Testosterone oxidation system

The microreactor could also serve as a tool for quick scale-up of Swern-Moffatt oxidations. The scalability and reliability of the microreactor were tested by running the system for several hours. For testosterone, the system was operated for 1.5 h, resulting in an 4-androstene-3,17-dione production rate of 64g/h. 

Mooradian (1993) has studied the antioxidant properties of 14 steroids in a non-membranous system in which the fluorescence of the protein phycoerythrin was measured in the presence of a lipid peroxyl radical generator (ABAP). Oxidation of the protein produces a fluorescent species. Quenching of fluorescence by a test compound indicates antioxidant activity. Oestrone, testosterone, progesterone, androstenedione, dehydroepian-drosterone, cortisol, tetrahydrocortisone, deoxycorti-... 

As previously mentioned, degradable microspheres have gained attention as promising delivery vehicles for steroids in postmenopausal therapy. Copolymers of CL and d,l-LA were used to prepare microspheres for prolonged release of progesterone and [5-estradiol. The system offered a constant release for up to 40 days in vitro and 70 days in vivo [226]. Similarly, PCL copolymers have been considered useful for androgen replacement therapy in the treatment of aging men with a testosterone deficiency. Micelles of PCL-block-poly(ethylene oxide) released dihydrotestosterone in a controlled fashion over 30 days. The biocompatibility was confirmed in vitro in a HeLa cell culture [227]. 

Amongst other less successful jqiplicadons, howevo-, are the oxidations of some steroidal systems such as testosterone, which afforded AAandrosterone-3,17-dione in only 34% yield and 1 la-l droxypro-gesterone, in which the equatorial hydroxy group was oxidized to affod a poor yield of 11-oxoproges-terone (13%). ... 

Carbon monoxide inhibited the 6/3-. la-, and 16a-hydroxylation of testosterone by rat liver microsomes to different extents. A C0/02 ratio of 0.5 inhibited the la-, 6/i-, and 16a-hydroxylation reactions by 14%, 25%, and 36%, respectively, and the ratio of C0/02 needed for 50% inhibition of testosterone hydroxylation in the 16a-, 6/3-, and 7a-positions was 0.93, 1.54, and 2.36, respectively (36,48). Studies on the photochemical action spectrum revealed that CO inhibition of the three hydroxylation reactions was maximally reversed by monochromatic light at 450 nm, but there were differences in the shape of the photochemical reactivation spectra for the 6/3-, la-, and 16a-hydroxylation reactions (36,48). The data from our laboratory summarized above and at the First International Symposium on Microsomes and Drug Oxidation in 1968 pointed to multiple cytochromes P450 with different catalytic activities that were under separate regulatory control (36,45,46), and we indicated that the actual number of cytochromes that participate in the multiple hydroxylation reactions must await the solubilization and purification of the microsomal system (36). The use of different inducers of liver microsomal monooxygenases caused selective increases in the concentration of specific cytochromes P450 in fiver microsomes that greatly facilitated the isolation and purification of these hemoproteins. 

The chemical transformations of testosterone (L) by the liver and the enzyme systems involved have been studied extensively. In rabbit liver slices, the 17 8-hydroxyl group is oxidized to the 17-ketone to give androstene-3,17-dione (LV).i That this transformation takes place is further evidence for the first step in the metabolic scheme outlined in Fig. 10. From the same incubation 17a-hydroxy-A -androstene-3-one (LXX, cfs -testosterone), as well as testosterone, was obtained. Furthermore, incubation of 17a-hydroxy-A -androstene-3-one (LXX) afforded A -androstene-3,17-dione (LV),i and all three products were isolated after incubation of A -androstene-3,17-dione with liver. These results demonstrate that the 17-ketone can be reduced to either a 17a- or 17j8-hydroxyl group and both can be oxidized back to the ketone. Therefore,... 

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