- Isolation and partial synthesis of a new metabolite of medroxyprogesterone acetate
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3α-Hydroxy-17-acetoxy-6α-methyl-5β-pregnan-20-one (IIIa) has been isolated from urine of patients receiving medroxyprogesterone acetate (MPA). It was characterized by partial synthesis from MPA by catalytic reduction with palladium-charcoal to 17-acetoxy-6α-methyl-5β-pregnan-3,20-dione (IV) and reduction of the latter with sodum borohydride. The isolation of 6β,17,21-trihydroxy-6α-methyl-pregn-4-ene-3,20-dione (IIc) is reported for the first time. The 17- and 21-monoacetates of this compound have been isolated and characterized earlier by other investigators. 7α-3H-Medroxyprogesterone acetate was administered to 4 subjects by intravenous and intramuscular injections and by mouth. The ring A saturated metabolite IIIa was excreted in 0.1% to 4.0% of the administered dose; the highest excretion was after the intravenous dose and lowest after oral ingestion. 6β,17,21-Trihydroxy-6α-methylpregn-4-ene-3,20-dione (IIc) and its 17- and 21-monoacetates were excreted in about 5% of the doses in all subjects. No increase in 6β-hydroxylation was observed in the patient treated with o,p'-DDD, 2,2-bis (2-chlorophenyl, 4'-chlorophenyl)-1,1-dichloroethane.
- Fukushima,Levin,Liang,Smulowitz
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- Synthesis of Ring-A and -B Substituted 17α-Acetoxypregnan-20-one Derivatives with Potential Activity on the Digitalis Receptor in Cardiac Muscle
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The synthesis of C-6 substituted (methyl, hydroxy, acetoxy, methoxy, ethoxy, methoxycarbonyloxy, ethoxycarbonyloxy, fluoro, chloro, bromo) 5α,5β,C-4 unsaturated and C-4,6 unsaturated derivatives of 17α-acetoxypregn-4-ene-3,20-dione (17α-acetoxyprogesterone) are reported.A convenient synthesis of 6α-hydroxy derivatives by selective reduction of the 4-ene-3,6-dione system is described as is the formation of 6α-alkoxycarbonyl derivatives.Synthesis of a 5α-hydroxy-6-ketone via 5β,6β-epoxide with N-bromosuccinimide is reported.A new preparation of 3α-hydroxy-5α-derivatives from the 4-en-3-one group has been carried out. (1)H n.m.r. are recorded.These compounds were synthesized to test for ouabain displacement activity an the digitalis receptor in cardiac muscle.
- Templeton, John F.,Kumar, V. P. Sashi,Kim, Ryungsoon S.,LaBella, Frank S.
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p. 1361 - 1368
(2007/10/02)
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