Co-Hydroxylation

Aikaliniry Bicarbonates (HCOd Carbonates (CO,) Hydroxyl (OH) as CaCO, Steam systems foaming and solid carry over Steel embrittlement (HCO,) and (CO,) Corrosion Distillation Demineralization I..ime and lime soda Dealkalization I lon exchange) Acid treatment liydrogcn zeolire... 

Although also iron-sulfur proteins, the rubredoxins do not generate H2S on acidification since in this case the thiol groups are contributed by cysteinyl residues in the polypeptide chain. The function of clostridial rubredoxin is as yet unknown in Pseudomonas sp. a similar protein catalyzes the co-hydroxylation of alkanes, a reaction requiring molecular O2. 

Although the biocompatibility and biodegradability of these materials were rapidly determined, the bioactivity of Si02-PCL hybrid materials was not studied until recently [99]. In order to provide bioactivity to Si02-PCL hybrid materials, Rhee prepared triethoxysilane end-capped poly(s-caprolactone) which was then cocondensed with tetraethyl orthosilicate and calcium nitrate via the sol-gel method. The Ca-containing PCL/silica hybrid so obtained showed in vitro bioactivity and biodegradability. The hybridization procedure between the a,co-hydroxyl PCL and silica phases was proposed to be as follows ... 

End-capping of both ends of a,co-hydroxyl PCL with 3-isocyanatopropyl triethoxysilane (IPTS). 

Fig. 12.9 Scheme of the formation of a hybrid between a,co-hydroxyl PCL and silica phases. 

Macrolactonization of co-hydroxyl acids using a combination of DCC, DMAP and DMAP-HCl. 

Scheme 23.18 a De novo biosynthesis of coconut-like 6-pentyl-a-pyrone by Trichoderma sp. b Production of macrocyclic musk-like lactones by a combination of microbial co-hydroxylations and co-l-hydroxylations and subsequent chemical conversion steps, c Production of macrocyclic musk fragrances initiated by terminal oxidation of hydrocarbons with Candida tropicalis... 

In the same year the biotransformation of these monoterpenes by B. cinerea in model solutions was described by another group [41]. Although the major metabolites found were co-hydroxylation compounds, it is important to note that these authors only identified the -isomers in the extracts and that some new compounds were detected that were not described by the previous group, Fig. (9). Geraniol (20) was mainly transformed to (2 ,5 )-3,7-dimethyl-2,5-octadiene-l,7-diol (53), ( )-3,7-dimethyl-2,7-octadiene-l,6-diol (54) and (2 ,6 )-2,6-dimethyl-2,6-octadiene-1,8-diol (43), nerol (14) to (2Z,5 )-3,7-dimethyl-2,5-octadiene-1,7-diol (55), (Z)-3,7-dimethyl-2,7-octadiene-l,6-diol (56), and (2E,6Z) 2,6-dimethyl-2,6-octadiene-1,8-diol (47). Furthermore a cyclisation product (57) was formed which was not previously described. Finally citronellol (4) was converted to trans- (60) and cw-rose oxide (61) (a cyclisation product not identified by the other group), ( )-3,7-dimethyl-5-octene-l,7-diol (58), 3,7-dimethyl-7-octene-l,6-diol (59) and ( )-2,6-dimethyl-2-octene-1,8-diol (34). 

As mentioned before (2.1.1) Arfmann et al. [133] studied the co-hydroxylation of the sesquiterpenes nerolidol and famesol and the related compounds neryl- and geranylacetone. This was done because co-hydroxylated sesquiterpenes are important intermediates in the synthesis of industrially used fragrances and flavours. Aspergillus niger ATCC 9142 and Rhodococcus rubropertinctus DSM 43197 were unable to hydroxylate nerylacetone or its -isomer geranylacetone, at the co-position of the molecule. Incubation of nerylacetone with Mucor circinelloides CBS 27749 for 25 hr resulted in seven transformation products, including one co-hydroxylation compound, in 3% yield [140]. 

The bioconversion of geranylacetone with Aspergillus niger yielded the co-hydroxylation product 11-hydroxygeranylacetone and the vicinal diol (S)-(-)-9,10-dihydroxygeranylacetone as in the case of nerolidol and famesol [135]. The same reactions were noticed in the bioconversion of geranylacetol. 

Pseudomonas oleovorans contains P. oleovorans monooxygenase (POM), which is a typical co-hydroxylase for hydroxylation of the terminal methyl of alkanes as well as epoxidation of terminal olefins. The co-hydroxylation system of P. oleovorans was reconstituted from purified components, POM, rubredoxin, and a flavoprotein reductase [122], In the presence of NADH and oxygen, it oxidizes a wide range of aliphatic methyl alkyl sulfides. Enantioselectivities are very much dependent of the length of the alkyl chain of Me-S(0)-R, as exemplified by the following results ... 

Macrolactonization. The usually difficult lactonization to 11-membered pyrroli-zidine dilactones can be achieved by use of a trimethylsilylethyl ester (8, 510-511) and activation of the co-hydroxyl group by mesylation. Thus treatment of 1 with (C4H9)4N+F in acetonitrile at 30° liberates the carboxyl group with spontaneous cyclization to the diastereomer 2, the methoxymethyl ether of c//-crispatine.4... 

