RGD-Porphyrin Conjugates
FULL PAPER
chromatography performed with CHCl
3
and increasing amounts of
Porphyrin 4a (100 mg, 0.06 mmol, 1 equiv.), compound 1 (66 mg,
ethanol (0 to 10%) allowed purification of porphyrins 7a and 7b.
0.3 mmol, 5 equiv.) and K
forded pure product 6a (92 mg, 85%) R
2
CO
3
(165 mg, 1.2 mmol, 20 equiv.) af-
ϭ 0.43 (CHCl /EtOH,
2 2
Cl ): λ (ε, ϫ 10 ) ϭ 420 (390.0), 518 (13.8),
f
3
Triglucosyl porphyrin 6a or 6b was dissolved in dichloromethane
Ϫ3
9
5
5:5). UV/visible (CH
53 (8.7), 592 (4.9), 650 nm (4.5). H NMR (400 MHz, CDCl
(8 mL), and trifluoroacetic acid (2 mL) was then added. The mix-
1
3
, 25
tert-butyl), 2.10 (s,
ture was stirred at room temperature for 2 h. At the end of the
reaction, dichloromethane (30 mL) was added, followed by satu-
rated aqueous NaHCO solution until pH ϭ 7. The organic layer
3
was washed with water and dried over magnesium sulfate. Porphy-
rins 8a and 8b were obtained pure by column chromatography with
°
9
C): δ ϭ Ϫ2.79 (s, 2 H, NH), 1.53 (s, 9 H, CH
3
H, CH
3
), 2.11 (s, 9 H, CH
3
3
), 2.12 (s, 9 H, CH ), 2.21 (s, 9 H,
CH
3
), 2.27 (q, JH,H ϭ 6.68 Hz, 2 H, H
.32 Hz, 2 H, H ϪCH ϪCϭO), 4.06 (ddd, JH,H ϭ 9.94, 5.38,
.24 Hz, 3 H, 5Ј-H ose), 4.30 (m, 2 H, H ϪOϪCH Ϫ), 4.30 (m,
H, 6Јb-H ose), 4.42(dd, JH,H ϭ 12.32, 5.44 Hz, 3 H, 6Јa-H ose),
β 2
ϪCH Ϫ), 2.61 (t, JH,H ϭ
7
2
3
γ
2
α
2
3
CHCl and increasing amounts of ethanol (0 to 10%).
5
-[4-(3-Ethoxycarbonylpropyloxy)phenyl]-10,15,20-tris(4-methyl- 5.30 (m, 3 H, 4Ј-H ose), 5.46 (m, 9 H, 3Ј,2Ј,1Ј-H ose), 7.28 (d,
phenyl)porphyrin (5a): Porphyrin 3a (150 mg, 0.22 mmol, 1 equiv.),
JH,H ϭ 8.56 Hz, 2 H, 2,6-H Ar), 7.38 (d, JH,H ϭ 8.4 Hz, 6 H, 3,5-
ethyl 4-bromobutyrate (159 mL, 1.1 mmol, 5 equiv.) and K CO
H Ar-ose), 8.10 (d, JH,H ϭ 8.6 Hz, 2 H, 3,5-H Ar), 8.13 (d, JH,H
615 mg, 4.4 mmol, 20 equiv.) afforded pure product 5a, 167 mg,
8.0 Hz, 6 H, 2,6-H Ar-ose), 8.83 (d, JH,H ϭ 4.76 Hz, 2 H, H pyr),
2
3
ϭ
(
(
4
(
J
β
Ϫ3
90%). R
20 (354.0), 516 (14.3), 552 (7.2), 592 (4.7), 648 nm (4.2). H NMR
400 MHz, CDCl , 25 °C): δ ϭ Ϫ2.71 (br. s, 2 H, NH pyr),1.36 (t,
H,H ϭ 7.2 Hz, 3 H, CH ethyl), 2.31 (m, 2 H, H ϪCH Ϫ), 2.66 119.1, 119.2, 120.3, 131.0, 134.4, 135.5, 135.6, 137.2, 146.5, 156.6,
m, 2 H, H ϪCH ϪCϭO), 4.25 (q, JH,H ϭ 7.1 Hz, 2 H, CH
158.9, 169.4, 170.3, 170.6, 170.7 ppm. SM (MALDI): m/z ϭ
ethyl), 4.30 (t, JH,H ϭ 6.0 Hz, 2 H, H ϪOϪCH Ϫ), 7.26 (d, 1528.31 [M ϩ H] .
