Synthesis of 4-azachromeno[2,3-b]indol-11(6H)-one and its derivatives as analogues of ellipticine

Article abstract of DOI:10.3987/COM-08-S(S)3

4-Azachromeno[2,3-b]indol-11(6H)-ones (4) and their derivatives (5) as analogues of ellipticine were synthesized through a straightforward, two or three-step process. Tetracyclic heterocycles (4) were obtained by facile cyclization of indolin-2-ones (2) or (3) and 2-chloronicotinoyl chloride under the condition of the 'Jensen'-reaction. Alkylation of the compounds (4) afforded 6-substituted 4-azachromeno[2,3-b]indol-ll(6H)-ones.

Full text of DOI:10.3987/COM-08-S(S)3

HETEROCYCLES, Vol. 80, No. 1, 2010
251
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 251 - 258. © The Japan Institute of Heterocyclic Chemistry
Received, 17th December, 2008, Accepted, 26th January, 2009, Published online, 2nd February, 2009
DOI: 10.3987/COM-08-S(S)3
SYNTHESIS OF 4-AZACHROMENO[2,3-b]INDOL-11(6H)-ONE AND ITS
DERIVATIVES AS ANALOGUES OF ELLIPTICINE
Yanhong Chen, Chunhao Yang,* and Yuyuan Xie*
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica,
SIBS, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203
P.R.China; e-mail: chunhao_yang70@hotmail.com
Abstract – 4-Azachromeno[2,3-b]indol-11(6H)-ones (4) and their derivatives (5)
as analogues of ellipticine were synthesized through a straightforward, two or
three-step process. Tetracyclic heterocycles (4) were obtained by facile
cyclization of indolin-2-ones (2) or (3) and 2-chloronicotinoyl chloride under the
condition of the ‘Jensen’-reaction. Alkylation of the compounds (4) afforded
6
-substituted 4-azachromeno[2,3-b]indol-11(6H)-ones.
INTRODUCTION
Ellipticine (1), isolated from the leaves of Ochrosia elliptica Labill (family Apocynaceae), was
1
-3
discovered to have antitumor activities in 1967. Its mechanism of action was considered to be based
4, 5
mainly on DNA intercalation or the inhibition of topoisomerase II.
development was limited by poor drug solubility and in vivo host toxicities such as hemolytic activity,
Nevertheless, its early clinical
6
, 7
decreased heart rate and hepatotoxicity.
In view of that, many interests have been focused on
modification of the structure of ellipticine to improve its solubility and reduce the side effects. Many
analogues of ellipticine had been reported; the compounds, however, are simply a replacment of
functional groups at the l-, 2-, 5-, 6-, 9- and 11-positions, or an addition of a nitrogen atom on the
8
, 9
9, 10
tetracyclic skeleton. The change of core structure of ellipticine was reported only by few literatures.

252
HETEROCYCLES, Vol. 80, No. 1, 2010
1
10
11
2
9
N
A
C
D
4
B
N
H
3
8
5
6
7
1. ellipticine
Therefore, we synthesized 4-azachromeno[2,3-b]indol-11(6H)-ones which replaced C nucleus of
ellipticine with 4H-pyran-4-one via the reaction of indolin-2-ones with 2-chloronicotinoyl chloride under
1
1
the condition of the ‘Jensen’-reaction (calcium hydroxide, refluxing, 1,4-dioxane). The compounds with
novel structure could be regarded as the analogues of ellipticine merging the heterocyclic frameworks of
both ellipticine and isoflavone. As it had been demonstrated that addition of a basic side chain to the
1
2
ellipticine structure could improve DNA binding property, it prompted us to introduce a basic side chain
to 4-azachromeno[2,3-b]indol-11(6H)-ones. Herein, we describe the convenient synthesis of
4
-azachromeno[2,3-b] indol-11(6H)-one derivatives as novel antitumor agents.
