PDF herunterladen
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)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

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

    References and Notes

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