conicasterol synthesis

Yield:76758-20-8 100%

Reaction Conditions:

with pyridinium chlorochromate in dichloromethane at 20; for 12 h;Inert atmosphere;

Steps:

4.3.3 (24R)-24-Methyl-4α-methyl-5α-cholest-8(14)en-3β-ol 7 and (24R)-24-methyl-4α-methyl-5α-cholest-8(14)en-3α-ol 8

Pyridinium chlorochromate (52mg, 0.24mmol) in CH₂Cl₂ dry (2mL) was added at the solution of conicasterol (50mg, 0.12mmol) in dichloromethane (5mL). The reaction mixture was stirred at room temperature for 12h, then was added water. The aqueous phase was extracted with dichloromethane (3×30mL) and the combined organic phases were dried with Na₂SO₄ and evaporated to dryness. The residue was passed through a short column of silica gel (2g) and eluted with CH₂Cl₂ to give conicasterone [27] (50mg, quantitative yield) as amorphous solid, that was subjected to next step without any purification procedure. Conicasterone was hydrogenated in presence of palladium 5% wt on activated carbon (5mg) in THF dry/ MeOH dry 1:1 v/v (5mL) in an oven-dried 25mL flask. The reaction was stirred at room temperature under H₂ for 1h. Then the mixture was filtered through SiO₂ and the recovered filtrate was concentrated. Purification by HPLC on a Nucleodur Isis 100-5 C18 (5μm; 4.5mm i.d.×250mm) with MeOH/H₂O (999.5:0.5) as eluent (flow rate 1mL/min) afforded 33.6mg (67.3% from conicasterone) of 4β-methyl derivative (t_R=48min) and 16.4mg (32.7% from conicasterone) of 4α-methyl derivative (t_R=52min) as amorphous solids. To a solution of 4β-methyl derivative (30mg, 0.07mmol) in dry methanol (5mL) was added NaBH₄ (13mg, 0.35mmol) at 0°C. After 1h, the reaction was quenched by addition of MeOH (3mL) and then concentrated under vacuo. Ethyl acetate and water were added and the separated aqueous phase was extracted with ethyl acetate (3×30mL). The combined organic phases were washed with water, dried with Na₂SO₄ and concentrated to obtain compound 6 as a white solid (26mg, 87%).

References:

Sepe, Valentina;D'Amore, Claudio;Ummarino, Raffella;Renga, Barbara;D'Auria, Maria Valeria;Novellino, Ettore;Sinisi, Annamaria;Taglialatela-Scafati, Orazio;Nakao, Yoichi;Limongelli, Vittorio;Zampella, Angela;Fiorucci, Stefano [European Journal of Medicinal Chemistry,2014,vol. 73,p. 126 - 134]