UBC Theses and Dissertations

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UBC Theses and Dissertations

Syntheses of selected heme protein model compounds Morgan, Brian D.


Strapped porphyrins may be defined as those compounds in which some bridging group is covalently attached to opposite edges of the porphyrin macrocycle. This class of compound has been extensively studied as models for the active sites of heme proteins such as hemoglobins, cytochrome P450 etc. Two avenues of approach to the synthesis of strapped porphyrins have been used. The strap may be covalently attached to opposite edges of a preformed porphyrin, or the two halves of the porphyrin macrocycle may be assembled at each, end of the strap with a final intramolecular cyclization fitting the strap into place. The latter approach has been adopted here to provide a general route to those strapped porphyrins bearing functional groups in the bridging straps. Compounds 87a, 87b and 118a, 118b have been prepared as possible models for cytochrome c and catalase, while the porphyrin-quinone compounds 143a, 143b may be used to study electron transfer in donor/acceptor complexes. The syntheses of the various strapped porphyrins all originate from the α-free-iodoalkyl pyrroles 44, 64 which, are readily available via Friedel-Crafts acylation of β-free pyrrole 1, followed by reduction and iodination of the alkyl chain and modification of the α-methyl group. For the sulfide-strap porphyrins, reaction with, sodium sulfide to give the bis[(pyrrol-3-yl)alkyl]sulfides 75a, 75b formed the strap. Elaboration to the his-dipyrromethanes 77a, 77b provided all the units necessary for porphyrin synthesis. Saponification and decarboxylation followed by high-dilution acid-catalyzed intramolecular cyclization yielded the strapped porphyrins 87a (9-19%) and 87b (10-18%). Exposure to light during work-up is believed to be responsible for the formation of the corresponding sulfoxide-strap porphyrins 88a, 88b. [See Thesis for Diagrams] Conversion of 44 and 64 to the corresponding phosphonium salts 94a, 94b followed by a double Wittig reaction under phase-transfer conditions with either of the dialdehydes 95 or 131 gave the bis-alkenes. Catalytic hydrogenation yielded the bis(pyrrol-3-yl) compounds 113a, 113b and 138a, 138b. Elaboration to the bis-dipyrromethanes was followed by saponification, decarboxylation and intramolecular cyclization to furnish the strapped porphyrins. These relatively unstrained compounds were obtained in good yield: 117a (30-44%), 117b (21-53%), 140a (41-60%), 140b (20-40%). Treatment of the anisole-porphyrin 117a, 117b with boron tribromide furnished the phenol-strapped porphyrin ,118a (76-89%) , 118b (89-95%). Demethylation of the dimethoxybenzene-porphyrin 140a, 140b also with boron tribromide yielded the hydroquinone which was oxidized to the quinone-strapped porphyrin 143a (.82-87%), 143b (70%). An attempt was made to incorporate a suitably substituted imidazole into the bridging strap using the same procedure. However production of the required 1,5-disubstituted imidazole intermediates was hampered by low yields and difficulty in purification. The failure to prepare the necessary imidazole bis-aldehyde 170 led to cancellation of this attempt. All the porphyrins were subjected to elemental analysis, high resolution mass spectrometry, and visible absorption and ¹H- and ¹³C-NMR spectroscopy. A simplistic attempt was made to correlate the spectral characteristics to the structure, length and conformation of the strap. [See Thesis for Diagrams]

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