Oxygen iron-catalyzed synthesis

Iron-Catalyzed Synthesis of Oxygen-Containing Heterocycles... 

A palladium-catalyzed intramolecular cycliza-tion reaction would be a reasonable place to start [67]. This reaction has been carried out in reactor vessel that was open to air There are several approaches to this synthesis that are tolerant to oxygen. Several palladium- and iron-catalyzed reactions actually use oxygen as the terminal oxidant [60, 61]... 

Very recently, Gu, Li, and coworkers described an iron-catalyzed tandem oxidative process for the synthesis of benzoxazoles from easily available substrates, in which an alkyl C(sp )-H bond adjacent to an oxygen atom was directly aminated with a N-H bond (Scheme 9.9) [11]. In addition, excellent functional group tolerance under relatively mUd conditions and great regioselectivity were exhibited. 

Although a variety of oxidizing agents are available for this transformation it occurs so readily that thiols are slowly converted to disulfides by the oxygen m the air Dithiols give cyclic disulfides by intramolecular sulfur-sulfur bond formation An example of a cyclic disulfide is the coenzyme a lipoic acid The last step m the laboratory synthesis of a lipoic acid IS an iron(III) catalyzed oxidation of the dithiol shown... 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

E. coli uses nitrate as a terminal electron acceptor through a respiratory, dissimilatory nitrate reductase whose synthesis is induced when nitrate is provided, and which is repressed by oxygen. Nitrate reductase is discussed with other molybdoenzymes in Section 62.1.9, and catalyzes the reduction of nitrate to nitrite. The enzyme is isolated from the cytoplasmic membrane of E. coli, and contains three subunits (a, j8 and y) although the y-subunit may be absent in some preparations. The -y-subunit is a b-type cytochrome, and the a-subunit is reported to be the catalytic subunit. The enzyme contains a number of iron-sulfur clusters, including a HiPIP and at least two ferredoxins.1054,1437... 

Here the chemical formula is written CH2, which is one-eighth of a typical gasoline molecule (CgHi6). The reaction is catalyzed by a number of metal-based catalysts including iron, cobalt, and nickel. The reactors in which the synthesis takes place operate within a temperature range of 225 to 365°C and at pressures from 0.5 to 4 MPa. It should also be noted that the Fischer-Tropsch reactions produce a wide spectrum of oxygenated compounds such as alcohols. 

Catabolism of tyrosine and tryptophan begins with oxygen-requiring steps. The tyrosine catabolic pathway, shown at the end of this chapter, results in the formation of fumaric acid and acetoaceticacid, Iryptophan catabolism commences with the reaction catalyzed by tryptophan-2,3-dioxygenase. This enzyme catalyzes conversion of the amino acid to N-formyl-kynurenine The enzyme requires iron and copper and thus is a metalloenzyme. The final products of the pathway are acetoacetyl-CoA, acetyl-Co A, formic add, four molecules of carbon dioxide, and two ammonium ions One of the intermediates of tryptophan catabolism, a-amino-P-carboxyrnuconic-6-semialdchydc, can be diverted from complete oxidation, and used for the synthesis of NAD (see Niacin in Chapter 9). 

Figure 21 Mechanism for the synthesis of precorrin-3B from precorrin-3A. In nature there are at least two distinct enzymes that can catalyze the synthesis of the hydroxyl gamma lactone derivative of precorrin-3A. In Pseudomona denitrificans this reaction is catalyzed by CobG, which likely utilizes a bound nonheme iron to activate molecular oxygen. In R. capsulatus, this reaction is mediated by CobZ, which harnesses the oxygen-binding ability of a flavin.

Heme, the most abundant iron cofactor, can play diversified roles in the cell. These roles include not only the already-mentioned regulatory and signal transduction processes, but also electron transfer, oxygen binding and transport, and direct involvement in the oxygen metabolism. The first step of the heme biosynthetic pathway in mammalian cells is catalyzed by 5-aminolevulinic acid synthase (ALAS), which is considered a rate-limiting step in the production of heme. The rate of synthesis of erythroid ALAS is directly dependent on the cellular iron concentration. Ferreira reviews recent structural and site-directed mutagenesis studies on ALAS (Chapter 2), which, for example, have revealed that the homodimeric enzyme s active site is located at the subunit interface and contains catalytically essential residues from both subunits. 

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