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Synlett 2005(5): 0857-0859  
DOI: 10.1055/s-2005-863736
LETTER
© Georg Thieme Verlag Stuttgart · New York

Porphyrins in 1,3-Dipolar Cycloadditions with Sugar Azomethine Ylides. Synthesis of Pyrrolidinoporphyrin Glycoconjugates

Ana M. G. Silvaa, Augusto C. Toméa, Maria G. P. M. S. Nevesa, José A. S. Cavaleiro*a, Daniela Perroneb, Alessandro Dondoni*b
a Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal
e-Mail: jcavaleiro@dq.ua.pt;
b Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, 44100 Ferrara, Italy
e-Mail: adn@dns.unife.it;
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Publikationsverlauf

Received 22 November 2004
Publikationsdatum:
09. März 2005 (online)

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Abstract

Pyrrolidine-fused chlorins carrying an N- or C-linked ­galactose residue were prepared by 1,3-dipolar cycloadditions of meso-tetrakis(pentafluorophenyl)porphyrin to galactose-substi­tuted azomethine ylides.

Key words

porphyrins - chlorines - cycloadditions - ylides - glycosides

9

Functionalized fullerenes have been reported to behave as HIV protease inhibitors, antioxidants, cytotoxics, and photodynamic agents for DNA cleavage. See ref.8 and references cited therein.

12

Procedure for the Synthesis of Chlorins 6a and 6b. To a refluxing solution of 5 (30.0 mg, 0.03 mmol) and N-methylglycine (11.0 mg, 0.12 mmol) in toluene (4 mL), in the presence of molecular sieves (2 g) and under nitrogen, was added dropwise during 4 h a solution of the aldehyde 3 (80.0 mg, 0.31 mmol) in toluene (1 mL). After the addition was complete, the reaction mixture was refluxed for an additional period of 15 min. The mixture was cooled and filtered. The filtrate was evaporated to dryness and purified by flash chromatography in CH2Cl2-EtOAc (9:1). The first fraction was the unchanged starting porphyrin 5 (11.6 mg, 39%). The second one was the minor chlorin (7.4 mg, 19% yield) and the third one was the major chlorin (12.6 mg, 32% yield). The last fraction was the chlorin 8 (2.6 mg, 8% yield).

13

Successful 1,3-dipolar cycloaddition of porphyrins to the azomethine ylide 4 is greatly dependent on the dipolaro-philic character of the former, which in turn is enhanced by the presence of electron-withdrawing groups. We observed that only the sugar-free cycloadduct was formed by the use of meso-tetraphenylporphyrin while the reaction of 2-nitro-5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin lead to a complex mixture of pyrrolidino-porphyrin glycoconjugates and no formation of the side-product of type 8.

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Spectroscopic data for the major chlorin: 1H NMR (400 MHz, CDCl3): δ = -1.78 and 1.71 (2 s, 2 H, NH), 1.40, 1.42, 1.53, 1.55 and 1.98 (5 s, 15 H, 5 × CH3), 2.79 (dd, 1 H, J = 9.8 and 3.9 Hz, H-23 trans ), 3.46 (dd, 1 H, J = 9.8 and 9.1 Hz, H-23 cis ), 3.90 (d, 1 H, J = 6.2 Hz, H-21), 3.95 (d, 1 H, J = 6.2 Hz, H-5-sugar), 4.32 (dd, 1 H, J = 4.8 and 2.0 Hz, H-2-sugar), 4.39 (d, 1 H, J = 7.7 Hz, H-4-sugar), 4.64 (dd, 1 H, J = 7.7 and 2.0 Hz, H-3-sugar), 5.28 (ddd, 1 H, J = 9.1, 8.2 and 3.9 Hz, H-3), 5.33 (d, 1 H, J = 4.8 Hz, H-1-sugar), 5.62 (d, 1 H, J = 8.2 Hz, H-2), 8.36 and 8.42 (2 d, 2 H, J = 4.8 Hz, H-β), 8.46 (AB, 2 H, H-β), 8.67 and 8.70 (2 d, 2 H, J = 4.8 Hz, H-β). MS (LSIMS): 1260 [M + H]+, 1259 [M+], 1031 [M - C11H17O5 + H]+, 975 [porphyrin 5 + H]+. UV/Vis (CH2Cl2): λmax (log ε) = 653 (4.66), 599 (3.69), 505 (5.19), 408 (5.24) nm. Anal. Calcd for C58H33F20N5O5: C, 55.29; H, 2.64; N, 5.56. Found: C, 55.32; H, 2.70; N, 5.42.

