睾酮

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution containing 14.7 g of testosterone in 140 ml of toluene, 65 ml methylene chloride, 25 ml of ether and 2.0 ml of water is added 13.65 g of lithium iodide and the resulting mixture is stirred for 2 hours. To aid in filtration of the mixture 160 ml toluene and 50 ml ether is added. The solids are removed by filtration and washed with 2×50 ml of cold wash solution (4:1, hexane:methylene chloride) followed by 100 ml of hexane. The solids are dried `in vacuo` for 16 hours, then under high vacuum for 24 hours to yield 31.73 g of testosterone lithium iodide complex. To aid in filtration of the mixture 160 ml toluene and 50 ml ether is added The solids are removed by filtration washed with 2×50 ml of cold wash solution (4:1, hexane:methylene chloride) The solids are dried `in vacuo` for 16 hours under high vacuum for 24 hours to yield 31.73 g of testosterone lithium iodide complex

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: By the method of example 1, testosterone (2.88 g, 10 mM), potassium tert-butoxide (3.40 g, 30 mM) and iso-propylnitrate (1.01 ml) are reacted to yield 17β-hydroxy-4-nitroandrost-4-en-3-one, m.p. 158°-160° C. (acetone-hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Stock solution of estradiol and testosterone were diluted with water and mixed with Freund's incomplete adjuvant. This was mixed continuously for 1 minute and either 100 ul (E1 and E3) or 200 ul (E2 and E4) were injected subcutaneously. Estrogen or testosterone release was continuous over six days. Peak measured levels were obtained in 24 hr as shown in previous studies. Animals in the E1 and E3 groups were targeted to receive 100-300 pg/ml estrogen and groups E2 and E4 were targeted to receive 400-800 pg/ml of estrogen. Animals in T1 and T2 grouping were targeted to receive 100 pg/ml testosterone. mixed with Freund's incomplete adjuvant This was mixed continuously for 1 minute were obtained in 24 hr

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This synthesis is depicted in FIG. 2. Several methods are known for the conversion of testosterone into Androsta-4,16-dien-3-one (Brooksbank et al., Biochem. J. (1950) 47:36). Alternatively, thermolysis (460°) of the methyl carbonate of testosterone gives Androsta-4,16-dien-3-one in 90% yield. 17β-Methoxycarbonyloxy-androst-4-en-3-one (IV) was prepared from testosterone (III. Fluka) with methyl chloroformate/pyridine (a) in 76% yield (after recrystallization from MeOH). M.p. 140°-141°, [a]D =+95.4° (C=1.10) - IR. (CDCl3): 1740s, 1665s, 1450s, 1280s, 1H-NMR. (360 Mhz): 0.87 (s, 3 H); 1.20 (s, 3 H); 3.77 (s, 3 H); 4.53 (br. t, J=8, 1 H); 5.75 (s, 1 H). A solution of the methyl carbonate IV in toluene was pyrolyzed (b) as described for 1. Recrystallization of the crude product from acetone at RT. gave pure ketone 4 in 90% yield. M.p. 127°-129.5°, [a]D =+118.9° (c=1.32) ([3]: m.p. 131.5°-133.5° (hexane), [a]D16 +123°±3.5° (c=1.03)). - IR. (CDCl3): 3050w, 1660s, 1615m. - 1H-NMR. (360 Mhz): 0.82 (s, 3 H); 1.22 (s, 3 H); 5.70 (m, 1 H); 5.73 (s, 1 H); 5.84 (m, 1 H). M.p. 140°-141°, [a]D =+95.4° (C=1.10) - IR Recrystallization of the crude product from acetone at RT

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: testosterone (XII) is reacted with potassium butoxide and methyl iodide to form 4-methyl-17β-hydroxyandrost-4-en-3-one

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: testosterone (XII) is reacted with potassium butoxide and methyl iodide to form 4-methyl-17β-hydroxyandrost-4-en-3-one