RESULTS AND DISCUSSION
A facile two or three-step process for the preparation of 4-azachromeno[2,3-b]indol-11(6H)-ones and
their derivatives were reported in Scheme 1. Compounds (2a) and (2b) were acetylated with acetic
anhydride under reflux. The acetylated products (3a) and (3b) were then annulated with
13
2
-chloronicotinoyl chloride which was prepared according to the known procedure under the conditions
of DMAP in refluxing THF or Ca(OH) in refluxing 1,4-dioxane (the ‘Jensen’-reaction condition) to gain
2
4
-azachromeno[2,3-b]indol-11(6H)-one (4a) and 9-chloro-4-azachromeno[2,3-b]indol-11(6H)-one (4b)
respectively. The protecting group was removed simultaneously during the annulation. However, the
reaction under the former conditions completed after 24 h and the product needed to be purified by
column chromatography on silica gel. The latter could be completed in shorter time and the pure products
were obtained easily by dilution of the reaction mixture with water, filtration, washing and drying. Finally,
the desired derivatives (5a-5f) of (4a) or (4b) were obtained by alkylation with corresponding alkyl halide
2 3
using K CO as base and DMF or acetone as solvent.
For the synthesis of 9-nitro-4-azachromeno[2,3-b]indol-11(6H)-one (4c), 5-nitroindolin-2-one was
1
4
prepared by nitration of indolin-2-one according to the literature. The product of acetylation of
-nitroindolin-2-one was not 1-acetyl-5-nitroindolin-2-one but triacetyl compound (3c). Considering the
5
potent electron-withdrawing nitro group, 2-chloronicotinoyl chloride might attack C-3 easier than N-1.
Experiments proved our prediction and (4c) was obtained without any protecting groups. In order to get

HETEROCYCLES, Vol. 80, No. 1, 2010
253
reduced product of compound (4c), various procedures were examined including Pd/C, H
2
in DMF, 15%
TiCl
3
in AcOH/H
2
O, Fe/NH
4
Cl in MeOH/H
2
O and so on, but all cases did not succeed.
O
R1
Ac O
R1
2-chloronicotinoyl chloride
R1
2
DMAP, THF or Ca(OH) , dioxane
2
N
O
N
N
O
N
O
H
H
Ac
2a-b
4a-b
3a-b
2
2
a: R =H
3a: R =H
1
1
4a: R =H
1
b: R =Cl
3b:R =Cl
1
1
4b: R =Cl
1
5
5
a: R =H, R =Me; 5b: R =H, R =Et;
1 2 1 2
O
O
c: R =H; R =CH CH NH ;
1
2
2
2
2
K CO
R1
5d: R1
=H, R =CH CH NMe ;
2
2
2
2
2
3
DMF or acetone
N
N
N
5
e: R =H, R =
;
1
2
R2
N
5
f: R =Cl, R =
5a-f
1
2
Ac
O N
O N
2
2
Ac O
2
N
O
N
OAc
H
Ac
2c
3c
O
O
O N
2
2
-chloronicotinoyl chloride
Ca(OH) , dioxane
2
N
N
H
4c
Scheme 1
To verify whether it was necessary to protect nitrogen atom when indolin-2-one (2a) or
-chloroindolin-2-one (2b) reacted as starting material, indolin-2-one was reacted with 2-chloronicotinoyl
chloride directly under the same condition which was illustrated in Scheme 2.
-Azachromeno[2,3-b]indol-11(6H)-one was also obtained with unprotected indolin-2-one in a much
5
4
lower yield (yield: 4.2%).
Unfortunately, 4-chloronicotinoyl chloride failed to give the corresponding product with compound (3a)
under those conditions described above.

254
HETEROCYCLES, Vol. 80, No. 1, 2010
O
O
2
-chloronicotinoyl chloride
Ca(OH) , dioxane
N
O
2
N
N
H
H
4a
2a
Scheme 2
In conclusion, we established a convenient procedure for the synthesis of 4-azachromeno[2,3-b]indol-
1(6H)-one and its derivatives. Some of them display potent antitumor activities and will be reported
1
elsewhere.
