Hydroxylation processes

Archelas A, J-D Fonmeron, R Fnrstoss, M Cesario, C Pascard (1988) Microbial transformations. 8. First example of a highly enantioselective microbiological hydroxylation process J Amer Chem Soc 53 1797-1799. 

Reinhold and Bruni studied the metabolism of 7,9-dideuterioellipticine (17) in rats and found that deuterium originally at position 9 was completely lost during the mammalian hydroxylation process (147). Proton and carbon-13 NMR and mass spectral analyses confirmed the complete elimination of deuterium at position 9, thus ruling out the occurrence of an NIH shift mechanism in the hydroxylation of ellipticine. An oxygen-insertion process was rationalized to account for the mechanism of aromatic hydroxylation in rats since this would not be expected to display the NIH shift but should demonstrate an isotope effect. It was... 

Hydroxylation of an alkene may be carried out using osmium tetroxide in an inert solvent (e.g. ether or dioxane), whereupon a cyclic osmate ester is formed. This undergoes hydrolytic cleavage under reducing conditions (e.g. aqueous sodium sulphite) to give the 1,2-diol resulting from a ds-hydroxylation process.71... 

Alternatively and more conveniently this ds-hydroxylation process can be effected using only catalytic amounts of osmium tetroxide together with hydrogen peroxide, which cleaves the first formed osmate ester to the diol and regenerates the osmium tetroxide. The reaction is carried out in t-butyl alcohol and is illustrated by the conversion of cyclohexene into ds-cyclohexane-l,2-diol (Expt 5.47). 

A 1,2-diol arising from a trans-hydroxylation process is formed from an alkene by way of an intermediate epoxide which is subjected to a ring-opening reaction and hydrolysis. The epoxides may be isolated when the alkene is reacted with perbenzoic add or m-chloroperbenzoic acid (Section 4.2.56, p. 457) in a solvent such as chloroform or dichloromethane the preparation of epoxides by this method and by other important procedures are discussed and illustrated... 

In the biosynthesis of haemanthamine (318) hydroxylation at the methylene at position 11, to the nitrogen atom, takes place late in the sequence once the 5,10b-ethanophenanthridine skeleton had been constructed from O-methylnorbelladine (102). The stereochemical course of the hydroxylation process has been studied independently by two groups. 

The production volume of hydrogen peroxide is in hundreds of thousands of tons. It is one of the most widespread and valuable products in modem chemistry. All over the world hydrogen peroxide is widely applied in epoxidation and hydroxylation processes, for example, in glycerol production from allyl alcohol or organic peroxides, which are polymerization and vulcanization initiators. 

The characteristics of this reaction were studied by Burstein and Kupfer (7) who showed that it followed the pattern of a typical mixed-function oxidase system. They showed that all the metabolizing activity occurred in the microsomal fraction and that oxygen and NADPH were required. Other agents such as SKF-525A (8-di-ethylaminoethyldiphenylpropyl acetate), Burstein and Kupfer (8), and DDT, Kupfer et al. (9), were reported to inhibit this hydroxylation process. 

A fermentation process was developed for the production of epothilone B, and the titer of epothilone B was increased by a continuous feed of sodium propionate during fermentation. The inclusion of XAD-16 resin during fermentation to adsorb epothilone B and to carry out volume reduction made the recovery of product very simple (Benigni et al., 2004). A microbial hydroxylation process was developed for the conversion of epothilone B (10) to epothilone F (11) by Amycolatopsis orientalis SC 15847. A bioconversion yield of 37-47 % was obtained when the process was scaled up to 100-250 L. Recently, epothilone B hydroxylase and the ferredoxin gene have been cloned and expressed in Streptomyces rimosus from Amycolatopsis orientalis SC 15847 by our colleagues in Bristol-Myers Squibb. Mutants and variants thereof this cloned enzyme has been used in the hydroxylation of epothilone B to epothilone F to obtain even higher yields of product (Basch et al, 2004). 

The irradiation of nitrophenols in the presence of nitrite and nitrous acid mainly results in hydroxylation processes upon reaction with OH, leading to the corresponding dihydroxynitrobenzenes [109]. The absorption spectra of nitrophenols, nitrite and nitrous acid overlap, thus irradiation also results in the direct excitation of nitrophenols, with possible photolysis. Accordingly, it is very likely that many of the minor intermediates detected in the cited sys-... 

Hydroxyl radical generated from hydrogen peroxide in the presence of iron(II) salts hydroxylates most aromatic centres, and indeed a phenol hydroxylation process based on this chemistry was operated for nearly a decade.471 The process ran at similar conversions to the acid-catalysed route mentioned above, however selectivity to dihydroxybenzenes was somewhat lower, and some resorcinol was formed along with catechol and hydroquinone. 

In enzymatic hydroxylation processes the entering oxygen atom is provided by gaseous oxygen (usually from the air), and not by water or any other oxygen-containing compound... 

In these cases no monohydroxylated products were isolated. Since N. corallina is normally a A -dehydrogenating microorganism, it has been proposed that A -compounds are intermediates in these hydroxylation processes. 

The first recorded 11/ -hydroxylation of a steroid was the transformation of 1 l-deoxy-17-hy-droxycorticosterone (1) into hydrocortisone (2) with Streptomyces fradiae205, albeit in very low yield. The first practical 11/J-hydroxylation processes were those using Curvularia lunala2 206 and Cunninghamella blakesleeana207-20R. The special strain, Curvularia lunata NRRL 2380, discovered via extensive screening operations, has continued to be important for the commercial production of hydrocortisone from 1. 

The relatively small capacity of the phenol hydroxylation process does not justify the development of alternatives to the use of commercial hydrogen peroxide. The direct synthesis of phenol, for which process integration might be crucial, would be a different matter. 

A rather novel biotransformation that can occur as part of an aromatic hydroxylation process has been called the NIH shift whereby a substituent such as bromo, chloro, and fluoro at the position of hydroxylation undergoes migration to the adjacent position. Relevant examples are relatively few but this may be due to the lack of rigorous identification of ring-hydroxylated metabolites. 

E. Guittet and S. JuliS, Synth. Commun., 1981, 11, 723. Recently the high transmission of stereochemistry in the 2,3-sigmatropic rearrangement of allyl sulfoxide systems has been used in an allylic hydroxylation process via an asymmetric ene reaction of N-sulfinylcarbamates J. K. Whitesell, J. F. Carpenter, H. K. Yaser and T. Machajewski, J. Am. Chem. Soc., 1990, 112, 7653. 

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