16a-Hydroxy-9a-fluorohydrocortisone

Chemical Name 9-fluoro-11(3,16a, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione Common Name A -16a-hydroxy-9a-fluorohydrocortisone Structural Formula ... 

The synthesis of halcinonide is summarized in Figure 1, starting with 16a-hydroxy-9a-fluorohydrocortisone (A1 -pregnene-9a-fluoro-llg,16a,17a,21-tetrol-3,20-dione dihydrotriamcinolone, I), which is available commercially.10-13 This tetrahydroxy steroid is slurried in acetone, and then 70% perchloric acid is added slowly. The acetonide, II (9a-fluoro-llg, 16a, 17, 21-tetrahydroxypregn-4-ene-3, 20-dione, cyclic 16,17-acetal with acetone dihydrotriamcinolone-acetonide) precipitates spontaneously from solution. Mesyl chloride is added to the acetonide in pyridine to give the 21-mesylate derivative (dihydrotriamcinolone acetonide-21-mesylate, III). Compound III is dissolved in dimethylformamide, lithium chloride is added and the mixture is refluxed to produce halcinonide (IV), which is recrystallized from a solution of ft-propanol in water. 

Triamcinolone (I, Figure 6) is most commonly synthesized by microbiological dehydrogenation at C-1,2 of 16a-hydroxy-9a-fluorohydrocortisone (II) directly or with intermediate formation of the 16,17-borate ester or 16,21-diacetate (V). A variety of microbiological organisms, capable of 1-dehydrogenation have been reported- - or patented... 

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