Alfadolon

Alphadolone Chemische Eigenschaften,Einsatz,Produktion Methoden

• Originator

  Alphadolone ,RiboTargets Ltd.

• Verwenden

  Alphadolone or Alfadolone (INN) is a neuroactive steroid with hypnotic effects. Alphadolone is one of the components of Althesin.

• Manufacturing Process

  A solution of 3β-acetoxy-5α-pregn-16-ene-11,20-dione (Chamberlin et al., J.Amer. Chem Soc., 1951, 73, 2396) (25.7 g) in dioxan (Analar, 500 ml) was treated with potassium hydroxide (10 g) and water 250 ml and the mixture allowed to stand at room temperature for 1 h. After a further 1 h at 40°C the mixture was diluted with water and the product filtered off. The crude material was dissolved in chloroform and filtered through a column of grade III neutral alumina (100 g). The material obtained was crystallized from acetonepetroleum to give pure 3β-hydroxy-5α-pregn-16-ene-11,20-dione (17.65 g, 77.5%) as small plates, melting point 217.5°C.
  A solution of 3β-hydroxy-5α-pregn-16-ene-11,20-dione (39.6 g) in dry pyridine (165 ml) was treated with toluene-p-sulfonyl chloride (43.9 g) to give the toluene sulfonate (56.7 g), melting point 147-151°C. A portion (10.7 g) of this material was crystallized from ethyl acetate-petroleum to give the pure 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (9.2 g) as plates, melting point 154°-155°C.
  2 Methods of producing of 3α-hydroxy-5α-pregn-16-ene-11,20-dione from 3β- toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione:
  1. A solution of 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (19.1 g) in N,N-dimethylformamide (160 ml) and water (16.0 ml) was treated with potassium acetate (29.2 g) and the mixture heated at 115°C for 2.5 h. The solvents were removed in vacuo and residue partitioned between chloroform and water. The chloroform extract was washed with water, dried and evaporated. The residue was taken up in methanol (500 ml) and solution flushed with nitrogen. Potassium hydroxide (17 g) in water (70 ml) was added and the solution refluxed for 1 h. Glacial acetic acid was added to bring the pH to about 6 and most of the methanol evaporated in vacuo. Dilution with water gave a gummy precipitate which was extracted into chloroform to give the crude product. This material was extracted with ether and the residue boiled with benzene. The insoluble material was crystallized from chloroformpetroleum to give 3α-hydroxy-5α-pregn-16-ene-11,20-dione (3.28 g) as large prisms, melting point 243°-244°C.
  2. A mixture of the 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (60 g; 0.124 mole) in N,N-dimethylformamide (350 ml) and potassium acetate (92 g, 0.94 mole) in water (935 ml) was stirred at 115°C for 4 h. The brown solution was cooled and most of the N,N-dimethylformamide removed by evaporation at 50°C and 4 mm to give a brown solid mass. Another run with to sylate (58 g, 0.12 mole), potassium acetate (90 g, 0.91 mole), N,Ndimethylformamide (350 ml) and water (35 ml) was carried out as described above. The combined aqueous fractions were extracted with chloroform (3 x 100 ml) and dried over magnesium sulfate. The chloroform was removed in vacuo and residual N,N-dimethylformamide was evaporated at 50°C and 4 mm to give the crude 3α-acetate-5α-pregn-16-ene-11,20-dione (92 g) as a brown solid.
  A solution of 3α-acetate-5α-pregn-16-ene-11,20-dione (92 g) in dioxin (1000 ml) was mixed with a solution of potassium hydroxide (45 g, 0.8 mole) in water (500 ml) to give a two-phase system. A homogeneous solution was obtained by the addition of dioxin (440 ml) and water (625 ml). Nitrogen was bubbled through the solution which was heated at 50°C for 2 h. The port colored solution was treated with glacial acetic acid (40 ml) to bring the pH about 7 and two thirds of the solvent was removed by distillation in vacuo (water pump). Water (3 L) was added to the resultant mixture (which had already begun to crystallize) and the precipitated solid was filtered off, washed with water and dried over phosphorus pentoxide to give the crude 3α- hydroxy-5α-pregn-16-ene-11,20-dione (73.9 g).
  Producing of 3α,21-dihydroxy-5α-pregnane-11,20-dione from 3α-hydroxy-5α- pregn-16-ene-11,20-dione: A solution of 3α-hydroxy-5α-pregn-16-ene-11,20-dione (200 mg) in freshly distilled tetrahydrofuran

• Therapeutic Function

  Anesthetic

• Clinical Use

  Althesin is an effective intravenous anesthetic for short surgical procedures or for induction of lengthy anesthesia . Doses of 0.050 – 0.075mLper kg of body weight produce anesthesia in adults for 5 – 20 min and analgesia to surgical stimuli for 2 – 5 min. Althesin causes cardiodepressive side effects. Although it is used in countries in which French pharmaceuticals dominate, it is hardly used in Germany.

Alphadolone Upstream-Materialien And Downstream Produkte

Alfadolon Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(32)Suppliers

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