反应详情

Prednisolone (10 g) was dissolved in 750 ml of methanol and 2.25 g cupric acetate in 750 ml of methanol was added. The solution was mixed and set aside for 20 min. While stirring, the reaction was continued with airation for 1 weak. After adding 500 ml of 0.1% NaHCO3 solution containing 4.5 g EDTA, methanol was evaporated under vacuum. The solution was extracted with ethyl acetate (1,000 ml), dried on anhydrous sodium sulfate and evaporated to dryness (7.5 g). The residue was dissolved in 150 ml methanol and 375 ml water containing 3.75 g NaHSO3 was added. After refluxing for 1 hour, water was evaporated and the residue was extracted with ethyl acetate (500 ml), washed with distilled water, dried on sodium sulfate and evaporated to dryness (3.5 g), which was purified with silica gel column with acetone:dichloromethane:hexane (3:2:5) as a mobile phase. The pooled fraction was evaporated to dryness. Recrystallization four times from methanol gave 1.1 g of methyl (20R)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate (Product 9A) as a colorless platelet, m.p.=254°-255° C., 1H-NMR (Me2SO-d6) δ1.05(s,3H,13-CH3), 1.40(s,3H,10-CH3), 3.62(s,3H,21-OCH3), 4.06(s,1H,20-H), 4.21(m,1H,11-H), 5.91(s,1H,4-H), 6.15(dd,1H,J=10 and 2 Hz,2-H), 7.32(d,1H,J=10 Hz,1-H); MS, m/e 390(M+). The combined remaining solution was evaporated. After dissolving in small amount of methanol, the solution was subjected to preparative HPLC using methanol:water (6:4) as a mobile phase. The eluate was evaporated and crystallized to give 0.8 g of methyl (20S)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate (Product 9B) as a white prism, m.p.=171°- 173° C. 1H-NMR (CDCl3) δ1.15(s,3H,13-CH3), 1.45(s,3H,10-CH3), 3.31(s,3H,21-OCH3), 4.36(s,1H,20-H), 4.43(m,1H,11-H), 6.01(s,1H,4-H), 6.28(dd,1H,J=10 and 2 Hz,2-H), 7.28(d,1H,J=10 Hz,1-H); MS, m/e 390(M+).

1. additionThe solution was mixed
2. customwas evaporated under vacuum
3. extractionThe solution was extracted with ethyl acetate (1,000 ml)
4. dry with materialdried on anhydrous sodium sulfate
5. customevaporated to dryness (7.5 g)
6. dissolutionThe residue was dissolved in 150 ml methanol
7. addition375 ml water containing 3.75 g NaHSO3 was added
8. temperatureAfter refluxing for 1 hour
9. customwater was evaporated
10. extractionthe residue was extracted with ethyl acetate (500 ml)
11. washwashed with distilled water
12. customdried on sodium sulfate
13. customevaporated to dryness (3.5 g), which
14. customwas purified with silica gel column with acetone:dichloromethane:hexane (3:2:5) as a mobile phase
15. customThe pooled fraction was evaporated to dryness
16. customRecrystallization four times from methanol