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
Weitere Informationen

Publikationsverlauf

Received 7 August 2009
Publikationsdatum:
25. Januar 2010 (online)

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.

    References and Notes

  • 1a Ali H. van Lier JE. Chem. Rev.  1999,  99:  2379 
  • 1b Macdonald IJ. Dougherty TJ. J. Porphyrins Phthalocyanines  2001,  5:  105 
  • 2 Adams KR. Berenbaum MC. Bonnett R. Nizhnik AN. Salgado A. Vallés MA. J. Chem. Soc., Perkin Trans. 1  1992,  1465 
  • 3 Dukh M. Šaman D. Lang K. Pouzar V. Černý I. Drašar P. Král V. Org. Biomol. Chem.  2003,  1:  3458 
  • 4 Sharon N. Lis H. Science  1989,  246:  227 
  • 5a Laville I. Pigaglio S. Blais J.-C. Loock B. Maillard P. Grierson DS. Blais J. Bioorg. Med. Chem.  2004,  12:  3673 
  • 5b Hirohara S. Obata M. Ogata S. Ohtsuki C. Higashida S. Ogura S. Okura I. Takenaka M. Ono H. Sugai Y. Mikata Y. Tanihara M. Yano S. J. Photochem. Photobiol. B: Biol.  2005,  78:  7 
  • For recent reviews on the impact and implications of natural product hybrids, see:
  • 6a Mehta G. Singh V. Chem. Soc. Rev.  2002,  31:  324 
  • 6b Tietze LF. Bell HP. Chandrasekhar S. Angew. Chem. Int. Ed.  2003,  42:  3996 ; Angew. Chem. 2003, 115, 4128
  • 6c Gademann K. Chimia  2006,  60:  841 
  • 7 Desroches M.-C. Bautista-Sanchez A. Lamotte C. Labeque B. Auchère D. Farinotti R. Maillard P. Grierson DS. Prognon P. Kasselouri A. J. Photochem. Photobiol. B: Biol.  2006,  84:  56 
  • 8a Cavaleiro JAS. Tomé JPC. Faustino MAF. Top. Heterocycl. Chem.   Vol. 7:  Springer; Berlin / Heidelberg: 2007.  p.179 
  • 8b Zheng X. Pandey RK. Anticancer Agents Med. Chem.  2008,  8:  241 
  • 9 Fuhrhop J.-H. Demoulin C. Boettcher C. Koening J. Siggel U. J. Am. Chem. Soc.  1992,  114:  4159 
  • 10a Pasetto P. Chen X. Drain CM. Franck RW. Chem. Commun.  2001,  81 
  • 10b Ahmed S. Davoust E. Savoie H. Boa AN. Boyle RW. Tetrahedron Lett.  2004,  45:  6045 
  • 11a Casiraghi G. Cornia M. Zanardi F. Rassu G. Ragg E. Bortolini R. J. Org. Chem.  1994,  59:  1801 
  • 11b Štěpanék P. Dukh M. Šaman D. Moravcová J. Knie˛o L. Monti D. Venanzi M. Mancini G. Drašar P. Org. Biomol. Chem.  2007,  5:  960 
  • 12a Fülling G. Schröder D. Franck B. Angew. Chem., Int. Ed. Engl.  1989,  28:  1519 ; Angew. Chem. 1989, 101, 1550
  • 12b Oulmi D. Maillard P. Guerquin-Kern J.-L. Huel C. Momenteau M. J. Org. Chem.  1995,  60:  1554 
  • 12c Hombrecher HK. Schell C. Thiem J. Bioorg. Med. Chem. Lett.  1996,  6:  1199 
  • 12d Tomé JPC. Neves MGPMS. Tomé AC. Cavaleiro JAS. Mendonça AF. Pegado IN. Duarte R. Valdeira ML. Bioorg. Med. Chem.  2005,  13:  3878 
  • 13a Zheng G. Graham A. Shibata M. Missert JR. Oseroff AR. Dougherty TJ. Pandey RK. J. Org. Chem.  2001,  66:  8709 
  • 13b Laville I. Pigaglio S. Blais J.-C. Doz F. Loock B. Maillard P. Grierson DS. Blais J. J. Med. Chem.  2006,  49:  2558 
  • 14a Krohn K. Thiem J. J. Chem. Soc., Perkin Trans. 1  1977,  1186 
  • 14b Halazy S. Berges V. Ehrhard A. Danzin Z. Bioorg. Chem.  1990,  18:  330 
  • 15 da Silva FdC. Ferreira VF. de Souza MCBV. Tomé AC. Neves MGPMS. Silva AMS. Cavaleiro JAS. Synlett  2008,  1205 
  • 16a Pougny JR. Jacquinet JC. Nassr M. Duchet D. Milat ML. Sinay P. J. Am. Chem. Soc.  1977,  99:  6762 
  • 16b Schmidt RR. Michel J. Angew. Chem., Int. Ed. Engl.  1980,  19:  731 ; Angew. Chem. 1980, 92, 763
  • 17 Bonnett R. White RD. Winfield U.-J. Berenbaum MC. Biochem. J.  1989,  261:  277 
  • 18 Lindsey JS. Schreimann IC. Hsu HC. Kearney PC. Marguerettaz AM. J. Org. Chem.  1987,  52:  827 
  • 19 For the preparation of glucosyl trichloroacetimidates, see: Lindhorst TK. Essentials of Carbohydrate Chemistry and Biochemistry   2nd ed.:  Wiley-VCH; Weinheim: 2003. 
  • 20 Cammidge AM. Lifsey KM. Tetrahedron Lett.  2000,  41:  6655 
  • 21 For the preparation of galactosyl trichloroacetimidates, see: Schmidt RR. Stumpp M. Liebigs Ann. Chem.  1983,  1249 
  • 22 Laville I. Figueiredo T. Loock B. Pigaglio S. Maillard P. Grierson DS. Carrez D. Croisy A. Blais J. Bioorg. Med. Chem.  2003,  11:  1643 
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.