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Osaterone acetate, TZP-4238, Hipros

17-alpha-乙酰氧基-6-氯-2-氧杂-4,6-孕甾二烯-3,20-二酮Chemical Name: 17alpha-Acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione; 6-Chloro-17-hydroxy-2-oxapregna-4,6-diene-3,20-dione 17-acetate; 2-Oxachlormadinone acetate
CAS No. 105149-00-6
项目整合开发状态: Pre-Registered
项目研究机构: Teikoku Hormone (Originator)
合成路线:This compound can be prepared by two different ways:1) The dehydrogenation of 17alpha-acetoxy-6-chloropregna-4,6-diene-3,20-dione (I) with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in refluxing dioxane gives 17alpha-acetoxy-6-chloropregna-1,4,6-triene-3,20-trione (II),which is oxidized with OsO4 and NaIO4 in refluxing dioxane,yielding 17alpha-acetoxy-6-chloro-1alpha-hydroxy-2-oxapregna-4,6-diene-3,20-dion e (III).Finally,this compound is treated with NaBH4 and NaHCO3 in methanol-THF.2) Epoxidation of 17alpha-acetoxypregna-1,4,6-triene-3,20-dione (IV) with m-chloroperbenzoic acid (MCPBA) in chloroform gives 17alpha-acetoxy-6alpha,7alpha-epoxypregnan-1,4-diene-3,20-dione (V),which is treated with ozone in pyridine at -30 C,yielding 17alpha-acetoxy-6alpha,7alpha-epoxy-1alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VI).The reduction of (VI) with NaBH4 in methanol-THF followed by epoxide ring opening with concentrated HCl affords 17alpha-acetoxy-6beta-chloro-7alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VII),which is acetylated with acetic anhydride in pyridine to the diacetate (VIII).Finally,this compound is treated with potassium acetate in hot DMF to afford the title product.
📌 参考资料/链接:
参考文献标题:2-Oxa- or aza-pregnane derivs
文献作者:Shibata,K.; Yamakoshi,N.; Koizumi,N.; Takegawa,S.; Shimazawa,E.; Mieda,M.(Teikoku Hormone Manufacturing Co.,Ltd.)
参考来源:AU 8654245; EP 0193871; ES 8801510; ES 8801669; ES 8801670; ES 8801928; JP 1986204198; JP 1986204199; US 4735103; US 4914106

📄 详细内容


合成路线:This compound can be prepared by two different ways:1) The dehydrogenation of 17alpha-acetoxy-6-chloropregna-4,6-diene-3,20-dione (I) with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in refluxing dioxane gives 17alpha-acetoxy-6-chloropregna-1,4,6-triene-3,20-trione (II),which is oxidized with OsO4 and NaIO4 in refluxing dioxane,yielding 17alpha-acetoxy-6-chloro-1alpha-hydroxy-2-oxapregna-4,6-diene-3,20-dion e (III).Finally,this compound is treated with NaBH4 and NaHCO3 in methanol-THF.2) Epoxidation of 17alpha-acetoxypregna-1,4,6-triene-3,20-dione (IV) with m-chloroperbenzoic acid (MCPBA) in chloroform gives 17alpha-acetoxy-6alpha,7alpha-epoxypregnan-1,4-diene-3,20-dione (V),which is treated with ozone in pyridine at -30 C,yielding 17alpha-acetoxy-6alpha,7alpha-epoxy-1alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VI).The reduction of (VI) with NaBH4 in methanol-THF followed by epoxide ring opening with concentrated HCl affords 17alpha-acetoxy-6beta-chloro-7alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VII),which is acetylated with acetic anhydride in pyridine to the diacetate (VIII).Finally,this compound is treated with potassium acetate in hot DMF to afford the title product.

参考文献标题:Antiandrogen.I.2-Azapregnane and 2-oxapregnane steroids
文献作者:Shibata,K.; Takegawa,S.; Koizumi,N.; Yamakoshi,N.; Shimazawa,E.
参考来源:Chem Pharm Bull 1992,40(4),935-41


合成路线:This compound can be prepared by two different ways:1) The dehydrogenation of 17alpha-acetoxy-6-chloropregna-4,6-diene-3,20-dione (I) with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in refluxing dioxane gives 17alpha-acetoxy-6-chloropregna-1,4,6-triene-3,20-trione (II),which is oxidized with OsO4 and NaIO4 in refluxing dioxane,yielding 17alpha-acetoxy-6-chloro-1alpha-hydroxy-2-oxapregna-4,6-diene-3,20-dion e (III).Finally,this compound is treated with NaBH4 and NaHCO3 in methanol-THF.2) Epoxidation of 17alpha-acetoxypregna-1,4,6-triene-3,20-dione (IV) with m-chloroperbenzoic acid (MCPBA) in chloroform gives 17alpha-acetoxy-6alpha,7alpha-epoxypregnan-1,4-diene-3,20-dione (V),which is treated with ozone in pyridine at -30 C,yielding 17alpha-acetoxy-6alpha,7alpha-epoxy-1alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VI).The reduction of (VI) with NaBH4 in methanol-THF followed by epoxide ring opening with concentrated HCl affords 17alpha-acetoxy-6beta-chloro-7alpha-hydroxy-2-oxapregn-4-ene-3,20-dione (VII),which is acetylated with acetic anhydride in pyridine to the diacetate (VIII).Finally,this compound is treated with potassium acetate in hot DMF to afford the title product.
参考文献标题:Osaterone Acetate
文献作者:Mealy,N.; Castar,J.; Prous,J.
参考来源:Drugs Fut 1993,18(6),516


产品链接: CAS No. 105149-00-6››