Ciclesonide, BTR-15, B-9207-015, BY-9010, Alvesco-药物合成数据库

【药物名称】Ciclesonide, BTR-15, B-9207-015, BY-9010, Alvesco

化学结构式(Chemical Structure):

参考文献No.	17460
标题:	Acetals and esters of 16alpha-hydroxyprednisolone and fluocinolone
作者:	Calatayud, J.; Conde, J.R.; Luna, M. (Byk Elmu SA)
来源:	BE 1005876; CH 683343; DE 4129535; ES 2034893; FR 2666585; GB 2247680; JP 1992257599; US 5482934

合成路线图解说明: The acylation of 11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione (I) with isobutyric anhydride in pyridine gives the 16,17,21-triester (III), which is condensed with cyclohexanecarbaldehyde (IV) by means of HCl and HClO4 in dioxane yielding the cyclic ketal (Va-b) as a diastereomeric mixture. Finally, this mixture is resolved by preparative HPLC over Lichrosorb RP-18 affording the desired (R)-isomer, the target compound. Alternatively, the monoacylation of the ketal 11beta,16alpha,17alpha,21-tetrahydroxypregan-1,4-diene-3,20-dione 16,17-O-cyclohexylmethylene ketal (VI) with isobutyric anhydride (II) by means of K2CO3 in acetone gives the previously described diastereomeric mixture (Va-b), which is resolved by crystallization in ethanol/water.

参考文献No.	44482
标题:	Process for R-epimer enrichment of 16,17-acetal derivs. of 21-acyloxy pregnan-1,4-dien-11beta,16alpha,17alpha-triol-3,20-dione derivs.
作者:	Gutterer, B.; Amschler, H.; Flockerzi, D. (Byk Gulden Lomberg Chemische Fabrik GmbH)
来源:	DE 19635498; WO 9809982

合成路线图解说明: The acylation of 11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione (I) with isobutyric anhydride in pyridine gives the 16,17,21-triester (III), which is condensed with cyclohexanecarbaldehyde (IV) by means of HCl and HClO4 in dioxane yielding the cyclic ketal (Va-b) as a diastereomeric mixture. Finally, this mixture is resolved by preparative HPLC over Lichrosorb RP-18 affording the desired (R)-isomer, the target compound. Alternatively, the monoacylation of the ketal 11beta,16alpha,17alpha,21-tetrahydroxypregan-1,4-diene-3,20-dione 16,17-O-cyclohexylmethylene ketal (VI) with isobutyric anhydride (II) by means of K2CO3 in acetone gives the previously described diastereomeric mixture (Va-b), which is resolved by crystallization in ethanol/water.