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L. Uzelac et al. / European Journal of Medicinal Chemistry 137 (2017) 558e574
5
.1.1. 3-Hydroxmethyl-2-hydroxyanthracene (2)
Aldehyde 6 (175 mg, 0.71 mmol) was suspended in CH
1:1, 20 mL) and NaBH was added under inert atmosphere (N
5.1.4. Preparative photochemical methanolysis
3
OH-THF
).
(
4
2
5.1.5. Irradiation of 3-hydroxymethyl-2-hydroxyanthracene (2)
Compound 2 (15 mg, 0.067 mmol) was dissolved in methanol
(80 mL) in a quartz vessel, and water (20 mL) was added. The
resulting solution was purged with a stream of Ar (20 min), and
irradiated in a Rayonet reactor using 12 lamps at 350 nm for 15 min.
Prior to and during the irradiation, the solution was continuously
purged with a stream of Ar and cooled using a coldfinger condenser.
The reaction was monitored by HPLC and the irradiation was
stopped when ~80% conversion to the photoproduct was achieved.
The solvent was removed on a rotary evaporator and the crude
The reaction mixture was stirred overnight at rt, whereupon the
color changed from orange to pale yellow and a precipitate was
formed. Water (20 mL) was added dropwise, followed by the
addition of 1 M HCl until pH~3 was achieved. The stirring was
continued for 15 min, and the product was filtered off. The product
was washed with a large amount of water until neutral pH of the
filtrate was achieved, then dried in an evacuated dessicator over
KOH. Pure product 2 (155 mg, 98%) was obtained in the form of
yellowish powder.
2 2
product was purified on short column of silica gel using CH Cl as
an eluent to give product 8 (13 mg, 80%) of in the form of pale
yellow film.
3
2
8
2
-Hydroxmethyl-2-hydroxyanthracene (2): 155 mg (98%); m. p.
ꢃ
1
28e230 C; H NMR (300 MHz, DMSO-d
6
) d/ppm: 10.0 (br. s, 1H),
.42 (s, 1H), 8.24 (s, 1H), 8.00e7.93 (m þ s, 2Hþ1H), 7.46e7.32 (m,
13
3-Methoxymethyl-2-hydoxyanthracene (8) [26]: 13 mg (80%); m. p.
H), 7.21 (s, 1H), 5.70 (br. s, 1H), 4.68 (s, 2H); C NMR (150 MHz,
/ppm: 153.2 (s), 133.7 (s), 132.0 (s), 131.3 (s), 129.4 (s),
28.0 (d), 127.4 (s), 127.3 (d), 125.4 (d), 125.1 (d), 125.0 (d), 123.9 (d),
ꢃ
1
1
89e192 C; H NMR (300 MHz, CDCl
3
) d/ppm: 8.29 (s, 1H), 8.22 (s,
6
DMSO-d ) d
1
H), 7.95e7.88 (m, 2H), 7.73 (s, 1H), 7.45e7.37 (m, 2H), 7.36 (s, 1H),
1
13
ꢁ
1
4.84 (s, 2H), 3.50 (s, 3H); C NMR (75 MHz, CDCl
32.8 (s), 132.2 (s), 130.3 (s), 128.2 (d), 128.0 (d), 127.7 (d), 126.2 (s),
126.1 (d),125.5 (d),124.4 (d),123.8 (d),109.3 (d), 74.2 (t), 58.2 (q); IR
3
) d/ppm: 153.5 (s),
1
22.3 (d), 105.9 (d), 58.8 (d); IR (KBr) v~ /cm : 3448 (s), 3182 (m),
1
2
7
930 (w), 1699 (s), 1447 (m), 1244 (w), 1213 (m), 1005 (m), 893 (m),
37 (s), 474 (m); HRMS-MALDI calcd. for C15H O (-e ) 224.0832,
12 2
-
ꢁ1
(
(
KBr) ~v /cm : 3228 (m), 2928 (m),1637 (s),1445 (m),1213 (m),1076
m), 887 (s), 737 (m), 473 (m).
found 224.0830.
5
.1.2. 3-Methoxyanthracene-2-carbaldehyde (7)
Aldehyde 6 (100 mg, 0.45 mmol), K CO (200 mg, 1.45 mmol)
and MeI (100 L, 1.61 mmol) were dissolved in dry THF (10 mL) and
5
.1.6. 3-Azidomethyl-2-hydroxyanthacene (9)
Compound 2 (15 mg, 0.067 mmol) was dissolved in acetonitrile
2
3
m
3
(70 mL) and the solution of NaN (1 g, 15 mmol) in water (30 mL)
the resulting suspension was heated on reflux overnight. The sol-
vent was removed on a rotary evaporator and the solid residue was
was added. Photolysis was carried out in a Rayonet reactor using 11
lamps at 350 nm for 30 min. Prior to and during the irradiation, the
solution was continuously purged with a stream of Ar and cooled
using a coldfinger condenser. After the irradiation, the solution was
extracted with CH
was removed on a rotary evaporator. The crude product was puri-
fied on column of silica gel using CH Cl as an eluent. Product 7
64 mg, 60%) was obtained in the form of yellow crystalline solid.
