Transformations of Steroids by Cell-free Preparations of Penicillium lilacinum NRRL 895. III. Metabolism of Progesterone during Esterase Inhibition with Clomiphene Citrate.

Baeyer−Villiger Monooxygenases: More Than Just Green Chemistry

“…Large scale experiments with up to 30 L fungal cultures were conducted and confirmed that the metabolic degradation of steroids by fungal strains proceeds as follows: progesterone ( 8 ) to progesterone acetate ( 11 ) to testosterone ( 9 ) to androst-4-ene-3,7-dione ( 12 ), and finally to testolactone ( 7 ) (Figure ) . Experiments by Rakhit and Singh with 17α-deuteroprogesterone as starting material and extensive studies by Carlström confirmed the previously assumed pathway and mechanism of the microbial degradation of the side chain of steroids and D-ring lactonization . These initial research efforts were mainly driven by the potential commercial value of chemoenzymatic routes to valuable steroidal drugs such as cortisone or estrone, but instead of the aspired C-11 hydroxylation, research teams identified multiple oxidative changes on the D-ring as described above.…”

Metabolism of 17-hydroxyprogesterone by a Bacillus species

“…In the microbial degradation of the progesterone side chain, molecular oxygen is directly inserted into the C-I 7-C-20 bond to give testosterone acetate (Nakano et al, 1968), which is hydrolysed to testosterone and subsequently oxidized to (II). The pathway of formation of the side-chain-cleavage metabolites has been rationalized in the light of the non-enzymic Baeyer-Villiger type of oxidation of ketones to esters or lactones by peracids (Rahim & Sih, 1966;Miller, 1972;Carlstrom, 1973). The structure and mechanism of formation of the metabolites of (I) are shown in Scheme 1.…”

Effect of Clomiphene Citrate on Testicular Steroid Metabolism in Man

“…50 pg each of progesterone, 17a-hydroxyprogesterone, 20a-hydroxy-4-pregnen-3-one, 1 7n,20a-dihydroxy-4-pregnen-3-one, 4-androstene-3,l'i-dione and testosterone were added as carriers and the steroids were extracted with chloroform. T h e reaction mixture was analyzed by thin layer cromatography and liquid scintillation counting before and after acetylation as previously described (Carlstrom et al 1973(Carlstrom et al , 1974a(Carlstrom et al , 1974b. The quantitatively important steroids (progesterone, I 7~-hydroxyprogesterone, 20a-hydroxy-4pregnen-3-one and 17a20a-dihydroxy-4-pregnen-3-one) were identified by chromatographic mobility before and after acetylation, by 3H/I4C-ratio and by crystallization to constant specific activity as described previously (Carlstriim et al 1974a,b).…”