fluclorolone acetonide

Originator

Topilar,Syntex,UK,1971

Uses

fluclorolone acetonide is a synthetic glucocorticoid with anti-inflammatory properties. Studies suggest that it is a potent inhibitor of mouse skin tumor promotion and epidermal DNA synthesis.

Definition

ChEBI: Fluclorolone acetonide is a 21-hydroxy steroid.

Manufacturing Process

To 6α-fluoro-16α-hydroxy-hydrocortisone 21-acetate, described by Mills et al, J. Am. Chem. Soc., volume 81, pages 1264 to 1265, March 5, 1959, there was added acetic anhydride in dry pyridine. The reaction mixture was left at room temperature overnight and was then poured with stirring into ice water. The resulting precipitate was filtered, washed with water and crystallized from acetone-hexane to give 6α-fluoro-16α-hydroxy-hydrocortisone-16α,21- diacetate. This was reacted with methane-sulfonyl chloride in dimethyl formamide in the presence of pyridine at 80°C for 1 hour. The mixture was cooled, diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and the ethyl acetate was evaporated. By recrystallization of the residue from acetone-hexane there was obtained 6α-fluoro-Δ4,9(11)-pregnadiene-16α,17α,21-triol-3,20-dione- 16α,21-diacetate.
This was reacted with chlorine to give the dichloropregnene compound, then with selenium dioxide to give the dichloropregnadiene compound. By hydrolysis with methanolic potassium hydroxide there was obtained the free 6α-fluoro-9α,11β-dichloro-Δ1,4-pregnadiene-16α,17α,21-triol-3,20-dione. By treatment with acetone in the presence of perchloric acid, the 16,17-acetonide of 6α-fluoro-9α,11β-dichloro-Δ1,4-pregnadiene-16α,17α,21-triol-3,20-dione was formed.

Therapeutic Function

Glucocorticoid