METHOD OF OBTAINING 11BETA, 17 ALPHA, 21-TRIHYDROXY-16ALPHA-METHYL-9ALPHA-FLUOROPREGNA-1,4-DIENE-3,20-DIONE (DEXAMETHAZONE) FROM PHYTOSTEROL Russian patent published in 2014 - IPC C12P33/16 C07J5/00 A61K31/573 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining dexamethasone from phytosterols (β-sitosterol, campesterol, stigmasterol, brassicasterol) by a method, including a sequence of microbiological and chemical reactions, namely: microbiological oxidative elimination of a side chain of phytosterol with the formation of 9α-hydroxyandrost-4-en-3,17-dione by culture Mycobacterium sp.VKM Ac-1817D; processing 9α-hydroxyandrost-4-en-3,17-dione with mineral acid in a medium of aprotic organic solvent with the formation of 9(11)-double bond; 17-hydrocyanation of androst-4,9(11)-diene-3,17-dione; protection of 3-ketogroup of 17α-hydroxy-17β-cyanandrost-4,9(11)-dien-3-one by the formation of cyclic ketal, protection of 17α-hydroxygroup by the formation of 1-alkoxyethyl ether, alkylation of 17-CN-group with further removal of protective groups, C21-acetoxylation of the obtained 17α-hydroxy-20-ketopregn with the application of a method of direct C21-iodination; etherification of 17α-hydroxygroup of 21-acetoxy-17α-hydropregn-4,9(11)-dien-3,20-dione and elimination of 17α-acetoxygroup, microbiological 1,2-dehydration of 21-acetoxypregn-4,9(11),16-triene-3,20-dione with a culture of Nocardioides simplex VKM Ac-2033D with the formation of 21-acetoxypregn 1,4,9(11),16-tetraene-3,20-dione, reaction of the catalytic 1,4-connection of the Grignard reagent by Δ16-20-ketosystem with the formation of magnesiumhaloidderivative of 21-acetoxy-20-hydroxy-16a-methylpregn-1,4,9(11),17(20)-tetraen -3-one; introduction of 17α-hydroperoxygroup by autooxidation of the latter; reduction of 17α-hydroperoxygroup in 17α-hydroxyl; 9,11-bromohydroxylation of 21-acetoxy-17α-hydroxyl-16α-methylpregn-1,4,9(11)-triene-3,20-dione and further 9β(11)-epoxidation with the simultaneous hydrolysis of the acetoxygroup at C21; disclosure of 9β(11)-epoxy ring of 17α,21-dihydroxy-16α-methyl-9β(11)epoxypregn-1,4-diene-3,20-dione by the action of hydrofluoric acid.

EFFECT: method makes it possible to obtain dexamethasone with the 23 percent output.

24 cl, 3 tbl, 16 ex