Ultralan,Schering,W. Germany,1965
Fluocortolone is a glucocorticoid used in the treatment of several conditions, including hemorrhoids. Fluocortolone is similar to Fluocortin, but with one less keto group.
(a) 16α-Methyl-6α-Fluoro-δ4-11β,21-Diol-3,20-Dione:16α-methyl-6α-fluoro-δ4-
pregnene-21-ol-3,20-dione-21-acetate (MP 132°/134° to 138°C, UVε238=
15,000) is hydroxylated with Curvularia lunata in 11β-position using the
fermentation method whereby the 21-acetate group is simultaneously
saponified. The hitherto unknown starting material 16α-methyl-6α-fluoro-δ4-
pregnene-21-ol-3,20-dione-21-acetate is obtained from 16α-methyl-δ5-
pregnene-3β,21-diol-20-one-21-acetate, MP 152° to 154°C, by the addition of
bromofluorine (from N-bromoacetamide and hydrogen fluoride) onto the 5-6
double bond, oxidation of the 3β-hydroxyl group with chromic acid,
introduction of the δ4-double bond by splitting of the hydrogen bromide and
acid isomerization of the 6β-fluoro substituent to the 16α-methyl-6α-fluoro-δ4-
pregnene-21-ol-3,20-dione-21-acetate. By chromatographic purification on
silica gel the 16α-methyl-6α-fluoro-δ4-pregnene-11β,21-diol-3,20-dione is: MP
166°/167° to 171°C.
(b) 16α-Methyl-6α-Fluoro-δ4-Pregnene-11β,21-Diol-3,20-Dione-21-Acetate:By
reaction of the compound of (a) with acetic anhydride in pyridine at room
temperature, the acetate is obtained and recrystallized from ethyl acetate, MP
248°/249° to 251°C.
(c) 16α-Methyl-6α-Fluoro-δ1,4-Pregnadiene-11β,21-Diol-3,20-Dione:16α-
methyl-6α-fluoro-δ4-pregnene-11β,21-diol-3,20-dione is dehydrogenated with
Corynebacterium simplex. The extraction residue is subjected to
chromatography on silica gel and after recrystallization there is obtained from
methylene chloride-isopropyl ether 16α-methyl-6α-fluoro-δ1,4-pregnadiene-
11β,21-diol-3,20-dione, MP 180°/181° to 182°C.
