title: Hydrolytic behavior of 5alpha-hydroxy-11beta- and 5beta-hydroxy-11alpha-substituted 19-norsteroids.
abstract: Teutsch G. and Bélanger A. treated 5alpha,10alpha epoxides with Grignard-reagents catalyzed by copper(I) ions. The reaction with steroidal epoxides proceeded with complete regio- and stereospecificity, leading exclusively to the 11beta-substituted compounds. According to our synthetic strategy, the 5,10 epoxide isomers were not separated; instead, the pure 11beta, and in some cases, 11alpha-substituted molecules were isolated after the conjugate addition of the Grignard-reagents, followed by deketalization and dehydration. Surprisingly, appearance of a third compound was generally observed beside the expected deprotected products, and this compound turned out to have a 3-keto-5(10),9(11) structural unit. Starting from pure 3-ethylenedioxy-5alpha,10alpha-epoxy-estr-9(11)-ene-17-one and 3-ethylenedioxy-5beta,10beta-epoxy-estr-9(11)-ene-17-one, four model compounds were synthesized (11alpha- and 11beta-[4-[1,1-(ethylenedioxy)-ethyl]phenyl]-estra-, as well as 11alpha- and 11beta-cyclohexyl-estra-derivatives) to study the process of deprotection and dehydration. 3-keto-5(10),9(11)-derivatives were found to form after deketalization and dehydration only from 11alpha-substituted derivatives, while 11beta-derivatives resulted in only the expected 3-keto-5,9-diene structure. After observing this remarkable difference between the behavior of 11alpha-, 11beta-substituted isomers we decided to take a closer look at the processes of deketalization and dehydration. In order to carry out the hydrolysis under mild conditions, pyridinium paratoluenesulfonate, a weakly acidic salt, was applied. All the intermediate products observed by TLC were isolated. The outcome of the deprotection and elimination reactions can be rationalized by two factors: conjugation of olefins (with the 3-oxo-group or the 11-phenyl group) and orientation of groups to be eliminated.
authors: Department of Steroid Research, Gedeon Richter Ltd., P.O. Box 27, 1475, Budapest, Hungary. e.francsics@richter.hu
authors: Erzsébet
authors: E
authors: Francsics-Czinege
authors: Zoltán
authors: Z
authors: Tuba
authors: Csaba
authors: C
authors: Molnár
authors: Judit
authors: J
authors: Horváth
authors: János
authors: J
authors: Csörgei
authors: György
authors: G
authors: Visky
authors: Gábor
authors: G
authors: Balogh
authors: Marianna
authors: M
authors: Mák
authors: Béla
authors: B
authors: Hegedus
authors: Mária
authors: M
authors: Magyari
authors: János
authors: J
authors: Horváth
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D009654:Norsteroids / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism
chemical_list: D009654:Norsteroids; D003300:Copper