 1H), 12.25 (s, 1H); 13C NMR
(100 MHz, CDCl3): 14.24, 62.34, 101.11, 109.16, 112.32,
(t,
1H), 7.41 (dd,
(d,
J
= 7.2 Hz, 3H), 4.62 (q,
J = 7.2 Hz, 2H), 7.30 (t, J
J
= 1.2, 8.4 Hz, 1H), 7.50 (t,
J
J
J =
J
δ
2-Bromo-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindole-13-
carbaldehyde (2c)
112.52, 116.71, 119.86, 120.48, 120.79, 121.60, 122.43, 125.64,
127.62, 128.48, 128.69, 131.68, 134.68, 138.29, 166.88, 178.02;
FT-IR (KBr, cm-1) 3436, 2926, 1723, 1635, 1069, 616; ESI-
HRMS: m/z Calcd for C22H15BrN2O3 + Hꢃ: 435.0344, found
435.0349.
Yellow solid; mp 233-236 ; 1HNMR (400 MHz, CDCl3):
δ
3.39
= 7.2 Hz,
= 1.6, 8.4 Hz, 1H), 7.53 (d,
= 8.0 Hz, 1H), 8.04 (s, 1H), 10.20 (s,
1H), 11.47 (s, 1H); 13C NMR (100 MHz, CDCl3):
20.33, 41.88,
(t,
1H), 7.29-7.35 (m, 2H), 7.41 (dd,
= 8.0 Hz, 1H), 7.60 (d,
J = 7.6 Hz, 2H), 4.38 (t, J = 7.6 Hz, 2H), 7.17 (t, J
J
J
J
δ
108.30, 109.35, 111.22, 112.20, 112.47, 112.62, 112.65, 119.13,
120.24, 120.32, 124.69, 125.19, 126.50, 127.11, 135.77, 136.75,
183.43; FT-IR (KBr, cm-1) 3438, 3256, 3072, 2961, 1725, 1657,
743; ESI-HRMS: m/z Calcd for C19H13BrN2O + Hꢃ: 365.0289,
found 365.0281.
13-Formyl-2-methyl-pyrido[1,2-a;3,4-b']diindole-12-
carboxylic acid tert-butyl ester (3k)
Yellow solid; mp 242-243 ; 1HNMR (400 MHz, CDCl3):
δ
1.67
= 8.8 Hz, 1H), 7.41-7.46 (m, 2H),
= 8.0 Hz, 1H), 7.68 (d, = 8.4 Hz, 1H), 7.96 (d, = 7.6
Hz, 1H), 8.23 (d, = 7.6 Hz, 1H), 8.41 (s, 1H), 8.45 (d, = 6.8
Hz, 1H), 10.27 (s, 1H); 13C NMR (150 MHz, CDCl3):
21.86,
(s, 9H), 2.58 (s, 3H), 7.24 (d,
7.57 (t,
J
J
J
J
J
J
2-(7,12-Dihydro-6H-pyrido[1,2-a;3,4-b']diindol-13-yl)-2-
δ
oxoacetic acid methyl ester (2d)
28.03, 85.97, 104.31, 107.84, 109.88, 110.81, 112.61, 115.98,
120.19, 122.19, 124.22, 124.38, 124.88, 125.28, 126.75, 128.31,
128.80, 130.28, 136.25, 141.24, 150.17, 183.52; FT-IR (KBr, cm-
1) 3439, 3058, 2941, 1738, 760; ESI-HRMS: m/z Calcd for
C25H22N2O3 + Hꢃ: 399.1709, found 399.1708.
Yellow solid; mp 186-187 ; 1HNMR (400 MHz, CDCl3):
(t, J = 7.6 Hz, 2H), 4.09 (s, 3H), 4.45 (t, J
δ
3.42
= 7.6 Hz, 2H), 7.18 (t,
= 7.2 Hz, 1H), 7,25-7.37 (m, 3H), 7.43 (d, = 8.0 Hz, 1H),
7.51-7.54 (m, 2H), 7.63 (d,
= 8.0 Hz, 1H), 11.64 (s, 1H); 13
NMR (100 MHz, CDCl3): 20.26, 41.92, 52.87, 106.36, 110.03,
J
J
J
δ
C
112.63, 113.19, 119.16, 119.19, 120.46, 123.25, 123.99, 124.83,
125.15, 125.56, 126.08, 136.70, 137.36, 139.99, 166.85, 180.90;
FT-IR (KBr, cm-1) 3438, 3062, 2930, 1736, 1651, 1061, 745;
ESI-HRMS: m/z Calcd for C22H18N2O3 + Hꢃ: 345.1239, found
345.1232.