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2.884 g (0.01 mol) of testosterone in 30 ml of dry benzene was added 1.008 g (0.012 mol) of sodium bicarbonate; then, while stirring, there were introduced dropwise 1.888 g (0.012 tool) of bromoacetyl chloride over a 5 minute period. The reaction mixture was then stirred under reflux for 6 hours until no testosterone could be traced by TLC. (Plates of Silica Gel G and a CHCH3 /CH3OH system were used.) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo and the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%). IR (KBr) 1735 (C=O), 1660 (C=O) cm-1. PMR as expected. The product has the formula: ##STR1506## The reaction mixture was then stirred ) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2.884 g (0.01 mol) of testosterone in 30 ml of dry benzene was added 1.008 g (0.012 mol) of sodium bicarbonate; then, while stirring, there were introduced dropwise 1.888 g (0.012 tool) of bromoacetyl chloride over a 5 minute period. The reaction mixture was then stirred under reflux for 6 hours until no testosterone could be traced by TLC. (Plates of Silica Gel G and a CHCH3 /CH3OH system were used.) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo and the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%). IR (KBr) 1735 (C=O), 1660 (C=O) cm-1. PMR as expected. The product has the formula: ##STR1506## The reaction mixture was then stirred ) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2.884 g (0.01 mol) of testosterone in 30 ml of dry benzene was added 1.008 g (0.012 mol) of sodium bicarbonate; then, while stirring, there were introduced dropwise 1.888 g (0.012 mol) of bromoacetyl chloride over a 5 minute period. The reaction mixture was then stirred under reflux for 6 hours until no testosterone could be traced by TLC. (Plates of Silica Gel G and a CHCH3 /CH3OH system were used.) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo and the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%). IR (KBr) 1735 (C=O), 1660 (C=O) cm-1. PMR as expected. The product has the formula: ##STR1527## The reaction mixture was then stirred ) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo the residue was recrystallized from methanol, m.p. 144°-145° C., yield 3.2 g (78%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Stock solution of estradiol and testosterone were diluted with water and mixed with Freund's incomplete adjuvant. This was mixed continuously for 1 minute and either 100 ul (E1 and E3) or 200 ul (E2 and E4) were injected subcutaneously. Estrogen or testosterone release was continuous over six days. Peak measured levels were obtained in 24 hr as shown in previous studies. Animals in the E1 and E3 groups were targeted to receive 100-300 pg/ml estrogen and groups E2 and E4 were targeted to receive 400-800 pg/ml of estrogen. Animals in T1 and T2 grouping were targeted to receive 100 pg/ml testosterone. mixed with Freund's incomplete adjuvant This was mixed continuously for 1 minute were obtained in 24 hr

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Stock solution of estradiol and testosterone were diluted with water and mixed with Freund's incomplete adjuvant. This was mixed continuously for 1 minute and either 100 ul (E1 and E3) or 200 ul (E2 and E4) were injected subcutaneously. Estrogen or testosterone release was continuous over six days. Peak measured levels were obtained in 24 hr as shown in previous studies. Animals in the E1 and E3 groups were targeted to receive 100-300 pg/ml estrogen and groups E2 and E4 were targeted to receive 400-800 pg/ml of estrogen. Animals in T1 and T2 grouping were targeted to receive 100 pg/ml testosterone. mixed with Freund's incomplete adjuvant This was mixed continuously for 1 minute were obtained in 24 hr

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Testosterone is treated with methyl chloroformate in pyridine to give 17β-methoxycarbonyloxyandrost-4-en-3-one in 76% yield after recrystallization from methanol. A solution of the 17β-methoxycarbonyloxyandrost-4-en-3-one in toluene is pyrolyzed at 460° C., and the crude product is recrystallized from acetone at room temperature to give androsta-4,16-dien-3-one in 90% yield. The androsta-4,16-dien-3-one is reduced at −55° with lithium tris(1,2-dimethylpropyl)hydridoborate in tetrahydrofuran to give a mixture of androsta-4,16-dien-3β-ol and androsta-4,16-dien-3α-ol; and chromatography on silica gel using dichloromethane/ethyl acetate gives pure androsta-4,16-dien-3β-ol and pure androsta-4,16-dien-3α-ol, each in 48% yield. These may be recrystallized (androsta-4,16-dien-3β-ol from cyclohexane at room temperature and androsta-4,16-dien-3α-ol from petroleum ether at −30° C.).