127-31-1

White Solid

Alflorone Acetate,MSD,US,1954

A mineralocorticoid

A mineralocorticoid.

ChEBI: Fludrocortisone is a C21-steroid, a 3-oxo-Delta(4) steroid, a 20-oxo steroid, a 21-hydroxy steroid, a fluorinated steroid, a mineralocorticoid, a 17alpha-hydroxy steroid and an 11beta-hydroxy steroid. It has a role as an adrenergic agent and an anti-inflammatory drug. It derives from a hydride of a pregnane.

Hydrocortisone acetate is first reacted with phosphorus oxychloride in pyridine to give the corresponding olefin. Then a sequence consisting of hypobromous acid addition, ring closure to the epoxide and ring opening with hydrogen fluoride gives fludrocortisone acetate. Preparation of a crystalline product is described then in US Patent 2,957,013.

Florinef (King).

9-Fluoro-11β,17,21-trihydroxy-pregn-4-ene-3,20-dione acetate

Fludrocortisone acetate is used orally for mineralocorticoid replacement therapy in patients with adrenocortical insufficiency, such as Addison's disease. This drug, introduced in 1954, helped to provide the impetus for the synthesis and biological evaluation of newer halogenated analogues.

Fludrocortisone, 9|á-fluoro-11|?,17|á,21-trihydroxypregn-4-en-3,20- dione (27.2.14), is synthesized from hydrocortisone acetate (27.1.17). In the first stage of synthesis, dehydration of the hydrocortisone molecules is accomplished using phosphorous chloride in pyridine, which forms a product with a double bond at C9¨CC11 27.2.11. The resulting double bond is synthesized into an epoxide by an initial transformation to a bromohydrine using N-bromoacetamide and subsequent dehydrobromination using sodium acetate, which forms 21-O-acetoxy-9d-11|?-epoxy-17|á-hydroxy-4-pregnen-3,20-dione (27.2.12). As described above, the epoxide ring is opened by hydrofluoric acid, which results in the formation of the 21-O-acetate of fludrocortisone 27.2.13. Hydrolysis of the acetyl group of this compound using potassium acetate gives fludrocortisone (27.2.14).