SYNTHESIS OF AMPHIPHILIC meso-TETRASUBSTITUTED PORPHYRIN-L-AMINO ACID
5
with the aid of an ice/salt bath; DIPEA (25 mmL,
the mixture was allowed to stir at 0°C for 3 h, then at
room temperature for 12 h. The residue was purified by
preparative TLC silica gel plate (CHCl3/MeOH, 7:0.5,
v/v) to afford 16 as a purple solid (25 mg, 0.018 mmol,
21%). Mp = 120–122°C; Rf = 0.57 (CH2Cl2/MeOH, 7:
0.5, v/v); 1H NMR (500 MHz, CDCl3): dH = 8.63 (bs, 8H,
b-H), 8.33 (bs, 1H, Ar–H), 8.13 (m, 6H, Ar–H), 7.96 (t,
J = 5 Hz, 1H, Ar–H), 7.87 (q, J = 10 Hz, 4H, Ar–H), 7.48
(m, 4H, Ar–H), 6.91 (m, 2H, Ar–H), 6.44 (m, 2H, Ar–H),
5.36 (m, 1H, NHCHCO), 4.87 (s, 2H, OCH2CO), 4.30 (bs,
6H, OCH2), 3.72 (bs, 3H, OCH3), 3.01 (m, 1H, CH-phe),
2.80 (m, 1H, CH-phe), 1.99 (m, 6H, CH2), 1.60–1.43 (bs,
18H, CH2), 0.94 (br s, 9H, CH3), -3.03 ppm (s, 2H, NH).
13C NMR (125 MHz, CDCl3): dc = 171.6, 168.1, 157.8,
157.8, 155.8, 143.5, 141.3, 130.7, 127.7, 121.3, 120.6,
115.4, 68.9, 68.2, 52.4, 37.4, 31.9, 29.8, 26.0, 23.1,
14.3 ppm. HRMS (MALDI) m/z calcd for [C74H79N5O8]
(M + H)+: 1165.5929, found 1165.5914; UV-vis (MeOH):
lmax (log e) = 419 (5.47), 514 (4.09), 549 (3.65), 589
(3.57), 644 nm (3.32).
0.14 mmol) was added and the mixture was allowed to
stir at 0°C for 3 h, then at room temperature for 12 h. The
residue was purified by preparative TLC silica gel plate
(CHCl3/MeOH, 3:0.2, v/v) to afford 14 as a purple solid
(73 mg, 0.059 mmol, 66%). Mp = 210–212°C; Rf = 0.5
(CH2Cl2/MeOH, 5 : 1, v/v); 1H NMR (500 MHz, CDCl3):
dH = 8.83 (bs, 8H, b-H), 7.75 (bs, 8H, Ar–H), 7.58 (m,
6H, Ar–H), 7.34 (d, J = 5 Hz, 2H, Ar–H), 4.98 (s, 2H,
OCH2CO), 4.82 (s, 6H, OCH2), 4.55 (dd, J = 5 Hz, J =
10 Hz, 1H, CH, L-pro-H), 3.59 (d, J = 5 Hz, 3H, OCH3),
3.40 (d, J = 5 Hz, 2H, CH2, L-pro-H), 1.95 (m, 2H, CH2,
L-pro-H), 1.81 (m, 2H, CH2, L-pro-H)), 1.83 (m, 4H,
CH2), 1.47 (m, 6H, CH2), 1.31 (m, 14H, CH2), 0.92 (m,
9H, CH3), -3.02 ppm (s, 2H, NH). 13C NMR (125 MHz,
CDCl3): dc = 172.4, 172.3, 166.8, 157.5, 156.4, 143.5,
143.3, 127.9, 127.6, 127.5, 127.4, 121.1, 120.8, 114.1,
108.5, 68.2, 67.5, 59.1, 52.2, 47.4, 46.3, 31.6, 29.4, 29.3,
25.7, 22.6, 14.1 ppm. HRMS (MALDI) m/z calcd for
[C70H77N5O7] (M + H)+: 1099.5823, found 1099.5831;
UV-vis (CH2Cl2): lmax (log e) = 419 (5.8), 514 (4.5), 549
(4.2), 589 (4.1), 645 nm (4.0).
Synthesis of porphyrin derivatives containing
heterocycles
[5,10,15-Tris(3-hydroxyphenyl)-20-(L-tyrosine methyl
ester-N-acetyloxy phenyl)]porphyrin (15). Following
general procedure A, compound 4 (70 mg, 0.087 mmol),
L-tyrosine methyl ester (20 mg, 0.087 mmol) and HBTU
(50 mg, 0.13 mmol) were dissolved in dry THF (9 mL). The
reaction mixture was kept at -5–0°C with the aid of an ice/
salt bath. Then DIPEA (23 µmL, 0.13 mmol) was added
and the mixture was allowed to stir at 0°C for 3 h, then
at room temperature for 12 h. The residue was purified
by column chromatography (CHCl3/MeOH, 10:1, v/v) to
afford 15 as a purple solid (47 mg, 0.035 mmol, 60%).