EXPERIMENTAL
Chemical reagents were commercial products and used without purification in all cases. Solvents were
1
dried by standard methods. The H NMR spectra were recorded by GEMINI spectrometer at 300 MHz.
MS and HRMS spectra were recorded on a MAT-95 spectrometer. Melting points were measured by
Büchi 510 melting point apparatus and were uncorrected.
1
-Acetylindolin-2-one (3a)
The suspension of indolin-2-one (1 g, 7.5 mmol) in 5 mL of acetic anhydride was heated under reflux for
h. After cooling, the resulted pink precipitate was filtered, washed with cold water and dried. Yield: 775
4
15
1
mg (58.9%); mp 120-122°C (lit., mp 125-126°C); H NMR (300MHz, DMSO-d
Hz, Ar-H ), 7.32 (2H, m, Ar-H), 7.19 (1H, td, J=7.5, 1.1 Hz, Ar-H), 3.82 (2H, s, CH
-Acetyl-5-chloroindolin-2-one (3b)
6
): δ 8.07 (1H, d, J=8.3
2
), 2.56 (3H, s, CH ).
3
1
Compound (3b) was prepared in the same way as (3a) from 5-chloroindolin-2-one (1 g, 6.0 mmol) and 5
1
mL of acetic anhydride to give brown precipitate. Yield: 653 mg (51.9%); mp 125-127°C; H NMR
(
300MHz, CDCl ): δ 8.17 (1H, d, J=8.4 Hz, Ar-H), 7.27 (1H, d, J=8.4 Hz, Ar-H), 7.26 (1H, s, Ar-H ),
3
+
3
.71 (2H, s, CH
HRMS (EI) calcd. for C10
,3-Diacetyl-5-nitro-1H-indol-2-yl acetate (3c)
Compound (3c) was prepared in the same way as (3a) from 5-nitroindolin-2-one (400 mg, 2.2 mmol) and
2
), 2.67 (3H, s, CH
3
); MS (EI) m/z (%): 211 (M+2, 6), 209 (M , 20), 167 (100), 169 (33).
H
8
2
ClNO , 209.0244; found 209.0244.
1
5
mL of acetic anhydride. After cooling and adding 20 mL of water, the resulting yellow precipitate was
1
filtered, washed with EtOAc and dried. Yield: 154 mg (22.5%); mp 144-146°C; H NMR (300MHz,
CDCl
3
): δ 8.51 (1H, d, J=2.5 Hz, Ar-H), 8.45 (1H, d, J=9.1 Hz, Ar-H), 8.24 (1H, dd, J=9.1, 2.5 Hz,
+
Ar-H ), 2.77 (3H, s, CH ), 2.76 (3H, s, CH ), 2.51 (3H, s, CH ); MS (EI) m/z (%): 304 (M , 5), 262 (50),
3
3
3
2
20 (100), 205 (25). HRMS (EI) calcd. for C14
H
12
N
2
O
6
, 304.0695; found 304.0694.

HETEROCYCLES, Vol. 80, No. 1, 2010
255
4
-Azachromeno[2,3-b]indol-11(6H)-one (4a)
Method A: A mixture of 1-acetylindolin-2-one (205 mg, 1.17 mmol), 2-chloronicotinoyl chloride (207
mg, 1.17 mmol) and DMAP (276 mg, 2.26 mmol) in 5 mL of dry THF was heated under reflux for 24 h.
The crude product was purified by column chromatography on silica gel (CH
9 mg (35.8%).
