Activator III

To a solution of 0.5 g of lithium aluminum hydride in 35 ml of ether is added 0.2 g of the A -cyanoaziridine. The mixture is heated at reflux temperature for 3.5 hr, cooled, and treated with excess saturated sodium sulfate in water. Filtration and evaporation of the ethereal filtrate gives 0.18 g of a glass which is chromatographed on 10 g of basic alumina (activity III). The benzene-petroleum ether (1 3) eluate gives 0.12 g of 2a,3a-imino-5a-choles-tane, mp 117.5-118.5°, after crystallization from methanol. 

A solution of 6.3 g (0.9 moles) ethoxyacetylene in 50 ml ether is added dropwise during 30 min to a Grignard reagent prepared from 2.18 g (90 mg-atoms) magnesium and 9.81 g (90 mmoles) ethyl bromide. The reaction mixture is stirred for 1 hr at room temperature and then a solution of 3 g (9 mmoles) 3) -acetoxyandrost-5-en-I7-one in 50 ml dry ether is added dropwise. The mixture is refluxed for 1 hr and after cooling to 0° poured into 100 ml of an aqueous ammonium chloride solution. The aqueous solution is extracted with ether, and the organic extract is washed with ammonium chloride solution and water, dried, and evaporated. The residue is chromatographed on 130 g alumina (activity III). Elution with petroleum ether-benzene (1 1) yields, after crystallization from acetone-hexane, 1.27 g (35%) 3j5-acetoxy-17a-ethoxyethynylandrost-5-en-17) -ol mp 138-139° Ho -122°. 

A solution of 500 mg 3 -acetoxypregn-5-en-20-one-[17a,16a-c]-A -pyrazoline in 100 ml of anhydrous dioxane is stirred with a magnetic stirrer and irradiated in a water-cooled quartz reactor with a high pressure Biosol Philips 250 W quartz lamp for 1 hr. The solvent is removed at reduced pressure and the residue is chromatographed on alumina (activity III). Elution with petroleum ether-benzene (3 1) gives 0.2 g (42%) of 3 -acetoxy-16a,17a-methylene-pregn-5-en-20-one mp 193-193.5° after two recrystallizations from methylene dichloride-ethyl acetate. 

A mixture consisting of 0.69 g (10.5 mmoles) of zinc-copper couple, 12 ml of dry ether, and a small crystal of iodine, is stirred with a magnetic stirrer and 2.34 g (0.7 ml, 8.75 mmoles) of methylene iodide is added. The mixture is warmed with an infrared lamp to initiate the reaction which is allowed to proceed for 30 min in a water bath at 35°. A solution of 0.97 g (2.5 mmoles) of cholest-4-en-3/ -ol in 7 ml of dry ether is added over a period of 20 min, and the mixture is stirred for an additional hr at 40°. The reaction mixture is cooled with an ice bath and diluted with a saturated solution of magnesium chloride. The supernatant is decanted from the precipitate, and the precipitate is washed twice with ether. The combined ether extracts are washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue is chromatographed immediately on 50 g of alumina (activity III). Elution with benzene gives 0.62 g (62%) of crystalline 4/5,5/5-methylene-5 -cholestan-3/5-ol. Recrystallization from acetone gives material of mp 94-95° Hd -10°. 

Silica gel Woelm for dry-column chromatography, activity III/30 mm. [according to Brockmann and Schodder, Ber., 74B, 73 (1941)], was supplied by M. Woelm, Eschwege, Germany. 

Activity III alumina is prepared by adding 6% (w/w) of water to neutral alumina of activity grade I. The submitters used a 50x3 cm. glass column for the chromatography. 

Grade 60, activity III silica gel, purchased from W. R. Grace... 

Neutral aluminum oxide (activity III, Woelm) was used. 

I licse modifications are apparently devoid of endocrine activity iii.stead, the compounds possess analgesic activity. Possibly as... 

Partial summary of lipoprotein metabolism in humans. I to VII are sites of action of hypolipidemic drugs. I, stimulation of bile acid and/or cholesterol fecal excretion II, stimulation of lipoprotein lipase activity III, inhibition of VLDL production and secretion IV, inhibition of cholesterol biosynthesis V, stimulation of cholesterol secretion into bile fluid VI, stimulation of cholesterol conversion to bile acids VII, increased plasma clearance of LDL due either to increased LDL receptor activity or altered lipoprotein composition. CHOL, cholesterol IDL, intermediate-density lipoprotein. 

The reaction is cooled to room temperature and approximately 50 mL of toluene and 35 mL of 5% sodium carbonate solution are added. The organic layer is separated, extracted with 3 x 50 mL of 5% sodium carbonate solution, dried over MgS04, and filtered. The toluene is removed on a rotary evaporator and the residue dissolved in 20 mL of methylene chloride. The concentrated solution is absorbed at the top of a column of alumina (2 x 20 cm ca. 100 g of activity III) and eluted with 150 mL of CH2C12 to remove any unreacted pyrazole. The solvent is removed on a rotary evaporator and the solid is recrystallized from 100 mL hexanes to give 10.28 g of the product as white crystals melting at 84-86°C. A second crop of product (0.60 g) can be obtained by concentration of the filtrate, giving an overall yield of 10.88 g (62%) based on 2,2-dimethoxypropane. 

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