Synthesis of New Strapped Porphyrins via a Bisdipyrromethane Condensation

Abstract

Two new cationic strapped meso-porphyrins were synthesized via a new route, which consists of the condensation of a bisdipyrromethane with an aldehyde under acidic conditions. One of the strapped porphyrins binds to G-quadruplex DNA.

Key words

strapped porphyrins - condensation - synthesis - meso - bisdipyrromethane

References and Notes

• 1 Redman JE. Sanders JKM. Org. Lett.  2000,  2:  4141 
• 2 Andrioletti B. Ricard D. Boitrel B. New J. Chem.  1999,  23:  1143 
• 3 Gunter MJ. Hockless DCR. Johnston MR. Skelton BW. J. Am. Chem. Soc.  1994,  116:  4810 
• 4a Osuka A. Kobayashi F. Nagata T. Maruyama K. Chem. Lett.  1990,  2:  287 
• 4b Osuka A. Nagata T. Maruyama K. Chem. Lett.  1991,  10:  1687 
• 5a Ikeda T. Asakawa M. Miyake K. Shimizu T. Chem. Lett.  2004,  33:  1418 
• 5b Anelli PL. Ashton PR. Ballardini R. Balzani V. Delgado M. Gandolfi MT. Goodnow TT. Kaifer AE. Philp D. Pietraszkiewicz M. Prodi L. Reddington MV. Slawin AMZ. Spencer N. Stoddart JF. Vicent C. Williams DJ. J. Am. Chem. Soc.  1992,  114:  193 
• 6 Wijesekera TP. Paine JB. Dolphin D. J. Org. Chem.  1988,  53:  1354 

7

Preparation of Compound 4.
To a flask containing 3 (1.5 g, 3.69 mmol) and pyrrole (118 g, 1.65 mol) was added 1.4 equiv of TFA and the flask was left to stir in open air for 15 min. The reaction was quenched with TEA (7.22 g, 71.4 mmol) and then the unreacted pyrrole was evaporated. The resulting brown oil was purified by column chromatography on silica gel (CHCl₃-MeOH, 10:1), yielding 4 quantitatively as a light brown oil. ¹H NMR (500 MHz, CDCl₃): δ = 8.49 (br s, 4 H), 7.21-7.24 (m, 4 H), 6.95-6.92 (m, 2 H), 6.91-6.89 (m, 2 H), 6.87 (s, 4 H), 6.58-6.60 (m, 4 H), 6.06-6.09 (m, 4 H), 5.89-5.90 (m, 4 H), 5.61 (s, 2 H), 4.21-4.23 (m, 4 H), 4.03-4.05 (m, 4 H) ppm. ¹³C NMR (500 MHz cryo, CDCl₃): δ = 155.8, 153.1, 145.7, 132.5, 130.2, 128.2, 121.6, 116.8, 116.6, 112.5, 108.0, 106.4, 67.4, 66.8, 40.4 ppm. HRMS: m/z calcd 639.2971; found: 639.2943 [M + H⁺].
Preparation of Compound 9.
To a flask containing 8 (2.4 g, 4.12 mmol) and pyrrole (236 g, 3.30 mol) was added 1.4 equiv of TFA and the flask was left to stir in open air for 15 min. The reaction was quenched with TEA (7.22 g, 71.4 mmol) and then the unreacted pyrrole was evaporated. The resulting brown oil was purified by column chromatography on silica gel (CHCl₃-MeOH, 10:1), yielding 9 quantitatively as a light green oil. ¹H NMR (500 MHz, CDCl₃): δ = 7.24 (dd, J = 1.6, 7.6 Hz, 2 H), 7.18 (dt, J = 1.6, 7.6, 8.0 Hz, 2 H), 6.91 (dt, J = 0.9, 7.6, 7.6 Hz, 2 H), 6.83 (dd, J = 0.9, 8.0 Hz, 2 H), 6.76 (s, 4 H), 6.62-6.65 (m, 4 H), 6.08-6.10 (m, 4 H), 5.93-5.94 (m, 4 H), 5.66 (s, 2 H), 4.04-4.06 (m, 4 H), 3.94-3.96 (m, 4 H), 3.77-3.79 (m, 4 H), 3.75-3.76 (m, 4 H), 3.70-3.72 (m, 4 H), 3.65-3.67 (m, 4 H) ppm. ¹³C NMR (500 MHz cryo, CDCl₃): δ = 155.8, 152.9, 132.6, 132.0, 130.1, 128.0, 121.4, 116.5, 115.5, 112.4, 107.8, 106.2, 70.8, 70.7, 69.9, 69.7, 67.8, 67.1, 40.5 ppm. HRMS: m/z calcd: 815.3942; found: 815.4121 [M + H⁺].