Method B: Under anhydrous conditions, to a suspension of 1-acetylindolin-2-one (4.976 g, 28.4 mmol)
and Ca(OH) (4.208 g, 56.8 mmol) in 40 mL of dry 1,4-dioxane, a solution of 2-chloronicotinoyl chloride
5.2 g, 29.7 mmol) in 15 mL of dry 1,4-dioxane was added. The reaction mixture was heated at reflux for
2 2
Cl /EtOAc, 7/1, v/v). Yield:
9
2
(
1
5 h under stirring. After cooling to rt, the mixture was treated with 114 mL of 2 N HCl, stirred for 15
min, and poured into 100 mL of H
2
2
O. After 30 min, the pink solid was filtered off, washed with H O and
1
dried. Yield: 3.036 g (45.2%); mp＞300°C; H NMR (300MHz, DMSO-d ): δ 13.24 (1H, s, NH), 8.74
6
(1H, dd, J=4.8, 2.2 Hz, Ar-H), 8.69 (1H, dd, J=7.5, 2.2 Hz, Ar-H), 8.10 (1H, dd, J=7.1, 1.9 Hz, Ar-H),
+
7
1
.69 (1H, m, Ar-H), 7.55 (1H, dd, J=6.9, 1.2 Hz, Ar-H), 7.34 (2H, m, Ar-H); MS (EI) m/z (%): 236 (M ,
8 2 2
00), 208 (18), 179 (33). HRMS (EI) calcd. for C14H N O , 236.0585; found 236.0590.
Method C: Compound (4a) was also prepared in the same way as method B from indolin-2-one (133 mg,
mmol), Ca(OH) (148 mg, 2 mmol), and 2-chloronicotinoyl chloride (175 mg, 1 mmol). The crude
product was purified by column chromatography on silica gel (CH Cl /MeOH, 50/1, v/v). Yield: 10 mg
4.2%)
-Chloro-4-azachromeno[2,3-b]indol-11(6H)-one (4b)
Compound (4b) was prepared in the same way as method B from 1-acetyl-5-chloroindolin-2-one (209 mg,
1
2
2
2
(
9
1
mmol), Ca(OH)
2
(148 mg, 2 mmol), and 2-chloronicotinoyl chloride (175 mg, 1 mmol) to give gray
1
solid. Yield: 167 mg (61.8%); mp＞300°C; H NMR (300MHz, DMSO-d
6
): δ 13.28 (1H, s, NH), 8.75
(
1H, dd, J=4.7, 2.1 Hz, Ar-H), 8.69 (1H, dd, J=7.7, 2.1 Hz, Ar-H), 8.03 (1H, d, J=1.8 Hz, Ar-H), 7.70 (1H,
m, Ar-H), 7.56 (1H, d, J=8.6 Hz, Ar-H), 7.39 (1H, dd, J=8.6, 1.8 Hz, Ar-H); MS (EI) m/z (%): 272 (M+2,
+
3
3), 270 (M , 100), 235 (13). HRMS (EI) calcd. for C14
H
7
ClN
2
O
2
, 270.0196; found 270.0188.
9
-Nitro-4-azachromeno[2,3-b]indol-11(6H)-one (4c)
Compound (4c) was prepared in the same way as method B from 5-nitroindolin-2-one (178 mg, 1 mmol) ,
Ca(OH) (148 mg, 2 mmol), and 2-chloronicotinoyl chloride (175 mg, 1 mmol) to give red solid. Yield:
2
1
1
08 mg (38.4%); mp＞300°C; H NMR (300MHz, DMSO-d
6
): δ 13.80 (1H, s, NH), 8.85 (1H, d, J=2.1
Hz, Ar-H), 8.78 (1H, dd, J=4.9, 1.7 Hz, Ar-H), 8.71 (1H, dd, J=7.5, 1.7 Hz, Ar-H), 8.24 (1H, dd, J=8.8,
+
2
.1 Hz, Ar-H), 7.72 (2H, m, Ar-H); MS (EI) m/z (%): 281 (M , 15), 235 (7). HRMS (EI) calcd. for
C
14
H
7
N
3
O
4
, 281.0436; found 281.0432.