13-Acetyl-12H-pyrido[1,2-a;3,4-b']diindole (3l)
Yellow solid; mp 244-247 ; 1HNMR (400 MHz, DMSO):
δ
2.85 (s, 3H), 7.31 (t,
7.94 (m, 2H), 8.14 (d,
8.42 (d, = 8.4 Hz, 1H), 8.91 (d,
13C NMR (100 MHz, DMSO):
J
= 7.2 Hz, 1H), 7.42-7.58 (m, 3H), 7.91-
= 8.4 Hz, 1H), 8.22 (d, = 8.0 Hz, 1H),
= 7.2 Hz, 1H), 12.64 (s, 1H);
31.75, 106.21, 107.81, 112.70,
J
J
J
J
δ
2-(7,12-Dihydro-6H-pyrido[1,2-a;3,4-b']diindol-13-yl)-2-
113.50, 118.39, 118.71, 120.71, 120.86, 121.16, 122.15, 122.24,
125.84, 126.76, 127.49, 128.64, 132.56, 132.76, 137.77, 192.28;
oxoacetic acid ethyl ester (2e)
6

ACCEPTED MANUSCRIPT
7
Yellow solid; mp 183-185 ; 1HNMR (400 MHz, DMSO):
δ
Yellow solid; mp 184-185 ; 1HNMR (400 MHz, CDCl3):
2.51 (s,3H), 3.24 (t, = 6.8 Hz, 2H), 3.95 (s, 3H), 4.27 (t,
Hz, 2H), 7.10 (d, = 8.0 Hz, 1H), 7.17-7.29 (m, 2H), 7.37 (t,
7.2 Hz, 1H), 7.45 (d, = 8.0 Hz, 1H), 7.62 (d, = 6.4 Hz, 1H),
8.25 (s, 1H), 10.32 (s, 1H); 13C NMR (100 MHz, CDCl3):
21.51, 27.96, 40.18, 85.50, 108.58, 111.67, 116.04, 119.31,
δ
1.36 (t,
4H), 7.14(t,
Hz, 1H), 7.46 (d,
1H); 13C NMR (100 MHz, DMSO):
J
= 6.8 Hz, 3H), 3.39 (t,
J
= 7.6 Hz, 2H), 4.50-4.58 (m,
J
J = 6.8
J
= 7.6 Hz, 1H), 7.23-7.32 (m, 2H), 7.38 (t,
= 8.0 Hz, 1H), 7.70-7.76 (m, 3H), 11.54 (s,
14.34, 19.93, 42.03, 62.55,
J
= 7.2
J
J =
J
J
J
δ
δ
105.47, 111.78, 113.61, 114.77, 118.67, 119.88, 120.63, 123.61,
124.35, 124.80, 124.94, 125.63, 137.12, 137.62, 139.42, 166.74,
181.00; FT-IR (KBr, cm-1) 3437, 3052, 2925, 1734, 1056, 739;
ESI-HRMS: m/z Calcd for C22H18N2O3 + Hꢃ: 359.1396, found
359.1399.
121.89, 122.12, 122.93, 123.69, 124.71, 125.44, 126.68, 127.46,
128.48, 132.52, 134.76, 139.45, 185.59; FT-IR (KBr, cm-1) 3442,
3042, 2930, 1728, 1127, 756; ESI-HRMS: m/z Calcd for
C21H18N2O + Hꢃ: 315.1497, found 315.1494.
