L,4-Androstadiene-3,17-dione

Typically, sterol concentrations of 3 to 4 g l 1 are used and incubation times of about lOOh. Yields are dependent upon the species and substrates used. Some data relating to the yields of l,4-androstadiene-3,17-dione from various sterols and steroids using cultures of Arthrobacter simplex are reported in Table 9.3. 

The data shown in Table 9.3 indicate that highest yields of l,4-androstadiene-3,17-dione are obtained using lithocholic add as substrate. However, dtis substrate is not necessarily the one of choice for the commerdal production of l,4-androstadiene-3,17-dione using A. simplex, list factors that could deteimine the choice of substrate. 

The strains described in Table 9.4 are all of commerdal value since they produce compounds which are either pharmacologically active or can be converted to pharmacologically important compounds. For example, the production of l,4-androstadiene-3,17-dione from -sitosterol provides material which can be readily converted to estrone, while 4-androstene-3,17-dione can be converted to testosterone. 

Biotransformation as opposed to biodegradation may in fact be favored by limited oxygen concentration a good example is provided by the synthesis of 7a,12 3-dihydroxy-l,4-androstadien-3,17-dione from cholic acid by a strain of Pseudomonas sp. (Smith and Park 1984), in which oxygen limitation restricts the rate of C-9a hydroxylation that precedes degradation. 

Further work on the 7a-(4 -aminophenyl)thioandrostenedione (61, 7-APTA) was undertaken. The synthesis of an unsaturated derivative of (61) has resulted in the conversion of a reversible competitive inhibitor of AR into an enzyme-activated irreversible inhibitor. 7a-(4 -Aminophenyl)thio-l,4-androstadiene-3,17-dione (62, 7-APTADD) has an apparent Ki value of 9.9 + 1.0 nM (.Sfn, for androstenedione of 52.5 + 5.9 nM) and demonstrated rapid... 

The reduction of l,4-androstadiene-3,17-dione (AAD) as an industrial route to estradione using supercritical tetralin as both the solvent and the hydrogen donor Was investigated at Schering AG in cooperation with the University of Gottingen [177,178]. The reaction kinetics were studied at between 350-600 °C and 50-300 bar. A pilot plant with a possible throughput of up to 30 L h was studied successfully over 1 year with continuous processes run up to 4 days at 575 °C and pressures up to 100 bar at contact times of less than 1 s. 

Figure 12 Screening of a steroid library, (a) An imprinted polymer prepared for lla-hydro-xyprogesterone. Mobile phase dichloromethane (DCM) - 0.1% acetic acid v/v, Flux 0.5mL/min. (b) An imprinted polymer prepared for lla-hydroxyprogesterone. Gradient elution, 0-25 min, DCM 0.1% acetic acid v/v 25-30 min, DCM 0.1-5% acetic acid v/v 30-40 min, DCM 5% acetic acid v/v 40-45 min, DCM 5-0.1% acetic acid v/v. Flux 0.5mL/min. (c) A control polymer prepared in the absence of template molecule. Isocratic elution, DCM 0.1% acetic acid v/v. Flux 0.5mL/min. Sample component. (1) lla-hydroxyprogesterone, (2) lla-hydroxyprogesterone, (3) 17a-hydroxyprogesterone, (4) progesterone, (5) 4-androsten-3,17-dione, (6) l,4-androstadiene-3,17-dione, (7) corticosterone, (8) cortexone, (9) 11-deoxy-cortisol, (10) cortisone, (11) cortisone-21-acetate, (12) cortisol-21-acetate. Reproduced from Ref. 58, with permission.

Dehydrogenation at the 4-position was first described by Vischer and Wettstein (V-1056) with the conversion of 5a-androstane-3,17-dione and related species into l,4-androstadiene-3,17-dione by Fusarium solani. This class of transformation has... 

Japanese Patent 30915 (1964) Derwent Abstr. 19, 293). Degradation of cholesterol, sitosterol, or stigmasterol by Corynebacterium simplex and other known 1-dehydrogenating species, in the presence of agents which chelate copper or iron, to give 4-androstene 3,17-dione, l,4-androstadiene-3,17-dione, and other products. 

Henderson D, Norbisrath G, Kerb U (1986) 1-Meth-yl-l,4-androstadiene-3,17-dione (SH 489) characterization of an irreversible inhibitor of estrogen biosynthesis. J Steroid Bioehem 24 303 306... 

Isolation of l,4-Androstadiene-3,17-dione from Urine of an Epileptic Boy J. Steroid Biochem. 5(3) 269-272 (1974) CA 81 132404a... 

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