8

Preparation of Porphyrin 6.
To a stirred solution of 4 (0.50 g, 1.03 mmol) and 4-pyridinecarboxaldehyde (0.22 g, 2.06 mmol) in CH₂Cl₂ (500 mL), under nitrogen at r.t. and in the dark, was added TCA (2.20 g, 13.46 mmol) dissolved in CH₂Cl₂ (10 mL). After reacting for 90 min, TEA (7.22 g, 71.4 mmol) was added followed by DDQ (0.15 g, 0.66 mmol) and the reaction was stirred for an additional 30 min. The solvent was then evaporated in vacuo and purified by preparative TLC (CH₂Cl₂-MeOH, 10:1), yielding 0.9% of porphyrin 6 (7.5 mg) as a purple solid. UV/Vis: λ_max = 418, 518, 556, 602 nm. ¹H NMR (500 MHz, CDCl₃): δ = 8.97 (br s, 4 H), 8.86 (d, J = 4.8 Hz, 4 H), 8.74 (d, J = 4.8 Hz, 4 H), 7.95 (br s, 4 H), 7.83-7.85 (m, 2 H), 7.77-7.81 (m, 2 H), 7.50-7.55 (m, 2 H), 7.20-7.25 (m, 2 H), 3.87-3.85 (m, 4 H), 3.55 (s, 4 H), 2.82-2.84 (m, 4 H), -2.74 (br s, 2 H) ppm. ¹³C NMR (500 MHz cryo, CDCl₃): δ = 159.4, 152.3, 148.2, 134.1, 131.8, 130.2, 129.6, 120.4, 113.4, 69.3, 68.6, 58.6 ppm. As is usual in porphyrin chemistry, many of the quaternary carbon NMR signals are too weak to be seen. HRMS: m/z calcd: 811.3033; found: 811.3044 [M + H⁺].
Preparation of Porphyrin 10.
To a stirred solution of 9 (0.59 g, 0.60 mmol) and 4-pyridinecarboxaldehyde (0.13 g, 1.20 mmol) in CH₂Cl₂ (500 mL), under nitrogen at r.t. and in the dark, was added TCA (2.20 g, 13.46 mmol) dissolved in CH₂Cl₂ (10 mL). After reacting for 90 min, TEA (7.22 g, 71.4 mmol) was added followed by DDQ (0.30 g, 1.32 mmol) and the reaction was stirred for an additional 30 min. The solvent was then evaporated in vacuo and purified by preparative TLC (CH₂Cl₂-MeOH, 10:1), yielding 19% of porphyrin 10 (92.4 mg) as a purple solid. UV/Vis: λ_max = 414, 510, 546, 592 nm. ¹H NMR (500 MHz, CDCl₃): δ = 9.00 (br s, 4 H), 8.83 (d, J = 4.6 Hz, 4 H), 8.74 (d, J = 4.6 Hz, 4 H), 8.13 (br d, 4 H), 7.86 (dd, J = 1.1, 7.9 Hz, 2 H), 7.76 (td, J = 1.6, 7.6, 7.9 Hz, 2 H), 7.43 (d, J = 7.8 Hz, 2 H), 7.38 (td, J = 1.1, 7.8, 7.6 Hz, 2 H), 5.79 (s, 4 H), 4.06 (t, J = 5.2 Hz, 4 H), 3.19 (t, J = 5.2 Hz, 4 H), 2.88-2.90 (m, 4 H), 2.83-2.84 (m, 4 H), 2.79-2.81 (m, 4 H), 2.74-2.77 (m, 4 H) and -2.79 (br s, 2 H) ppm. ¹³C NMR (500 MHz cryo, CDCl₃): δ = 158.4, 152.1, 148.1, 136.1, 130.8, 130.1, 129.3, 119.9, 117.2, 116.5, 115.2, 112.7, 70.2, 70.1, 69.0, 68.6, 67.4 ppm. HRMS: m/z calcd: 987.4081; found: 987.4041 [M + H⁺].