Mp = 190–192°C; Rf = 0.42 (CH2Cl2/MeOH, 10: 1, v/v);
1H NMR (500 MHz, (CD3)2SO): dH = 9.87 (s, 3H, Ar–
OH), 9.15 (s, 1H, Ar–OH), 8.84 (s, 8H, b-H), 7.77 (bs,
2H, Ar–H), 7.67 (t, J = 10 Hz, 1H, Ar–H), 7.55 (bs, Hz,
9H,Ar–H), 7.29 (d, J = 5 Hz, 1H,Ar–H), 7.20 (d, J = 5 Hz,
3H, Ar–H), 6.93 (m, 2H, Ar–H), 6.55 (m, 2H, Ar–H),
4.86 (s, 2H, OCH2CO), 4.47 (q, 1H, J = 5 Hz, J = 10 Hz,
NHCHCO), 3.41 (d, J = 5 Hz, 3H, OCH3), 2.88 (m, 1H,
CH-phe), 2.84 (m, 1H, CH-phe), -3.03 ppm (s, 2H, NH).
13C NMR (125 MHz, (CD3)2SO): dc = 172.4, 171.8,
169.4, 167.9, 156.0, 155.8, 142.5, 142.4, 130.1, 129.9,
127.9, 127.0, 125.8, 121.9, 120.0, 119.9, 119.4, 115.1,
66.8, 53.7, 51.8, 36.0, 35.8 ppm. HRMS (MALDI) m/z
calcd for [C56H43N5O8] (M)+: 913.3112, found 913.3099;
UV-vis (MeOH): lmax (log e) = 414 (5.6), 512 (4.3), 546
(4.0), 587 (3.9), 644 nm (3.7).
[5,10,15-Tris(3-hydroxyphenyl)-20-(3-(2-indolyl-3-
yl-acetate))phenyl]porphyrin (24). In a predried 25 mL
round bottomed flask charged with a magnetic stirrer and
flushedwithargon, 5,10,15,20-tetrakis(3-hydroxyphenyl)
porphyrin, m-THPP 1 (300 mg, 0.44 mmol), indole
3-acetic acid 18 (800 mg, 4.40 mmol, 10 eq.), EDCI
(900 mg, 4.40 mmol, 10 eq.), HOBt (600 mg, 4.40
mmol, 10 eq.) and K2CO3 (600 mg, 4.40 mmol, 10
eq.) were dissolved in dry DMF (10 mL). The reaction
mixture was allowed to stir at room temperature under
argon. The reaction progress was monitored by TLC and
the maximum yield (19%) of the desired compound 24
was obtained after 40 h. The reaction was terminated by
adding EtOAc (50 mL) and the mixture was transferred
into a separating funnel then washed with water (3 ×
50 mL), brine (3 × 50 mL), and water (3 × 50 mL). The
organic layer was dried over anhydrous MgSO4, filtered,
and the solvent was removed under reduced pressure.
The residue was purified by column chromatography
with a gradient solvent system (CH2Cl2/petroleum ether
60–80°C/MeOH, 600/200/0 to 600/200/15, v/v/v) to
afford 24 (fraction 4 from the column) as a purple solid
(70 mg, 0.084 mmol, 19%). Mp = 192–194°C; Rf =
0.47 (CH2Cl2/petroleum ether 60–80°C/MeOH, 3:1:0.2,
1
v/v/v); H NMR (500 MHz, (CD3)2SO): dH = 10.96 (s,
[5,10,15-Tris(3-hexyloxyphenyl)-20-(L-tyrosine
methyl ester-N-acetyloxy) phenyl]porphyrin (16). Fol-
lowing general procedure A, compound 5 (100 mg,
0.099 mmol), L-tyrosine methyl ester (23 mg,
0.099 mmol) and HBTU (57 mg, 0.15 mmol) were
dissolved in dry THF (15 mL). The reaction mixture
was kept at -5–0°C with the aid of an ice/salt bath.
Then DIPEA (26 mmL, 0.15 mmol) was added and
1H, NH-indole), 9.87 (s, 3H, Ar–OH), 8.85 (bs, 8H,
b-H), 8.09 (d, J = 5 Hz, 1H, Ar–H), 7.96 (bs, 1H, Ar–H),
7.82 (t, J = 10 Hz, J = 15 Hz, 1H, CH-indole), 7.58 (m,
11H, Ar–H), 7.35 (bs, 1H, CH-indole), 7.31 (d, J = 5 Hz,
1H, CH-indole), 7.20 (d, J = 10 Hz, 3H, Ar–H), 7.01 (t,
J = 10 Hz, J = 15 Hz, 1H, CH-indole), 6.91 (t, J = 5 Hz,
J = 15 Hz, 1H, CH-indole), 4.10 (s, 2H, CH2), -3.04 ppm
(s, 2H, NH). 13C NMR (125 MHz, (CD3)2SO): dc = 171.3,
Copyright © 2018 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2018; 22: 5–13