H,H ϭ 8.6 Hz, 2 H, 3,5-H Ar), 7.56 (d, JH,H ϭ 7.8 Hz, 6 H, 3,5-
H tolyl), 8.11 (d, JH,H ϭ 7.7 Hz, 2 H, 2,6-H Ar), 8.12 (d, JH,H
.7 Hz, 6 H, 2,6-H tolyl), 8.88 (s, 8 H, H pyr) ppm. SM (MALDI):
f
ϭ 0.56 (CHCl
3
). UV/visible (CH
2
Cl
2
): λ (ε, ϫ 10 ) ϭ 8.84 (s, 4 H, H pyr) 8.87 (d, J
H,H β
ϭ 4.76 Hz, 2 H, H pyr) ppm.
β
1
13
C NMR (CDCl , 25 °C): δ ϭ 20.65, 20.69, 20.78, 20.82, 25.0,
3
3
28.2, 32.2, 53.4, 62.1, 67.2, 68.4, 71.3, 72.3, 72.8, 99.2, 112.8, 115.1,
3
β
2
(
β
2
2
ϩ
α
2
J
ϭ
10,15,20-Tris[4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β-D-glucopyranosyloxy)-
7
β
phenyl]-5-[4-(3-carboxypropyloxy)phenyl]porphyrin (8a): Hydrolysis
of porphyrin ester 6a (carried out on 120 mg) gave porphyrins 8a
ϩ
m/z ϭ 787.89 [M ϩ H] .
-[4-(3-Carboxypropyloxy)phenyl]-10,15,20-tris(4-methylphenyl)-
porphyrin (7a): The saponification of 5a (carried out on 100 mg)
gave porphyrin 7a in 98% yield. R ϭ 0.49 (CHCl /EtOH, 95:5).
): λ (ε, ϫ 10 ) ϭ 420 (355.7), 517 (13.4), 553
Ϫ3
(
(
(
2 2
110 mg, 95% yield). UV/visible (CH Cl ): λ (ε, ϫ 10 ) ϭ 421
5
1
432.0), 517 (13.1), 553 (11.0), 592 (5.2), 648 nm (3.8). H NMR
400 MHz, CDCl , 25 °C): δ ϭ Ϫ2.79 (s, 2 H, NH), 2.08 (s, 9 H,
), 2.09 (s, 9 H, CH ), 2.10 (s, 9 H, CH ), 2.19 (s, 9 H, CH ),
.34 (q, JH,H ϭ 5.36 Hz, 2 H, H ϪCH Ϫ), 2.78 (t, JH,H ϭ 7.12 Hz,
H, H ϪCH ϪCϭO), 4.02 (ddd, 3 H, JH,H ϭ 9.80, 5.62, 2.28 Hz,
Ј-H ose), 4.30 (m, 2 H, H ϪOϪCH Ϫ), 4.28 (m, 3 H, 6Јb-H ose),
.39(dd, JH,H ϭ 12.32, 5.44 Hz, 3 H, 6Јa-H ose), 5.30 (m, 3 H, 4Ј-
3
f
3
CH
3
3
3
3
Ϫ3
UV/visible (CH
7.2), 592 (4.0), 648 nm (3.8). H NMR (400 MHz, CDCl
δ ϭ Ϫ2.76 (br. s, 2 H, NH pyr), 2.35 (m, 2 H, H ϪCH
s, 9 H, CH tolyl), 2.77 (t, JH,H ϭ 7.1 Hz, 2 H, H ϪCH
.31 (t, JH,H ϭ 6.1 Hz, 2 H, H OϪCH Ϫ), 7.23 (m, 2 H, 3,5-H
Ar), 7.52 (br. d, 6 H, JH,H ϭ 7.8 Hz, 3,5-H tolyl), 8.07 (d, JH,H
2 2
Cl
2
2
5
4
β
2
1
(
3
, 25 °C):
Ϫ), 2.68
2
ϪCϭO),
γ
2
β
2
α
2
(
4
3
γ
α
2