9

Preparation of Porphyrin 7.
The quaternization of the pyridyl groups of porphyrin 6 was achieved by methylation with a large excess of MeI in DMF, at 40 °C for 5 h, yielding quantitatively porphyrin 7.
Preparation of Porphyrin 11.
The quaternization of the pyridyl groups of porphyrin 10 was achieved by methylation with a large excess of MeI in DMF, at 40 °C for 5 h, yielding quantitatively porphyrin 11.

10

Preparation of Porphyrin 1.
Porphyrin 7 was then submitted to an anion-exchange resin with Dowex 1X2-200 in the chloride form, by shaking the dissolved porphyrin in a mixture of acetone-H₂O (3:2) with the exchange resin for approximately 3 h. The resin was then filtered off and washed with H₂O, giving porphyrin 1 in quantitative yields and without any further purification. UV/vis λ_max = 424, 518, 556, 602 nm. ¹H NMR (500 MHz, CD₃CN 80% CD₃OD 20%): δ = 9.06 (d, J = 5.3 Hz, 4 H), 9.02-8.72 (br m, 12 H), 8.51 (dd, J = 1.4, 7.1 Hz, 2 H), 8.88-8.92 (m, 2 H), 7.59 (t, J = 7.1, 8.0 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 2 H), 4.64 (s, 6 H), 3.89-3.91 (m, 4 H), 3.64 (s, 4 H), 2.91-2.90 (m, 4 H) ppm. The NH signals are not present due to exchange with the solvent. ¹³C NMR (500 MHz cryo, CD₃CN 80% CD₃OD 20%): δ = 159.5, 153.2, 144.9, 134.8, 131.9, 121.3, 115.9, 114.4, 69.8, 69.2, 49.2 ppm. HRMS: m/z calcd: 420.1706 [(M - 2 Cl)/2]; found: 420.1709.
Preparation of Porphyrin 2.
Porphyrin 11 was then submitted to an anion-exchange resin with Dowex 1X2-200 in the chloride form, by shaking the dissolved porphyrin in a mixture of acetone-H₂O (3:2) with the exchange resin for approximately 3 h. The resin was then filtered off and washed with H₂O, giving porphyrin 2 in quantitative yields and without any further purification. UV/vis λ_max = 426, 510, 546, 592 nm. ¹H NMR (500 MHz, CD₃NO₂): δ = 9.19 (d, J = 6.7 Hz, 4 H), 9.03 (br s, 4 H), 8.92 (br s, 4 H), 8.89 (br s, 4 H), 7.86-7.91 (m, 4 H), 7.60 (d, J = 7.8 Hz, 2 H), 7.41 (td, J = 0.9, 7.0, 7.8 Hz, 2 H), 5.53 (s, 4 H), 4.81 (s, 6 H), 4.18-4.20 (m, 4 H), 3.30-3.32 (m, 4 H), 2.96-2.97 (m, 4 H), 2.87-2.89 (m, 4 H), 2.79-2.81 (m, 4 H), 2.69-2.71 (m, 4 H), -2.82 (br s, 2 H) ppm. ¹³C NMR (500 MHz cryo, CD₃NO₂): δ = 159.5, 152.8, 144.6, 137.0, 133.8, 131.6, 120.9, 115.9, 113.9, 70.8, 70.7, 69.7, 69.5, 69.4, 69.1 ppm. HRMS: m/z calcd: 508.2231 [(M - 2 Cl)/2]; found: 508.2064.