6
-Methyl-4-azachromeno[2,3-b]indol-11(6H)-one (5a)

256
HETEROCYCLES, Vol. 80, No. 1, 2010
To a solution of 4-azachromeno[2,3-b]indol-11(6H)-one(118 mg, 0.5 mmol) in 10 mL of DMF was added
CO (276 mg, 2 mmol). After 30 min, CH I (71 mg, 31 μL, 0.5 mmol) was added. The reaction mixture
K
2
3
3
was stirred at rt for 6 h and poured into 100 mL of water . The resulting white solid was filtered, and dried.
1
Yield: 56 mg (44.8%); mp 244-247°C; H NMR (300MHz, DMSO-d
6
): δ 8.75 (1H, dd, J=4.3, 1.2 Hz,
Ar-H), 8.68 (1H, dd, J=7.7, 1.2 Hz, Ar-H), 8.11 (1H, d, J=7.0 Hz, Ar-H), 7.69 (2H, m, Ar-H), 7.38 (2H,
+
m, Ar-H), 3.92 (3H, s, NCH
, 250.0742; found 250.0750.
-Ethyl-4-azachromeno[2,3-b]indol-11(6H)-one (5b)
3
); MS (EI) m/z (%): 250 (M , 100), 221 (12). HRMS (EI) calcd. for
15 10 2 2
C H N O
6
The compound was synthesized from 4-azachromeno[2,3-b]indol-11(6H)-one (118 mg, 0.5 mmol) and
EtI (78 mg, 41 μL, 0.5 mmol) according to the procedure for compound (5a). Yield: 47 mg (35.6%); mp
1
1
2
80-182°C; H NMR (300MHz, DMSO-d
6
): δ 8.75 (1H, dd, J=4.4, 2.0 Hz, Ar-H), 8.68 (1H, dd, J=7.7,
.0 Hz, Ar-H), 8.13 (1H, d, J=7.1 Hz, Ar-H), 7.71 (2H, m, Ar-H), 7.38 (2H, m, Ar-H), 4.47 (2H, q, J=7.0
+
Hz, CH
2
), 1.46 (3H, t, J=7.0 Hz, CH
, 264.0899; found 264.0894.
-(2-Aminoethyl)- 4-azachromeno[2,3-b]indol-11(6H)-one (5c)
To a suspension of 4-azachromeno[2,3-b]indol-11(6H)-one (118 mg, 0.5 mmol) in 10 mL of acetone was
added K CO (207 mg, 1.5 mmol). After 30 min, 2-bromoethanamine hydrobromide (103 mg, 0.5 mmol)
was added. The reaction mixture was heated under reflux for 3 days and filtered. The filtrate was purified
3
); MS (EI) m/z (%): 264 (M , 100), 249 (80). HRMS (EI) calcd. for
16 12 2 2
C H N O
6
2
3
by column chromatography on silica gel (CH
2
Cl
2
/MeOH, 10/1, v/v) to give compound (5c). Yield: 16 mg
): δ 8.75 (1H, dd, J=4.8, 2.0 Hz, Ar-H), 8.71 (1H,
1
(
11.5%); mp 179-183°C; H NMR (300MHz, DMSO-d
6
dd, J=7.6, 2.0 Hz, Ar-H), 8.14 (1H, dd, J=7.2, 1.8 Hz, Ar-H), 7.77 (1H, dd, J=7.1, 1.1 Hz, Ar-H), 7.70
2 2
(1H, m, Ar-H), 7.39 (2H, m, Ar-H), 4.40 (2H, t, J=6.1 Hz, CH ), 3.04 (2H, t, J=6.1 Hz, CH ); MS (EI)
+
m/z (%): 279 (M , 36), 250 (100), 249 (85). HRMS (EI) calcd. for C H N O , 279.1008; found
1
6
13
3
2
2
6
2
6
79.1002.
