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DOI: 10.1055/s-0029-1219355
Synthesis of Glycoporphyrins Using Trichloroacetimidates as Glycosyl Donors
Publication History
Publication Date:
25 January 2010 (online)
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Abstract
The trichloroacetimidate method has been utilized for the glycosylation of porphyrins. The corresponding glycoconjugates were obtained rapidly, in high yields, and excellent purity. A three-step sequence using well-matched (Lewis) acids was found to be highly effective and reliable.
Key words
porphyrins - glycosylations - glycoconjugates - antitumor agents - photodynamic therapy
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References and Notes
Typical Glycosylation
Procedure
Zn(II) 5-(3-hydroxyphenyl)-10,15,20-triphenylporphyrin (2a, 100 mg, 0.14 mmol) was dissolved in
dry CH2Cl2 (20 mL) under an argon atmosphere.
Then 2,3,4,6-tetra-O-acetyl-β-d-gluco-pyranosyl trichloroacetimidate
(130 mg, 0.26 mmol, 1.85 equiv) or 2,3,4,6-tetra-O-acetyl-α-d-galacto-pyranosyl trichloroacetimidate
(350 mg, 0.70 mmol, 5.0 equiv) was added in three portions followed
by BF3˙OEt2 (5.0 µL, 0.04
mmol). After stirring for 15 min for glucosyl-ation or 120 min for
galactosylation the mixture was transferred to a separatory funnel.
The organic layer was washed with H2O (2 × 50
mL), and the solvent was evaporated under reduced pressure. The
residue was dissolved in THF (20 mL) and HCl (25%, 0.5
mL) were added. After stirring for 10 min H2O (50 mL)
and CH2Cl2 (75 mL) were added. The organic
layer was separated and washed with H2O (2 × 50
mL). After drying with Na2SO4 the solvent
was evaporated under reduced pressure. Further purification was
achieved by flash chromatography using CH2Cl2-EtOAc
(95:5) as the eluent. The analytically pure product was obtained
as a violet crystalline solid after recrystallization from CH2Cl2-MeOH.
5-[3-(2,3,4,6-Tetraacetyl-β-
d
-glucosyl)phenyl]-10,15,20-triphenylporphyrin
(3a)
Yield 123 mg, 89%; mp 205 ˚C. ¹H
NMR (500 MHz, CDCl3): δ = -2.70
(m, 2 H, NH), 1.37 (s, 3 H, OAc), 2.02 (s, 3 H, OAc), 2.07 (s, 3
H, OAc), 2.12 (s, 3 H, OAc), 3.83 (ddd, J = 2.4,
5.8, 10.0 Hz, 1 H, H-5‘ose’), 4.08 (dd, J = 2.4, 12.2 Hz,
1 H, H-6A‘ose’), 4.20 (dd, J = 5.8, 12.2
Hz, 1 H, H-6B‘ose’), 5.20 (dd, J = 9.1, 10.0
Hz, 1 H, H-4‘ose’), 5.32 (dd, J = 9.1,
9.1 Hz, 1 H, H-3‘ose’), 5.35 (d, J = 7.8
Hz, 1 H, H-1‘ose’), 5.40 (dd, J = 7.8,
9.1 Hz, 1 H, H-2‘ose’), 7.42-7.45 (m,
1 H, Ar), 7.66-7.69 (m, 1 H, Ar), 7.74-7.81 (m,
9 H, Ph), 7.88-7.89 (m, 1 H, Ar), 7.95-7.97 (m,
1 H, Ar), 8.20-8.26 (m, 6 H, Ph), 8.85-8.89 (m,
8 H, β-pyrrole-H). ¹³C NMR (126
MHz, CDCl3): δ = 19.83,
20.45, 20.53, 20.63, 61.98, 68.44, 71.42, 72.29, 72.86, 99.41, 116.75,
118.97, 120.28, 120.30, 120.44, 122.95, 126.69, 127.68, 127.78,
129.94, 131.16, 134.54, 142.15, 143.88, 155.41, 169.28, 170.11, 170.27.
ESI-HRMS: m/z calcd for C58H49N4O10
+ [M + H]+: 961.3443;
found: 961.3481. UV/vis (CH2Cl2): λmax (ε) = 417 (298600),
515 (18400), 549 (10700), 591 (8700), 646 (6400) nm.
