Porphyrin-mediated oxidation

It is useful to note that these are rare examples of porphyrin-mediated oxidation of sophisticated pharmaceutical entities. The reactions described above are generally applicable and have been used in our laboratories to achieve hydroxylation and N-demethylation on numerous other substrates. The hydroxy metabolite and the desmethyl derivative were usually difficult to synthesize by conventional organic chemistry methods. 

The synthesis of the aromatic analog of [24]tetrathiaporphyrin-(2.2.2.2), namely tetrathia[22]porphyrin-(2.2.2.2) 4.169, has also recently been recorded. It was achieved via the DDQ-mediated oxidation of the dihydro tetrathiaporphyr-inogen-(2.2.2.2) 4.168, a species that was in turn prepared in 0.7% yield from a McMurry-type cyclocondensation of 2,5-thiophenedicarboxaldehyde 4.164 (Scheme 4.4.7). It is of interest to note that the isolation of the dihydro compound 4.168 from this reaction sequence is in direct contrast to the observations of Cava and coworkers discussed above. While it is presumed that 4.168 arises as a result of the highly reductive reaction conditions, it remains unclear as to why these disparate results were obtained. This discrepancy is perhaps attributable to the use of slightly different McMurry-type reductive coupling reaction conditions. Such differences may also account for the fact that Cava and coworkers report a 38% yield of the... 

Electron transfer effects in porphyrins are of biological relevance for a number of reasons, not least in the understanding of mechanisms involved in photodynamic therapy. Studies reported include fluorescence quenching of porphyrins by oxidants such as p-benzoquinone , photoinduced electron transfer of porphyrin-acceptor molecules in solid state °, and ps experiments on quinone substituted monometallic porphyrin dimer which show evidence for super-exchange mediated electron transfer in photosynthetic systems . 

Water-soluble iron(iii) porphyrins and phosphotungstic acid in [G4GiIm]BF4 are effective catalysts for the H2O2-mediated oxidation of the G=NOH bond in V-hydroxyarginine and other oximes (Scheme 24). ... 

A combination of PQQ derivatives with transition metals leads to form the efficient redox systems. Dropwise addition of terminal olefin to the solution of PdCl2 (0.1 molar equiv.), trimethyl ester of PQQ, (PQQTME, 0.1 molar equiv.) and H2O in DMF under molecular oxygen results in the formation of 2-alkanone (Scheme 3.2). It should be noted that PQQTME constitutes a catalytic redox cycle. The orthoqui-none function appears to reoxidize the reduced palladium species generated in situ. Use of 1,7- or 1,10-phenanthrolinequinone gives a poor result maybe due to the coordination of paUadium(II) species towards the pyridine moiety opposite to the quinone group [5]. Mediation ofp-benzoquinone in the palladium-catalyzed oxidation reactions has been reported to require electrochemical or cobalt porphyrin catalyzed oxidation of the quinol [6-8]. The above-mentioned results provide an example for efficient redox systems of coenzyme derivatives with transition metals, which is demonstrated to be synthetically useful. 

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

In order to explain their high activity and stability it was postulated that polyhalogenation of the porphyrin ring system not only stabilizes the latter towards oxidative destruction but also stabilizes the oxoiron intermediate with respect to p-oxo dimer formation. In principle, it should also be possible to design stable solid catalysts capable of mediating analogous selective oxidations in the liquid phase. 

It is noteworthy that siroheme is present in the enzymes responsible for catalyzing two out of only three known six-electron processes, and accordingly it is of great interest to try and identify any feature in siroheme that makes it particularly suitable for the mediation of multielectron transfer. A comparison of octaethylporphyrin, octaethylchlorin and octaethylisobacteriochlorin complexes of iron shows that redox potentials and vco of Fe(P)L(CO) and Fe(P)L(CO)2 were nearly independent of the porphyrin. The property that was most dependent upon the macrocycle structure was the potential for ring-based oxidation which increased in the order OEiBC < OEC < OEP.734... 

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