-[2-(Dimethylamino)ethyl]- 4-azachromeno[2,3-b]indol-11(6H)-one (5d)
1
6
-Chloro-N, N-dimethylethanamine hydrochloride was prepared according to known procedures. Yield:
1
50 mg (40.0%); mp 228-229°C (lit., mp 201-203°C); H NMR (300MHz, CD
3
OD): δ 3.99 (2H, t, J=5.7
Hz, CH
Compound (5d) was synthesized from 4-azachromeno[2,3-b]indol-11(6H)-one (236 mg, 1mmol) and
-chloro-N, N-dimethylethanamine hydrochloride (143 mg, 1 mmol) according to the procedure for
2 2 3 2
Cl), 3.58 (2H, t, J=5.7 Hz, NCH ), 2.97 (6H, s, N(CH ) ).
2
compound (5a). The reaction was not completed after 24 h. After workup, the precipitated solid was 55
mg of the mixture of the starting material and the product. The mixture was not soluble , so it was
difficult to separate. The filtrate stayed overnight to gain 18 mg of pure product. Yield: 18 mg (5.8%); mp
1
1
30-133°C; H NMR (300MHz, DMSO-d
6
): δ 8.76 (1H, dd, J=4.4, 2.0 Hz, Ar-H), 8.70 (1H, dd, J=7.8,

HETEROCYCLES, Vol. 80, No. 1, 2010
257
2.0 Hz, Ar-H), 8.13 (1H, dd, J=7.4, 1.8 Hz, Ar-H), 7.71 (2H, m, Ar-H), 7.39 (2H, m, Ar-H), 4.51 (2H, t,
+
J=6.3 Hz, CH
2
), 2.74 (2H, t, J=6.3 Hz, CH
40). HRMS (EI) calcd. for C18 , 307.1321; found 307.1321.
-[2-(Piperidin-1-yl)ethyl]- 4-azachromeno[2,3-b]indol-11(6H)-one (5e)
2
), 2.22 (6H, s, NMe
2
); MS (EI) m/z (%): 307 (M , 100), 249
(
17 3 2
H N O
6
To a solution of 4-azachromeno[2,3-b]indol-11(6H)-one(118 mg, 0.5 mmol) in 10 mL of DMF was added
CO (207 mg, 1.5 mmol). After 30 min, 1-(2-chloroethyl)piperidine hydrochloride (92 mg, 0.5 mmol)
and NaI (7.5 mg, 0.05 mmol) was added. The reaction mixture was stirred at rt for 7 h and poured into
00 mL of water . The resulting yellow solid was filtered, and dried. The crude product was purified by
K
2
3
1
column chromatography on silica gel (CH
2
Cl
2
/MeOH, 25/1, v/v) to give compound (5e). Yield: 14 mg
1
(
8%); mp 167-169°C; H NMR (300MHz, DMSO-d
6
): δ 8.75 (1H, dd, J=4.5, 2.0 Hz, Ar-H), 8.70 (1H, dd,
J=7.7, 2.0 Hz, Ar-H), 8.13 (1H, d, J=6.6 Hz, Ar-H), 7.73 (1H, d, J=7.9 Hz, Ar-H), 7.70 (1H, m, Ar-H),
2 2 2
7.38 (2H, m, Ar-H), 4.52 (2H, t, J=6.2 Hz, CH ), 2.70 (2H, t, J=6.2 Hz, CH ), 2.41 (4H, s, CH ), 1.29 (6H,
+
m, CH ); MS (EI) m/z (%): 347 (M , 4), 249 (5), 98 (100). HRMS (EI) calcd. for C H N O , 347.1634;
2
21 21
3
2
found 347.1633.
