|Budget Amount *help
¥5,800,000 (Direct Cost : ¥5,800,000)
Fiscal Year 1997 : ¥2,700,000 (Direct Cost : ¥2,700,000)
Fiscal Year 1996 : ¥3,100,000 (Direct Cost : ¥3,100,000)
(1) The distinctive structural features of P450 are the unusual thiolate coordination to heme. We have succeeded in the preparation of the first synthetic thiolato-iron porphyrin (SR complex) which can keep its original structure during catalytic oxidation. Experiments using SR,directed toward relative effect of axial ligand, have revealed that a thiolate ligand greatly accelerates the rate of the O-O bond cleavage, and its heterolysis even in highly hydrophobic media. Further, we have established that the thiolate ligand has a marked influence on the reactivity of high-valent iron-oxo porphyrin intermediate.
(2) Heteroaromatic N-oxides were found to be excellent oxidants in the presence of ruthenium porphyrin.2,6-Disubstituted pyridine N-oxides plus a catalytic amount of Ru porphyrin oxidized olefins, sulfides, and allyl or benzyl alcohols to afford epoxides, sulfoxides, and aldehydes, respectively, in high yields. The system in the presence of these acids effectively oxidized unactivated alkanes and arenes to give alcohols (or ketones) and p-quinones in high yields with high selectivity and an extremely high catalyst turnover number (up to 1.2 x 10^5). This is the first example that a heteroaromatic N-oxide works as an oxidant for hydrocarbon without photoactivation.
(3) P450 mimics were applied to drug metabolism studies. The uses of model systems were effective for one-step preparation of unstable metabolic intermediates, "candidate metabolites", and for the discovery of novel modes of metabolism. In the chemical system, gamma, delta-or beta, gamma-unsaturated carboxylic acids are converted to the delta-or beta-hydroxy-gamma-lactone compound, respectively in high yield with high stereoselectivity.