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Synlett 2010(3): 395-398  
DOI: 10.1055/s-0029-1219355
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Glycoporphyrins Using Trichloroacetimidates as Glycosyl Donors

Daniel Aichera,b, Arno Wiehec, Christian B. W. Stark*a
a Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax: +49(341)9736599; e-Mail: cstark@uni-leipzig.de;
b Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
c biolitec AG, Winzerlaer Str. 2, 07745 Jena, Germany
Further Information

Publication History

Received 7 August 2009
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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23

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.

24

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.