2-(12-Methyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindol-13-
13-Formyl-2-methyl-6,7-dihydro-pyrido[1,2-a;3,4-b']diindole-
12-carboxylic acid tert-butyl ester (2k)
yl)-2-oxoacetic acid ethyl ester (2f)
Yellow solid; mp 172-174 ; 1HNMR (400 MHz, CDCl3):
δ
1.20
= 6.4 Hz, 2H), 3.74 (s, 3H), 4.26-
4.33 (m, 4H), 7.20-7.37 (m, 4H), 7.40-7.44 (m, 2H), 7.65 (d,
8.0 Hz, 1H), 7.93 (d,
= 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): 13.77, 21.29, 33.79, 41.44, 62.19, 107.41, 109.64,
Yellow solid; mp 182-184 ; 1HNMR (400 MHz, CDCl3):
δ
1.59
= 6.8 Hz,
= 8.8 Hz, 1H), 7.32 (t,
= 7.6 Hz, 1H),
(t,
J
= 7.2 Hz, 3H), 3.29 (t,
J
(s, 9H), 2.48 (s, 3H), 3.14 (t,
2H), 7.14 (d, = 8.4 Hz, 1H), 7.24 (d,
= 7.2 Hz, 1H), 7.43 (t, = 7.2 Hz, 1H), 7.57 (d, J
J = 6.8 Hz, 2H), 4.36 (t, J
J
=
J
J
J
J
J
δ
8.17-8.19 (m, 2H), 10.19 (s, 1H); 13C NMR (100 MHz, CDCl3):
21.49, 21.65, 27.94, 40.14, 85.46, 108.58, 111.62, 115.99,
119.30, 121.85, 122.95, 123.67, 125.41, 126.33, 126.65, 127.43,
128.42, 132.47, 134.73, 136.36, 139.41, 150.19, 185.55; FT-IR
δ
110.80, 114.67, 119.44, 120.43, 120.71, 122.99, 123.86, 124.20,
125.36, 127.01, 130.41, 136.03, 136.56, 140.96, 165.03, 180.90;
FT-IR (KBr, cm-1) 3437, 3057, 2927, 1738, 1057, 741; ESI-
HRMS: m/z Calcd for C23H20N2O3 + Hꢃ: 373.1552, found
373.1557.
(KBr, cm-1) 3448, 3051, 2978, 1737, 1149, 763; ESI-HRMS: m/z
Calcd for C25H24N2O3 + Hꢃ: 401.1865, found 401.1869.
2-(2-Bromo-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindol-13-
13-Acetyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindole (2l)
Yellow solid; mp 197-198 ; 1HNMR (400 MHz, CDCl3):
δ
2.85
= 7.2 Hz, 2H), 7.15 (t,
= 7.2 Hz, 1H), 7.25-7.53 (m, 3H), 7.42 (dd, = 1.6, 7.2 Hz,
1H), 7.51 (d, = 8.4 Hz, 1H), 7.60 (dd, = 0.8, 7.6 Hz, 1H), 7.93
(dd,
= 1.6, 7.2 Hz, 1H), 11.99 (s, 1H); 13C NMR (100 MHz,
CDCl3): 20.30, 31.79, 41.75, 109.85, 111.73, 111.77, 112.47,
yl)-2-oxoacetic acid ethyl ester (2g)
Yellow solid; mp 220-221 ; 1HNMR (400 MHz, CDCl3):
δ
1.50
= 7.6 Hz,
= 8.0 Hz, 1H), 7.29-7.35
= 2.0, 8.4 Hz, 1H), 7.51 (d, = 8.4 Hz, 1H),
= 8.0 Hz, 1H), 7.70 (s, 1H), 11.60 (s, 1H); 13C NMR
(100 MHz, CDCl3): 14.15, 20.18, 42.05, 62.52, 105.79, 111.21,
(s, 3H), 3.35 (t, J = 7.2 Hz, 2H), 4.39 (t, J
(t,
2H), 4.58 (q,
(m, 2H), 7.43 (dd,
7.63 (d,
J
= 7.2 Hz, 3H), 3.42 (t,
J
= 7.6 Hz, 2H), 4.42 (t,
J
J
J
J
= 7.2 Hz, 2H), 7.19 (t,
J
J
J
J
J
J
J
δ
δ
118.82, 120.03, 120.87, 122.35, 123.02, 123.96, 125.76, 126.16,
127.02, 136.20, 137.09, 137.26, 194.87; FT-IR (KBr, cm-1) 3442,
3046, 2920, 1755, 1467, 736; ESI-HRMS: m/z Calcd for
C20H16N2O + Hꢃ: 301.1341, found 301.1345.
112.64, 113.55, 116.55, 119.28, 120.58, 122.23, 124.73, 125.10,
125.49, 126.79, 127.74, 136.10, 136.83, 140.51, 166.17, 181.01;
FT-IR (KBr, cm-1) 3437, 3069, 2921, 1727, 1058, 730; ESI-
HRMS: m/z Calcd for C22H17BrN2O3 + Hꢃ: 437.0501, found
437.0507.
