(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Five portions of 4-bromobutanoylchloride (0.35 ml×5) and potassium carbonate (0.4 g×5) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5 and stirred for 5 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 portions of 4-chlorobutanoylchloride (0.32 ml×4) and triethylamine (0.3 g×4) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5, and stirred for 3 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. The crude residue was ground with hexane and CH2Cl2 to give a white solid with a 53% yield by weight, which had a melting point (m.p.) of 155° C. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4) to give a white solid with a 53% yield by weight, which a melting point (m.p.) of 155° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: From 20 g of Primycin and 40.0 g of N-methyl-pyrrolidone-2 a gel is prepared at 70° C., whereupon nystatin and hydrocortisone are added at room temperature under constant stirring. A very viscous solution is obtained which becomes gelous on standing for 24 hours. are added at room temperature under constant stirring A very viscous solution is obtained which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Hydrocortisone (3.65 g, 10 mmol) in acetonitrile (450 ml), succinic anhydride (1.65 g, 15 mmol) and DIEA (1.7 ml, 10 mmol) were added and the reaction mixture stirred at room temperature for 36 h. HPLC analysis of the reaction mixture showed 93% of the title compound. The solvent was evaporated and the residue redissolved in ethyl acetate and washed with water. The ethyl acetate phase was evaporated under reduced pressure and the residue triturated in diethyl ether to obtain 4.4 g of white powder in 95% yield. RtI 5.94′.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Hydrocortisone (3.65 g, 10 mmol) in acetonitrile (450 ml), succinic anhydride (1.65 g, 15 mmol) and DIEA (1.7 ml, 10 mmol) were added and the reaction mixture stirred at room temperature for 36 h. HPLC analysis of the reaction mixture showed 93% of the title compound. The solvent was evaporated and the residue redissolved in ethyl acetate and washed with water. The ethyl acetate phase was evaporated under reduced pressure and the residue triturated in diethyl ether to obtain 4.4 g of white powder in 95% yield. RtI 5.94′.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Hydrocortisone (3.65 g, 10 mmol) in acetonitrile (450 ml), succinic anhydride (1.65 g, 15 mmol) and DIEA (1.7 ml, 10 mmol) were added and the reaction mixture stirred at room temperature for 36 h. HPLC analysis of the reaction mixture showed 93% of the title compound. The solvent was evaporated and the residue redissolved in ethyl acetate and washed with water. The ethyl acetate phase was evaporated under reduced pressure and the residue triturated in diethyl ether to obtain 4.4 g of white powder in 95% yield. RtI 5.94'.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Five portions of 4-bromobutanoylchloride (0.35 ml×5) and potassium carbonate (0.4 g×5) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5 and stirred for 5 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Five portions of 4-bromobutanoylchloride (0.35 ml×5) and potassium carbonate (0.4 g×5) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5 and stirred for 5 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 portions of 4-chlorobutanoylchloride (0.32 ml×4) and triethylamine (0.3 g×4) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5, and stirred for 3 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. The crude residue was ground with hexane and CH2Cl2 to give a white solid with a 53% yield by weight, which had a melting point (m.p.) of 155° C. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4) to give a white solid with a 53% yield by weight, which a melting point (m.p.) of 155° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 portions of 4-chlorobutanoylchloride (0.32 ml×4) and triethylamine (0.3 g×4) were added in 24 hours to a solution of hydrocortisone (1 g) in CHCl3 dried over P2O5, and stirred for 3 days. The solution was treated with water, the organic phase was separated, dried (Na2SO4) and deprived of the solvent at reduced pressure. The crude residue was ground with hexane and CH2Cl2 to give a white solid with a 53% yield by weight, which had a melting point (m.p.) of 155° C. dried over P2O5 The solution was treated with water the organic phase was separated dried (Na2SO4) to give a white solid with a 53% yield by weight, which a melting point (m.p.) of 155° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.63 g (10 mmol) of hydrocortisone in 150 ml of dichloromethane is mixed with 2.34 g (10.8 mmol) of N-(tert -butoxycarbonyl)-valine, 500 mg (4.1 mmol) of 4-dimethylaminopyridine and 3.1 g (15 mmol) of dicyclohexylcarbodiimide. The solution is stirred for 3 hours at room temperature, the precipitate that is produced is suctioned off and washed with dichloromethane. The filtrate is concentrated by evaporation in a vacuum. The chromatography on silica gel (hexane→hexane/ethyl acetate 1:1) provides 2.87 g (51%) of (2S)-2-((1,1-dimethylethoxycarbonyl)-amino)-3-methylbutyric acid [11β,17,21-trihydroxy-3,20-dioxo-pregn-4-en-21-yl] ester. Crystallization from dichloromethane/diisopropyl ether. the precipitate that is produced washed with dichloromethane The filtrate is concentrated by evaporation in a vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydrocortisone (3.62 g, 0.01 mole) and N,N-(N'-methyl-3'-azapentamethylene)succinamic acid (2.00 g, 0.01 mole) in 15 ml pyridine at room temperature was added dicyclohexylcarbodiimide (2.00 g, 0.01 mole). After stirring the reaction mixture 10 minutes, 25 ml dichloromethane was added to it to keep the suspension, which had resulted, sufficiently fluid for stirring. After stirring overnight, the reaction was filtered. The residue was washed twice with CH2Cl2 and air dried to give 1.65 g (84% yield) dicyclohexylurea. The filtrate was concentrated in vacuo to give a light brown foam which was in turn triturated 2 hours with 10 ml CH2Cl2 to give a suspension which was filtered. The residue was dried in the vacuum oven 3 hours at 40° C. after a preliminary NMR showed contamination of the product with CH2Cl2. The resulting finely crystalline, off-white powder was the desired product: 2.70 g, 51% yield; mp 159°-163° C.; NMR (DMSO-d6) δ5.53 (s, 1, O=C-CH=C-), 5.32 (m, 1, C-OH), 4.91 (ABq, 2, JAB=17 Hz, ΔνAB =18 Hz, O=C-CH2 -O), 4.29 (m, 2, CH-OH), 3.41 (m, 8, -N(CH2CH2)N-), 2.59 (s, 3, N-CH3), 1.37 (s, 3, C-CH3), 0.78 (s, 3, C-CH3), 2.7-0.8 (m, 21, CH, CH2); IR (KBr) 3400 cm-1 (s) (OH), 1730 cm-1 and 1710 cm-1 (s) (C-C=O and O-C=O) and 1640 and 1615 cm-1 (s) (O=C-CH=C, N-C=O); [α]24D=+122° (C=0.5, dioxane); TLC (silica gel, MeOH) Rf 0.27. was added to it which had resulted After stirring overnight the reaction was filtered The residue was washed twice with CH2Cl2 and air dried