H ose), 5.45 (m, 9 H, 3Ј,2Ј,1Ј-H ose), 7.24 (d, JH,H ϭ 8.50 Hz, 2
H, 2,6-H Ar), 7.35(d, JH,H ϭ 8.32 Hz, 6 H, 3,5-H Ar-ose), 8.07 (d,
ϭ
7
8
.7 Hz, 2 H, 2,6-H Ar), 8.09 (d, JH,H ϭ 7.6 Hz, 6 H, 2,6-H tolyl),
.83 (br. s, 8 H, H pyr) ppm. SM (MALDI): m/z ϭ 759.96 [M
J
H,H ϭ 8.40 Hz, 2 H, 3,5-H Ar), 8.10 (d, JH,H ϭ 8.32 Hz, 6 H, 2,6-
H Ar-ose), 8.82 (d, JH,H ϭ 4.68 Hz, 2 H, H pyr), 8.83 (s, 4 H, H
pyr) 8.86 (d, JH,H ϭ 4.68 Hz, 2 H, H
pyr) ppm. 13C NMR (CDCl
-[2-(3-Ethoxycarbonylpropyloxy)phenyl]-10,15,20-tris(4-methyl- 25 °C): δ ϭ 20.64, 20.67, 20.76, 20.81, 24.8, 30.9, 62.1, 66.9, 68.4,
β
ϩ
β
β
ϩ H] .
β
3
,
5
phenyl)porphyrin (5b): Porphyrin 3b (150 mg, 0.22 mmol, 1 equiv.),
ethyl 4-bromobutyrate (159 mL, 1.1 mmol, 5 equiv.) and K CO
615 mg, 4.4 mmol, 20 equiv.) afforded pure product 5b (158 mg,
71.36, 72.27, 72.86, 99.12, 112.7, 115.1, 119.1, 119.2, 120.2, 131.0,
134.5, 135.5, 135.6, 137.2, 146.5, 156.6, 158.7, 169.7, 170.3, 170.6,
178.0 ppm. SM (MALDI): m/z ϭ 1472.22 [M ϩ H] .
2
3
ϩ
(
Ϫ3
8
5%). R
f 3 2 2
ϭ 0.66 (CHCl ). UV/visible (CH Cl ): λ (ε, ϫ 10 ) ϭ
1
4
20 (391.0), 516 (13.4), 552 (8.1), 592 (4.6), 648 nm (2.8). H NMR 10,15,20-Tris[4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β-
D
-glucopyranosyloxy)-
(
J
400 MHz, CDCl
3
, 25 °C): δ ϭ Ϫ2.72 (s, 2 H, NH pyr.), 0.73 (t,
phenyl]-5-[2-(3-tert-butoxycarbonylpropyloxy)phenyl]porphyrin (6b):
Porphyrin 4b (100 mg, 0.06 mmol, 1 equiv.), compound 1 (66 mg,
H,H
ϭ
7.20 Hz,
3
H, CH
3
ethyl), 1.30 (m,
4
H,
H
β,γ
ϪCH
2
ϪCH
2
ϪCϭO), 2.69 (s, 9 H, CH
3
tolyl), 3.59 (q, JH,H
ϭ
0.3 mmol, 5 equiv.) and K
ethyl), 3.91 (br. t, JH,H ϭ 5.20 Hz,, 2 H, forded pure product 6b (88 mg, 82%) R
2
CO
3
(165 mg, 1.2 mmol, 20 equiv.) af-
ϭ 0.49 (CHCl /EtOH,
2 2
Cl ): λ (ε, ϫ 10 ) ϭ 420 (436.1), 516 (17.8),
7.20 Hz, 2 H, CH
2
f
3
Ϫ3
ϪCH
2
Ϫ), 7.30 (br. d, JH,H ϭ 8.00 Hz, 1 H, 4-H Ar), 7.34 (br. t, 95:5). UV/visible (CH