5-[3-(2,3,4,6-Tetraacetyl-β-
d
-galactosyl)phenyl]-10,15,20-triphenylporphyrin
(4)
Yield 116 mg, 84%; mp 169 ˚C. ¹H
NMR (500 MHz, CDCl3): δ = -2.71
(s, 2 H, NH), 1.20 (s, 3 H, OAc), 2.00 (s, 3 H, OAc), 2.10 (s, 3
H, OAc), 2.16 (s, 3 H, OAc), 4.02 (ddd, J = 1.1,
6.4, 6.4 Hz, 1 H, H-5‘ose’), 4.11-4.14
(m, 2 H, H-6‘ose’), 5.17 (dd, J = 3.4,
10.4 Hz, 1 H, H-3‘ose’), 5.35 (d, J = 8.0 Hz,
1 H, H-1‘ose’), 5.44 (dd, J = 1.1,
3.4 Hz, 1 H, H-4‘ose’), 5.64 (dd, J = 8.0, 10.4
Hz, 1 H, H-2‘ose’), 7.47-7.49 (m, 1 H,
Ar), 7.68-7.71 (m, 1 H, Ar), 7.77-7.83 (m, 9 H,
Ph), 7.94-7.95 (m, 1 H, Ar), 7.97-8.00 (m, 1 H,
Ar), 8.23-8.27 (m, 6 H, Ph), 8.87-8.90 (m, 8 H, β-pyrrole-H). ¹³C
NMR (126 MHz, CDCl3): δ = 19.72,
20.48, 20.52, 20.71, 61.45, 67.07, 68.86, 70.92, 71.33, 99.98, 116.70,
118.99, 120.24, 120.28, 120.42, 123.07, 126.68, 127.65, 127.76,
129.91, 131.09, 134.54, 142.14, 143.85, 155.42, 169.32, 169.96, 170.02,
170.09. ESI-HRMS: m/z calcd
for C58H49N4O10
+
[M + H]+:
961.3443; found: 961.3411. UV/vis (CH2Cl2): λmax (ε) = 417
(308600), 515 (20900), 549 (16300), 591 (13600), 646 (10800) nm.
Typical Procedure
for Deacetylation
To a stirred solution of 5-[3-(2,3,4,6-tetraacetyl-β-d-glucosyl)phenyl]-10,15,20-triphenylporphyrin
(3a, 50 mg, 0.05 mmol) in dry THF-MeOH
(1:1, 10 mL) under an argon atmosphere a solution of sodium methanolate
in dry MeOH (1.5 mL, 0.02 N) was added. After 2 h the solvent was evaporated
under reduced pressure, and the crude product was purified by flash
chromatography using CH2Cl2-MeOH (9:1)
as the eluent. The pure product was obtained as a violet crystalline
solid after recrystallization from CH2Cl2-MeOH aq.
5 (3-β-
d
-Glucosylphenyl)-10,15,20-triphenylporphyrin (5a)
Yield
40 mg, 97%, mp 160 ˚C. ¹H
NMR [700 MHz, (CD3)2SO]: δ = -2.90
(s, 2 H, NH), 3.22-3.26 (m, 1 H, H‘ose’),
3.31-3.38 (m, 3 H, H‘ose’), 3.47-3.51
(m, 1 H, H-6A‘ose’), 3.68-3.71
(m, 1 H, H-6B‘ose’), 4.57 (dd, J = 5.9, 5.9
Hz, 1 H, OH-6‘ose’), 5.01 (d, J = 5.3
Hz, 1 H, OH‘ose’), 5.11 (d, J = 5.1
Hz, 1 H, OH‘ose’), 5.22 (d, J = 7.6
Hz, 1 H, H-1‘ose’), 5.44 (d, J = 4.9
Hz, 1 H, OH‘ose’), 7.53-7.55 (m, 1 H,
Ar), 7.72-7.75 (m, 1 H, Ar), 7.80-7.87 (m, 1 H,
Ar, 9 H, Ph), 7.91-7.92 (m, 1 H, Ar), 8.20-8.24
(m, 6 H, Ph), 8.80-8.96 (m, 8 H, β-pyrrole-H). ¹³C
NMR [176 MHz, (CD3)2SO]: δ = 61.13,
70.17, 73.89, 77.06, 77.47, 100.85, 116.29, 120.01, 120.51, 120.58,
122.87, 127.47, 128.59, 129.00, 134.72, 141.66, 142.87, 156.39.
ESI-HRMS:
m/z calcd
for C50H41N4O6
+ [M + H]+:
793.3021; found: 793.2900. UV/vis (CH2Cl2): λmax (ε) = 417
(333600), 515 (22800), 549 (16800), 591 (13900), 646 (10700) nm.