新产品编号:258375
Chemical Name: 16alpha,17alpha-[(R)-Butylidenedioxy]-6alpha,9-difluoro-11beta-hydroxy-21-[2-oxotetrahydrofuran-3(S)-ylsulfanyl]pregn-4-ene-3,20-dione
CAS No. 193408-42-3
项目整合开发状态: Biological Testing
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Fluocinolone acetonide (I) was selectively mesylated at the primary alcohol group by means of methanesulfonyl chloride and pyridine.Treatment of the resulting mesylate (II) with alpha-mercapto-gamma-butyrolactone (IV) in the presence of NaH in THF produced the desired thioether derivative.
合成路线:Ketal exchange of acetonide (I) with butyraldehyde (II) under acidic conditions provides the corresponding butylidene ketal (III).The primary alcohol group of (III) is then mesylated with methanesulfonyl chloride in pyridine to furnish (IV).Subsequent displacement of the mesylate group of (IV) by racemic alpha-mercapto-gamma-butyrolactone (V) gives rise to a mixture of the title compound along with its (R)-epimer (VI),which can be separated employing preparative HPLC.(1,2)
📌 参考资料/链接：
参考文献标题:21-(2-Oxo-tetrahydrofuran)-thio pregnane derivs.,a process for their production and pharmaceutical compsns.containing them
文献作者:Farrell,R.M.; Biggadike,K.(Glaxo Wellcome Inc.)
参考来源:US 6013244; WO 9724367
📄 详细内容
合成路线:Ketal exchange of acetonide (I) with butyraldehyde (II) under acidic conditions provides the corresponding butylidene ketal (III).The primary alcohol group of (III) is then mesylated with methanesulfonyl chloride in pyridine to furnish (IV).Subsequent displacement of the mesylate group of (IV) by racemic alpha-mercapto-gamma-butyrolactone (V) gives rise to a mixture of the title compound along with its (R)-epimer (VI),which can be separated employing preparative HPLC.(1,2)
合成路线:Mitsunobu coupling of alcohol (I) with thioacetic acid affords the thioacetate ester (II),which is further hydrolyzed to thiol (III) by means of hydrazine hydrate in cold THF.Treatment of (R)-alpha-hydroxy-gamma-butyrolactone (IV) with methanesulfonyl chloride and Et3N provides the chiral mesylate (V).This is then condensed with thiol (III) in the presence of K2CO3 in DMF to furnish the title compound.(2)
参考文献标题:Novel glucocorticoid antedrugs possessing a 21-(gamma-lactone) ring
文献作者:Angell,R.M.; Biggadike,K.; Farrell,R.M.; Flack,S.S.; Hancock,A.P.; Irving,W.R.; Lynn,S.M.; Procopiou,P.A.
参考来源:J Chem Soc - Perkins Trans I 2002,(6),831