Monohydroxylation

Oxidation of hexa/luorobenzene to peniafluorophenol is accomplished by heatmg with concentrated hydrogen peroxide [46] (equation 39) Under these conditions, pentafluorobiphenyl is monohydroxylated on the nonfluonnated nng [46] (equation 40)... 

The RICs for m/z 614, indicating unchanged Indinavir, and m/z 630 and 646, i.e. those expected from its mono- and dihydroxymetabolites, are shown in Figure 5.41. This allows the presence of three monohydroxylated and one dihy-droxylated metabolite to be demonstrated the other responses observed were shown by the authors not to be associated with the drug. The MS-MS spectrum of the molecular species of the dihydroxylated compound did not allow its structure to be determined but those from the molecular species from the monohydroxylated compounds allowed the structures shown in Figure 5.42 to be proposed and these correlate well with the findings from other laboratories . 

Grund E, C Knorr, R Eichenlaub (1990) Catabolism of benzoate and monohydroxylated benzoates by Amyco-latopsis and Streptomyces spp. Appl Environ Microbiol 56 1459-1464. 

A cytochrome P450 has been purified from Saccharomyces cerevisiae that has benzo[a]pyrene hydroxylase activity (King et al. 1984), and metabolizes benzo[fl]pyrene to 3- and 9-hydroxybenzo[fl]pyrene and benzo[fl]pyrene-7,8-dihydrodiol (Wiseman and Woods 1979). The transformation of PAHs by Candida Upolytica produced predominantly monohydroxyl-ated products naphth-l-ol from naphthalene, 4-hydroxybiphenyl from biphenyl and 3- and 9-hydroxybenzo[fl]pyrene from benzo[fl]pyrene (Cerniglia and Crow 1981). The transformation of phenanthrene was demonstrated in a number of yeasts isolated from littoral sediments and of these, Trichosporumpenicillatum was the most active. In contrast, biotransformation of benz[fl]anthracene by Candida krusei and Rhodotorula minuta was much slower (MacGillivray and Shiaris 1993). 

Spain JC, GJ Zylstra, CK Blake, DT Gibson (1989) Monohydroxylation of phenol and 2,5-dichlorophenol by toluene dioxygenase in Pseudomonas putida FI. Appl Environ Microbiol 55 2648-2652. 

Ciprofloxacin G. striatum Erlenmeyer flasks containing 10 mg L 1 33% after 13 weeks. Monohydroxylated congeners [30]... 

A good example of metabolite screening as part of a discovery PK study was reported by Tiller and Romanyshyn.123 They described a dog PK study in which a monohydroxylated metabolite was found at much higher levels than the dosed NCE it was active and fit the pharmacodynamic (PD) profile better than the dosed NCE. 

The selective monohydroxylation of heterocyclic compounds such as piperidine derivatives1741 and the 7-lactam (19)[751 have been studied. It is also been shown that hydroxylation of phenylcyclohexane can be effected using cytochrome P450 and the regioselectivity of hydroxylation can be altered by site-directed mutagenesis of the enzyme1761. 

Solvates of the monohydroxylic alcohols have been extensively studied. The expected pattern of more solvent molecules per chloride molecule is reported for the lanthanide and yttrium trichlorides. For scandium trichloride, the existence of ScCl3-2EtOH and ScCl3-2C6H13OH compares unexpectedly with the tris-alcoholates reported for the n-C6... 

Sources of Solubility Data for Trichlorides in Monohydroxylic Alcohols... 

Hydroxyl group effects were determined by Djerassi and co-workers (110) (cf. Sect. HI) by analysis of 31 monohydroxylated steroids. The following relationships were given ... 

The metabolism of chlorexolone to three monohydroxylated derivatives (all apparently substituted in the cyclohexane ring) in both dog and man has been reported [334]. No storage in body tissues could be detected and elimination via the kidney appeared to follow oxidation to the polar metabolites (no unchanged drug could be recovered from urine). These findings contrast with those relating to thiazides which often appear unchanged in urine. 

Nature often uses two pathways to produce oxygenated molecules. One is oxidative fictionalization of substrates through enzymatic hydration, monohydroxylation, dihydroxylation or epoxidation. Alternatively, oxygenated compounds can be generated by C—C formation catalyzed by aldolase, transketolase, oxynitrilase and related enzymes, where chiral centers are created simultaneously without an overall change in oxidation states [78]. 

NADP(H) [83, 84]. In addition to dioxygenation, non-heme iron oxygenases can perform monohydroxylation as in the synthesis of L-DOPA from L-tyrosine in mammalian species [85]. 

Besides a variety of other methods, phenols can be prepared by metal-catalyzed oxidation of aromatic compounds with hydrogen peroxide. Often, however, the selectivity of this reaction is rather poor since phenol is more reactive toward oxidation than benzene itself, and substantial overoxidation occurs. In 1990/91 Kumar and coworkers reported on the hydroxylation of some aromatic compounds using titanium silicate TS-2 as catalyst and hydrogen peroxide as oxygen donor (equation 72) . Conversions ranged from 54% to 81% with substituted aromatic compounds being mainly transformed into the ortho-and para-products. With benzene as substrate, phenol as the monohydroxylated product... 

Inhibition of the activities of F3 H or F3, 5 H should enable production of pelargonidin-based anthocyanins in species that lack them. Dendranthema is one candidate for such an approach.Of course, the subsequent enzymes would need to be able to use the substrates with only monohydroxylation of the B-ring, and in particular, DFR specificity would be a consideration for some species (e.g., Cymbidiuni). Reports of transgenic plants demonstrating this approach have yet to be published. 

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