2
Cl
2
(3 ꢀ 15 mL). After the filtration, the solvent
2
2
poured on water (150 mL) and extracted with Et
combined extracts were washed with water (2 ꢀ 100 mL), dried
over anhydrous MgSO , filtered, and the solvent was removed on a
rotary evaporator. The crude product was purified on column of
Cl as an eluent to regenerate
O (3 ꢀ 20 mL). The
2
(
4
-Methoxyanthracene-2-carbaldehyde (7): 64 mg (60%); 1H NMR
3
silica gel (10 ꢀ 1 cm) using CH
2
2
(
300 MHz, CDCl
3
) d/ppm: 10.6 (s, 1H), 8.53 (s, 1H), 8.47 (s, 1H), 8.23
starting compound (5 mg, 21%) and isolate product 9 (8 mg, 30%) in
the form of yellowish film.
(
s, 1H), 7.99e7.88 (m, 2H), 7.53e7.38 (m, 2H), 7.23 (s, 1H), 4.04 (s,
13
3
3
H); C NMR (75 MHz, CDCl ) d/ppm: 190.0 (d), 156.1 (s), 134.0 (s),
1
33.7 (s), 132.6 (d), 130.7 (s), 129.6 (d), 128.4 (d), 127.4 (d), 126.9 (d),
ꢃ
3
-Azidomethyl-2-hydroxyanthacene (9): 8 mg (30%); m. p. 201
C
126.6 (s), 124.9 (d), 124.0 (d), 104.3 (d), 55.4 (q).
1
(dec.); H NMR (300 MHz, acetone-d
6
) d/ppm: 9.30 (br. s, 1H), 8.47
(
3
1
1
s, 1H), 8.26 (s, 1H), 8.04 (s, 1H), 8.03e7.92 (m, 2H), 7.50e7.35 (m,
5
.1.3. 3-Hydroxymethyl-2-methoxyanthracene (5)
In a round bottom flask (25 mL) aldehyde 7 (50 mg, 0.21 mmol)
13
6
H), 4.64 (s, 2H); C NMR (150 MHz, acetone-d ) d/ppm: 155.0,
41.27, 141.25, 135.52, 135.46, 131.6, 130.7, 129.7, 128.6, 128.4, 127.6,
was suspended in EtOH (10 mL). Under inert atmosphere (N
NaBH (20 mg, 0.53 mmol) was added. The yellow suspension
immediately become clear and the color changed to pale yellow.
The resulting mixture was stirred 1 h at rt. The solvent was
removed on a rotary evaporator and the resulting solid residue was
2
)
ꢁ1
26.0, 125.2, 124.8, 110.1; IR (KBr) v~ /cm : 3440, 2958, 2925, 2854,
4
-
1
639, 1462, 1379, 892; HRMS-MALDI calcd. for C15
H
11
N
3
O (-e )
2
5
2
49.0900, found 249.0892.
.1.7. Irradiation in the presence of N,C-protected cysteine 13
2 2
suspended in water (15 mL). The product was extracted with CH Cl
In a UVevis cuvette (1 ꢀ 1 cm) was placed solution of compound
(
5 ꢀ 15 mL), the combined extracts were dried over anhydrous
ꢁ4
ꢁ2
(5 ꢀ 10 M, 3 mL) containing protected cysteine 13 (5 ꢀ 10
M
4
MgSO , filtered and the solvent was removed on a rotary evapo-
3 2 2
in CH CN-H O 9:1). The solution was purged with N (30 min) and
then irradiated in a Luzchem reactor with 8 lamps (350 nm,
8
has proved that photoproduct is identical to the synthetically pre-
pared sample.
rator. Product 5 (42 mg, 84%) was obtained in the form of yellowish
solid.
ꢀ 8 W) for 20 min. HPLC analysis of the photoreaction mixture
3-Hydroxymethyl-2-methoxyanthracene (5): 42 mg (84%); m. p.
ꢃ
1
150e152 C; H NMR (300 MHz, CDCl
3
)
d
/ppm: 8.25 (s, 1H), 7.95 (s,
1
1
H), 7.94 (t, 2H, J ¼ 9.4 Hz), 7.86 (s, 1H), 7.46e7.38 (m, 2H), 7.19 (s,
5.1.8. Irradiation in the presence of lysine
13
H), 4.85 (s, 2H), 3.99 (s, 3H); C NMR (150 MHz, CDCl
3
)
d
/ppm:
In a UVevis cuvvete (1 ꢀ 1 cm) was placed a solution of com-
ꢁ
4
155.7 (s), 132.2 (s), 132.0 (s), 131.6 (s), 130.5 (s), 128.1 (d), 127.9 (s),
pound 2 (1 ꢀ 10 M, 3 mL) containing of lysine (0.2 M in CH
3
CN-
127.5 (d), 126.1 (d), 125.4 (d), 124.4 (d), 123.8 (d), 103.5 (d), 62.5 (t),
2 2
H O 4:1). The solution was purged with N (30 min) and then
ꢁ
1
5
5.3 (q); IR (KBr) v~ /cm : 3281 (m), 2862 (w), 1637 (m), 1466 (m),
irradiated in a Luzchem reactor with 8 lamps (350 nm) for 40 min.
The solvent was removed on a rotary evaporator and excess of
lysine was removed by washing of the solid residue with water.
1273 (w), 1217 (s), 1009 (m), 905 (m), 739 (m), 473 (m); HRMS-
-
14 2
MALDI calcd. for C16H O (-e ) 238.0990, found 238.0992.