ROSSIJSKAJA FEDERATSIJA; OT IMENI KOTOROJ VYSTUPAET MINISTERSTVO PROMYSHLENNOSTI I TORGOVLI ROSSIJSKOJ FEDERATSII (MINPROMTORG ROSSII)
发明人:
KAZANTSEV ALEKSEJ VITALEVICH (KAZANTSEV ALEXEY VITALIEVICH),Казанцев Алексей Витальевич (Kazantsev Alexey Vitalievich),SAVINOVA TATJANA STEPANOVNA (SAVINOVA TATYANA STEPANOVNA),Савинова Татьяна Степан
申请号：
RU2013132348/04
公开号：
RU0002532902C1
申请日:
2013.07.12
申请国别(地区):
RU
年份:
2014
代理人:
摘要：
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 dexam