13-Acetyl-1-12-methyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-
b']diindole (2m)
Yellow solid; mp 195-197 ; 1HNMR (400 MHz, CDCl3):
δ
2.68
= 6.8 Hz,
= 8.0 Hz, 1H), 7.39-7.43 (m,
= 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
21.36, 30.92, 33.64, 41.22, 109.39, 110.68, 112.83, 113.74,
2-(2-Bromo-12-methyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-
b']diindol-13-yl)-2-oxoacetic acid ethyl ester (2h)
(s, 3H), 3.24 (t,
2H), 7.18-7.34 (m, 4H), 7.63 (d,
2H), 8.08 (d,
J = 6.8Hz, 2H), 3.73 (s, 3H), 4.22 (t, J
Yellow solid; mp 118-121 ; 1HNMR (400 MHz, CDCl3):
δ
1.18
= 6.4 Hz, 2H), 3.70 (s, 3H), 4.22-
4.30 (m, 4H), 7.20-7.26 (m, 2H), 7.35 (t, = 6.8 Hz, 1H), 7.39-
7.43 (m, 2H), 7.64 (d,
= 8.0 Hz, 1H), 8.10 (s, 1H); 13C NMR
(100 MHz, CDCl3): 13.72, 21.19, 33.71, 41.55, 62.37, 106.81,
J
(t,
J
= 6.8 Hz, 3H), 3.28 (t,
J
J
δ
J
J
119.12, 120.47, 121.06, 122.11, 123.18, 123.56, 125.58, 126.76,
130.53, 132.82, 136.29, 140.50, 195.06; FT-IR (KBr, cm-1) 3437,
3052, 2944, 1721, 1143, 742; ESI-HRMS: m/z Calcd for
C21H18N2O + Hꢃ: 315.1497, found 315.1500.
δ
110.80, 110.88, 115.05, 116.29, 119.55, 120.85, 123.18, 124.50,
125.26, 126.73, 128.61, 130.01, 135.25, 136.60, 141.07, 164.46,
180.59; FT-IR (KBr, cm-1) 3442, 3057, 2933, 1732, 1057, 741;
ESI-HRMS: m/z Calcd for C23H19BrN2O3 + Hꢃ: 451.0657, found
451.0658.
13-Acetyl-6,7-dihydro-pyrido[1,2-a;3,4-b']diindole-12-
carboxylic acid tert-butyl ester (2n)
Yellow solid; mp 171-173 ; 1HNMR (400 MHz, CDCl3):
δ
1.61
(s, 9H), 3.17 (t,
7.38 (m, 4H), 7.44 (t,
8.18 (d,
13C NMR (100 MHz, CDCl3):
δ
108.94, 111.92, 116.02, 119.37, 122.11, 122.76, 123.19, 123.70,
123.92, 126.22, 126.75, 127.42, 128.36, 136.26, 136.33, 139.43,
150.21, 185.47; FT-IR (KBr, cm-1) 3431, 3052, 2927, 1744,
1143, 742; ESI-HRMS: m/z Calcd for C25H24N2O3 + Hꢃ:
401.1865, found 401.1868.
J
= 6.8 Hz, 2H), 4.40 (t,
J
= 6.8 Hz, 2H), 7.25-
2-Methyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindole-13-
J
= 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H),
carbaldehyde (2i)
Yellow solid; mp 191-193 ; 1HNMR (400 MHz, CDCl3):
δ
2.51
= 7.6 Hz, 2H), 7.15-
= 8.4 Hz, 1H), 7.61
J
= 8.4 Hz, 1H), 8.37 (d,
J = 8.0 Hz, 1H), 10.23(s, 1H);
21.68, 27.96, 40.13, 85.52,
(s, 3H), 3.39 (d,
7.18 (m, 2H), 7.28-7.32 (m, 2H), 7.54 (d,
(d,
NMR (100 MHz, DMSO):
J
= 7.6 Hz, 2H), 4.40 (d,
J
J
J
= 8.0 Hz, 1H), 7.75 (s, 1H), 10.27 (s, 1H), 11.57 (s, 1H); 13
C
δ
20.24, 21.68, 41.56, 110.58, 113.02,
113.48, 119.71, 119.95, 120.15, 120.46, 124.32, 125.48, 125.53,
125.63, 125.89, 127.08, 132.05, 135.78, 137.45, 138.09, 184.59;
FT-IR (KBr, cm-1) 3441, 3047, 2954, 1736, 1081, 741; ESI-
HRMS: m/z Calcd for C20H16N2O + Hꢃ: 301.1341, found
301.1343.
Acknowledgements
We thank the National Natural Science Foundation of China
(Grant Nos. 20872056 and J1103307) for financial support.
2,12-Dimethyl-7,12-dihydro-6H-pyrido[1,2-a;3,4-b']diindole-
13-carbaldehyde (2j)
References:
7

ACCEPTED MANUSCRIPT
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Supplementary Material
.
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.
.
,
,
,
8