Disposition in the Body. About 10% of a dose is concentrated in the brain within 1 minute of an intravenous injection and it is then rapidly distributed throughout the body, eventually accumulating in body fat about 50% of a dose accumulates in this way after 30 to 90 minutes. The very short action of thiopentone is due to the brief a-phase half-life and the redistribution of the drug from the brain to other fatty tissues. Metabolic reactions include co-hydroxylation, further oxidation and, to a lesser extent, desulphuration to pentobarbitone. Less than 1% of a dose is excreted in the urine as unchanged drug. 5-(3-Carboxy-... 

The one-step synthesis of a,co-hydroxylated dimers of 1,3-dienes or maleic acid uses alcohol (t-butanol, n-butanol, isopropanol, ethanol)/H202/FeS04 as a catalyst 72 73>. Organic hydroxylated radicals are generated from the alcohol by hydrogen abstraction ... 

Bush, J.W. Co. Hydroxylation of Alkenyl Substituted Aromatr Compounds 1968 GB 1,119,612... 

Lu AYH, Coon MJ. 1968. Role of heme-protein P-450 in fatty acid co—hydroxylation in a soluble enzyme system from liver microsomes. J. Biol. Chem. 243 1331-32... 

Lu AYH, Junk KW, Coon MJ. 1969. Resolution of the cytochome P-450 containing co—hydroxylation system of liver microsomes into three components. J. Biol. Chem. 244 3714-21... 

The degradation of alkanoic acids by P-oxidation has been noted parenthetically above, but alternative pathways may occur. For example, the metabolism of hexanoic acid by strains of Pseudomonas sp. may take place by co-oxidation with subsequent formation of succinate and 2-tetrahydrofurany-lacetate as a terminal metabolite (Kunz and Weimer 1983). In a strain of Cory neb acterium sp., the specificities of the relevant catabolic enzymes are consistent with the production of dodecanedioic acid by co-oxidation of dode-cane but not of hexadecanedioic acid from hexadecane (Broadway et al. 1993). Hydroxylation at subterminal (co-1, co-2, and co-3) positions of carboxylic acids with chain lengths of 12 to 18—and less readily of the corresponding alcohols, but not the carboxylic acids or the alkanes—has been observed (Miura and Fulco 1975) for a soluble enzyme system from a strain of Bacillus megaterium. Whereas in this organism co-2 hydroxylation is carried out by a soluble cytochrome P-450 BM 3 (Narhi and Fulco 1987), co-hydroxylation in P. oleovorans that carries the OCT plasmid is mediated by a three-component hydroxylase that behaves like a cytoplasmic membrane protein (Ruettinger et al. 1974 Kok et al. 1989). 

Aromatic methyl and ethyl ethers may be metabolized to give the phenol and corresponding aldehyde (figure 4,16), as illustrated by the de-ethylation of phenacetin (figure 5,20). Ethers with longer alkyl chains are less readily (Udealkylated, the preferred route being co- -hydroxylation. 

A rubredoxin-type protein of about 19,000 dalton, which binds up to two iron atoms per molecule (237, 238), has been found as a component of the co-hydroxylation system of the aerobic bacterium Pseudomonas oleo-vorans (213, 214). Its primary structure suggests two sequences homologous with that of rubredoxin from anaerobic bacteria (Fig. 11) (239). On this basis the authors have speculated on the possibility of an evolutionary divergence from a common ancestor for all these organisms so that the heavier type rubredoxin may have resulted by gene duplication. In the process, the specificity of the enzyme was so affected that 1-Fe rubredoxins cannot substitute for the 2-Fe protein in the co-hydroxylation reaction. 

The enzymatic system involved in hydroxylation reactions of long-chain alkanes had been previously studied by Coon and coworkers, who isolated an enzyme system from P. oleovorans that catalyzes co-hydroxylation of alkenes and fatty acids120, 106-nsl. This was resolved into three protein components rubredoxin (an iron-sulfur protein of molecular weight 19 000), an NADH-rubredoxin reductase (a flavoprotein of molecular weight 55 000) and an co-hydroxylase (characterized as being a non-heme iron protein, with one iron atom and one cysteine per polypeptide... 

A similar result was obtained later on using the 1-octene substrate itself as the organic phase (20% v/v), leading to comparable results (70% ee) 11S. Interestingly it also has been shown in the course of this work that, when n-hexadecane (which is not metabolized by the cells) is used as a solvent, racemic epoxide is enantiose-lectively degraded by the co-hydroxylation enzymatic system of P. oleovorans, leading to an enrichment in (S)-l,2-epoxyoctane. 

While microsomal co-hydroxylation is not believed to represent a major pathway for hepatic fatty acid catabolism under normal physiological conditions, this highly inducible pathway may become important under certain conditions such as fasting or exposure to peroxisome proliferators. In addition to FA catabolism, the cytochrome P450 4As (CYP4As) involved in this pathway catabolize leukotrienes and prostanoids and also generate bioactive molecules from arachidonic acid co-hydroxylation. 

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