3 ,4 -Dihydroxylated metabolite

Bromobiphenyl produced a major metabolite (4% of the dose) identified as either 3-bromo-4-biphenylol or 5-bromo-2-biphenylol a minor dihydroxylated metabolite was also detected. 4-Bromobiphenyl yielded two metabolites 4 -bromo-4-biphenylol (2% of the dose) and 4 -bromo-3,4-biphenyldiol (1.5% of the dose). Experiments witli tritiated 4-bromobiphenyl suggest that the metabolism of this congener involves the formation of an arene oxide. 

Henry HL and Norman AW (1978) Vitamin D two dihydroxylated metabolites are required for normal chicken egg hatchability. Science 201, 835-7. 

Sottani C, Minoia C, Colombo A, Zucchetti M, DTncalci M, Fanelli R (1997) Structural Characterization of Mono- and Dihydroxylated Metabolites of Paclitaxel in Rat Bile Using Liquid Chromatography/Ion Spray Tandem Mass Spectrometry. Rapid Comm in Mass Spec 11 1025... 

Resolution of vitamin D metabolites and application to biological materials. The amounts of mono- and dihydroxylated metabolites in human plasma/serum are too low to permit TLC with in... 

Metabolite profiling of [ H]-24 done in rat hepatocytes indicated three monohy-droxylated and multiple dihydroxylated metabolites based on mass spectral characterization [11]. Quantities of metabolites needed for NMR characterization were initially generated by incubation of parent compound with pregnenolone 16a-carbonitrile (PCN)-induced rat liver microsomes. NMR studies indicated that the major metabolite was 8-p-OH compound 25 and the minor metabolites were 7a- and 7p-hydroxy derivatives 26 and 27, respectively (Figure 19.8). In cynomolgus monkeys also, a similar pattern of metabolites was seen after oral administration of the compound in plasma samples drawn from experimental animals at 6 h and 24 h time points. 

Clearly, though solvents in the second class are desirable to minimize contamination of vitamin D extract, they pose problems in that they tend to provide efficient extraction for one particular metabolite or group of metabolites (e.g., the dihydroxylated metabolites) and poorly extract those of a different polarity. When simultaneous analysis of several vitamin D metabolites with a wide range of polarities is required, a total lipid extraction (83) may be necessary. The high efficiency of the Bligh and Dyer technique (83) for total lipid extraction (i.e., methanol chloroform 2 1, v/v) is probably due to the formation of a monophasic dispersion of sample in extracting solvent, followed by return to the classic two-phase system by addition of extra chloroform and saturated KCl. All hydroxylated nonacidic vitamin D metabolites can be extracted quantitatively by this technique. 

Sesquiterpene lactones with an eudesmane-6a-olide structure are abundant in nature and the biotransformations of some of them, such as a-santonin 87, have been extensively investigated [94]. Beside reduction products, using A. niger MEL 5024, several monohy-droxylated metabolites at positions C-8, C-11, and C-13 have recently been isolated [119], while a Pseudomonas strain (ATCC 43388), incubated with a-santonin in the presence of an ATPase inhibitor, accumulated a 4,5-dihydroxylated metabolite (88) [120]. 

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 . 

These findings were also in contrast to the results they obtained carrying out the bioconversion of nerolidol with Aspergillus niger [135,136]. In this case, the two main metabolites identified were 12-hydroxynerolidol (159) and 10,11-dihydroxynerolidol (160). The same reactions were noticed when dihydronerolidol was used as substrate co-methyl hydroxylation and dihydroxylation of the remote double bond. 

Versatile epoxyquinol intermediates were conveniently accessed via metabolites derived from the enzymatic dihydroxylation of bromobenzene [172]. The chemoen-zymatic approach led to shortened total syntheses of several epoxyquinols derived... 

The vitamin D metabolites (l,25(OH)2D3 and 24,25(OH)2D3) are also known to exert an effect upon cartilage [33]. Receptors for both dihydroxylated vitamin D metabolites have been apparently found in this tissue, and they both can stimulate the uptake of 35S04 into proteoglycans. 

---