552 (8.9), 591 (5.7), 648 nm (5.2). H NMR (400 MHz, CDCl
H tolyl), 7.73 (dt, JH,H ϭ 8.40 Hz Ϫ 1.60 Hz, 1 H, 5-H Ar), 8.02 °C): δ ϭ Ϫ2.78 (s, 2 H, NH), 1.01 (s, 9 H, CH tert-butyl), 1.27
dd, JH,H ϭ 7.60 Hz Ϫ 1.60 Hz, 1 H, 3-H Ar), 8.10 (br. d, JH,H
(m, 2 H, H ϪCH Ϫ), 1.31 (t, JH,H ϭ 5.16 Hz, 2 H, H ϪCHϪCϭ
O), 2.10 (m, 27 H, CH ), 2.21 (s, 6 H, CH ), 2.21 (s, 3 H, CH ),
pyr) ppm. 3.92 (t, JH,H ϭ 5.68 Hz, 2 H, H ϪCHϪ), 4.05 (ddd, 3 H, JH,H
1
JH,H ϭ 7.20 Hz, 1 H, 6-H Ar), 7.53 (d, JH,H ϭ 7.60 Hz, 6 H, 3,5-
3
, 25
3
(
ϭ
β
2
γ
8
8
.00 Hz, 6 H, 2,6-H tolyl), 8.77 (d, JH,H ϭ 4.80 Hz, 2 H, H
.83 (d, JH,H ϭ 4.76 Hz, 2 H, H pyr), 8.84 (s, 4 H, H
β
pyr),
3
3
3
α
ϭ
β
β
ϩ
SM (MALDI): m/z ϭ 787.94 [M ϩ H] .
-[2-(3-Carboxypropyloxy)phenyl]-10,15,20-tris(4-methylphenyl)-
porphyrin (7b): The saponification of 5b (carried out on 120 mg)
gave porphyrin 7b in a 97% yield. R ϭ 0.49 (CHCl /EtOH, 95:5).
): λ (ε, ϫ 10 ) ϭ 420 (388.6), 517 (15.7), 553
9.8), 592 (4.9), 648 nm (4.2). SM (MALDI): m/z ϭ 759.86 [M
10.2, 7.1, 2.08 Hz, 5Ј-H ose), 4.30 (br. d, JH,H ϭ 12.3 Hz, 3 H, 6Јb-
H ose), 4.42 (dd, JH,H ϭ 12.38, 5.40 Hz, 3 H, 6Јa-H ose), 5.30 (br.
t, JH,H ϭ 9.32 Hz, 3 H, 4Ј-H ose), 5.45 (m, 9 H, 3Ј,2Ј,1Ј-H ose),
5
7.33 (m, 2 H, 4,6-H Ar), 7.37 (br. d, JH,H ϭ 8.4 Hz, 6 H, 3,5-H
f
3
Ar-ose), 7.75 (d t, 1 H, JH,H ϭ 8.06, 1.6 Hz, 5-H Ar), 8.00 (dd,
Ϫ3
2 2
UV/visible (CH Cl
JH,H ϭ 7.36, 1.56 Hz, 1 H, 3-H Ar), 8.12 (m, 6 H, 2,6-H Ar-ose),
(
1
3
8
.80 (m, 4 H, H
, 25 °C): δ ϭ 20.65, 20.69, 20.78, 20.83, 24.16, 27.7, 31.0,
62.11, 67.4, 68.4, 71.3, 72.3, 72.8, 99.2, 112.1, 115.1, 115.5, 119.6,
phenyl]-5-[4-(3-tert-butoxycarbonylpropyloxy)phenyl]porphyrin (6a): 119.7, 120.5, 130.5, 131.3, 135.0, 135.6, 136.9, 137.0, 146.5, 155.6,
β β
pyr), 8.83 (br. s, 4 H, H pyr) ppm. C NMR
ϩ
ϩ H] .
(CDCl
3
1
0,15,20-Tris[4-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β-D-glucopyranosyloxy)-
Eur. J. Org. Chem. 2003, 1486Ϫ1493
1491