Communications to the Editor 3167 with one mole of bromine and the resulting bromoketone was dehydrohalogenated via semicarbazone formation. Reversal5 of the semicarbazone with pyruvic acid in aqueous acetic acid gave in addition to (I) and (II) the ketone (III) [m.p.6 ca. 237°;[a]p +34.9°(acetone) A^f°H 222 µ (log E 4.03); max* 2.77, 2.98 µ (OH), 5.73, 5.78 µ (acetylated side chain), 6.05 µ (unsaturated ketone); Found: C, 65.66; , 7.05]. (Ill) possessed about 60% of the activity4 of hydrocortisone acetate by the one-day oral mouse liver glycogen assay.Bromination of (II) with two moles of bromine7 followed by dehydrohalogenation with collidine afforded the dienone (IV) [m.p. ca. 237°; [u]d + 100.9°( acetone); A^OH 239 µ (log E 4.19); Agfx0< (2 hr.) 310 µ (4.06), 262.5 µ (4.18); A"uJxo1 2.92, 3.02 µ (OH), 5.74, 5.82 µ (acetylated side chain), 6.0 µ (unsaturated ketone), 6.12, 6.21 µ (diene system); Found: C, 65.66; H, 6.74] and the isomeric dienone (V) [m.p. ca. 208°6; [qJd +106°( acetone), A^OH 281 µ (log E 4.40), A"uaJ°' 2.85, 3.06 µ (OH), 5.70, 5.81 µ (acetylated side chain), 6.12, 6,18 µ (conjugated dienone system); Found: C, 65.86; H, 6.99]. 1 -Dehydro-9 -fluorohy drocortisone acetate (IV) possessed about 25 times the activity of hydrocortisone acetate in the mouse liver glycogen assay and in the rat systemic granuloma inhibition test.4 It is, therefore, the most potent glucocorticoid known. It is of interest to note that enhanced glucocorticoid activity was reported recently8 for 1 -dehydrocortisone and 1dehydrohydrocortisone acetate, which possess the same chromophoric system as (IV). CH2OAc I, Double bond between C4-Cs. II, H at C5 formulated as "a". III, Double bond between Ci-C2; H at C5 formulated as "a".IV, Double bonds between Ci-C2 and C4-C6. V, Double bonds between C4-C5and Cs-C-.