9
-Chloro-6-[2-(piperidin-1-yl)ethyl]- 4-azachromeno[2,3-b]indol-11(6H)-one (5f)
Compound (5f) was synthesized from 9-chloro-4-azachromeno[2,3-b]indol-11(6H)-one (135 mg, 0.5
mmol) and 1-(2-chloroethyl)piperidine hydrochloride (102 mg, 0.55 mmol) according to the procedure
2 3
for compound (5e). The reaction mixture was stirred for 48 h at rt, filtered to remove K CO and poured
1
into 50 mL of water to gain gray solid. Yield: 60 mg (31.5%); mp 176-179°C; H NMR (300MHz,
CDCl
Ar-H), 7.55 (1H, m, Ar-H), 7.35 (2H, m, Ar-H), 4.47 (2H, t, J=6.2 Hz, CH
.49 (4H, s, CH ), 1.47 (4H, s, CH ), 1.38 (2H, s, CH
HRMS (EI) calcd. for C H ClN O , 381.1244; found 381.1229.
3
): δ 8.84 (1H, dd, J=7.7, 2.0 Hz, Ar-H), 8.67 (1H, dd, J=4.4, 2.0 Hz, Ar-H), 8.33 (1H, t, J=1.2 Hz,
2
2
), 2.78 (2H, t, J=6.2 Hz, CH ),
+
2
2
2
2
); MS (EI) m/z (%): 381 (M , 8), 283 (22), 98 (100).
21
20
3
2
ACKNOWLEDGEMENTS
This work was financially supported by the Innovation Program of the Chinese Academy of Sciences
Grant No. KSCX2-YW-R-25).
(
REFERENCES AND NOTES
1.
2.
3.
4.
5.
Q. Zhang, C. Shi, H. R. Zhang, and K. K. Wang, J. Org. Chem., 2000, 65, 7977.
X. Lu, J. L. Petersen, and K. K. Wang, J. Org. Chem., 2002, 67, 5412.
Y. Miki, Y. Aoki, Y. Tsuzaki, M. Umemoto, and H. Hibino, Heterocycles, 2005, 65, 2693.
M. Dračínský, J. Sejbal, B. Rygerová, and M. Stiborová, Tetrahedron Lett., 2007, 48, 6893.
M. Monnot, O. Mauffret, V. Simon, E. Lescot, B. Psaume, J. M. Saucier, M. Charra, J. Belehradek,

258
HETEROCYCLES, Vol. 80, No. 1, 2010
Jr., and S. Fermandjian, J. Biol. Chem., 1991, 266, 1820.
6
.
F. Searle, S. Gac-Breton, R. Keane, S. Dimitrijevic, S. Brocchini, E. A. Sausville, and R. Duncan,
Bioconjugate Chem., 2001, 12, 711.
7
8
.
.
A. Langendoen, G. J. Koomen, and U. K. Pandit, Heterocycles, 1987, 26, 69.
N. Desbois, J. M. Chezal, F. Fauvelle, J. C. Debouzy, C. Lartigue, A. Gueiffier, Y. Blache, E.
Moreau, J. C. Madelmont, O. Chavignon, and J. C. Teulade, Heterocycles, 2005, 65, 1121.
R. A. Jones, J. Pastor, J. Siro, and T. N. Voro, Tetrahedron, 1997, 53, 479.
9
1
1
1
1
1
1
1
.
0. M. L. Bennasar, T. Roca, and F. Ferrando, J. Org. Chem., 2005, 70, 9077.
1. G. Eller, V. Wimmer, A. Haring, and W. Holzer, Synthesis, 2006, 4219.
2. L. M. Werbel, M. Angelo, D. W. Fry, and D. F. Worth, J. Med. Chem., 1986, 29, 1321.
3. V. Bonnet, F. Mongin, F. Trécourt, G. Quéguiner, and P. Knochel, Tetrahedron, 2002, 58, 4429.
4. W. C. Sumpter, M. Miller, and M. E. Magan, J. Am. Chem. Soc., 1945, 67, 499.
5. W. G. Rajeswaran and L. A. Cohen, Tetrahedron, 1998, 54, 11375.
6. R. Fornasier, P. Scrimin, P. Tecilla, and U. Tonellato, J. Am. Chem. Soc., 1989, 111, 224.