15

Spectroscopic data for the minor chlorin: 1H NMR (400 MHz, CDCl3): δ = -1.87 and 1.82 (2 s, 2 H, NH), 1.31, 1.40, 1.50, 1.55 and 1.57 (5 s, 15 H, 5 × CH3), 3.06 (dd, 1 H, J = 12.1 and 3.5 Hz, H-23 trans ), 3.50-3.54 (m, 1 H, H-23 cis ), 3.57 (d, 1 H, J = 10.2 Hz, H-5-sugar), 3.67 (d, 1 H, J = 10.2 Hz, H-21), 4.32 (dd, 1 H, J = 4.8 and 2.1 Hz, H-2-sugar), 4.43 (dd, 1 H, J = 8.2 and 1.5 Hz, H-4-sugar), 4.54 (dd, 1 H, J = 8.2 and 2.0 Hz, H-3-sugar), 5.04 (dt, 1 H, J = 8.4 and 3.5 Hz, H-3), 5.43 (d, 1 H, J = 4.8 Hz, H-1-sugar), 5.50 (d, 1 H, J = 8.4 Hz, H-2), 8.40 and 8.44 (2 d, 2 H, J = 4.8 Hz, H-β), 8.48 and 8.50 (2 d, 2 H, J = 4.8 Hz, H-β), 8.71 (AB, 2 H, H-β). MS (LSIMS): 1260 [M + H]+, 1259 [M+], 1031 [M - C11H17O5 + H]+, 975 [porphyrin 5 + H]+. UV/Vis (CH2Cl2): λmax (log ε) = 652 (4.60), 598 (3.65), 505 (4.13), 406 (5.18) nm. HRMS-FAB (exact mass): m/z calcd for C58H34N5O5F20 [M + H]+: 1260.2235; found: 1260.2202.

18

Procedure for the Synthesis of Chlorin 11.
A solution of N-galactosyl glycine 9 (23.2 mg, 0.06 mmol) and K2CO3 (17.0 mg, 0.12 mmol) in toluene (2.5 mL) was stirred at r.t. during 5 min. Paraformaldehyde (5.0 mg, 0.15 mmol) and porphyrin 5 (15.0 mg, 0.015 mmol) were then added and the reaction mixture was heated at reflux, under nitrogen, during 2 h. The mixture was cooled, filtered and washed with CH2Cl2 (10 mL). The solvents were evaporated to dryness and the residue was purified by flash chromatography using CH2Cl2-EtOAc (30:1) as eluent. The unchanged starting porphyrin 5 (11.9 mg, 79%) was the first fraction, followed by chlorin 11 (3.7 mg, 19% yield).

19

Spectroscopic data for chlorin 11: 1H NMR (300 MHz, CDCl3): δ = -1.82 (s, 2 H, NH), 1.30, 1.39, 1.46, 1.55 (4 s, 12 H, 4 × CH3), 2.41-2.50 (m, 2 H, H-21 or H-23), 2.52 and 2.70 (2 d, 2 H, J = 12.8 Hz, CH2-Gal), 3.34-3.39 and 3.45-3.51 (2 m, 2 H, H-21 or H-23), 3.85 (d, 1 H, J = 7.6 Hz, H-5-Gal), 4.15 (d, 1 H, J = 7.6 Hz, H-4-Gal), 4.34 (dd, 1 H, J = 5.4 and 2.2 Hz, H-2-Gal), 4.59 (dd, 1 H, J = 7.6 and 2.2 Hz, H-3-Gal), 5.25-5.34 (m, 2 H, H-2, H-3), 5.57 (d, 1 H, J = 5.2 Hz, H-1-Gal), 8.41 and 8.48 (2 d, 2 H, J = 4.3 Hz, H-β), 8.52 (s, 2 H, H-12, H-13), 8.74 (AB, 2 H, H-β). MS (LSIMS): 1260 [M + H]+, 1259 [M+], 1031 [M - C11H17O5 + H]+, 975 [porphyrin 5 + H]+. UV/Vis (CH2Cl2): λmax
(log ε) = 651 (4.59), 597 (3.61), 504 (4.12), 406 (5.16) nm. Anal. Calcd for C58H33F20N5O5: C, 55.29; H, 2.64; N, 5.56. Found: C, 55.38; H, 2.64; N, 5.77.