title: Stereoselective reactions of (20R)-3,20-dihydroxy-(3',4'-dihydro-2'H-pyranyl)-5-pregnene derivatives form 27-nor-3,20,23,26-tetrahydroxy-cholesten-22-ones and related bromo ketones.
abstract: The previously reported analog of pregnenolone having a 3,4-dihydro-2H-pyran attached via a Cz.sbnd;C bond to the C-20 position (1), stereoselectively reacts with m-chloroperoxybenzoic acid in methanol at -5 degrees C. Acid-catalyzed hydrolysis of the isolated intermediates gives good yields of mostly a new 27-norcholesterol analog: (20R,23R)-3,20,23,26-tetrahydroxy-27-norcholest-5-en-22-one-3-acetate (2a, and a smaller amount of its 23S enantiomer 2b). Three different conditions of epoxidation and methanolysis followed by acid-catalyzed hydrolysis typically produce approximately 2:1 ratios of the 23R:23S diastereoisomers with a C-23 hydroxy group at the new asymmetric center. Bromine also reacts stereoselectively with (20R)-3,20-dihydroxy-(3',4'-dihydro-2'H-pyranyl)-5-pregnene (4) giving mostly (20R,23R)-23-bromo-3,20,26-trihydroxy-27-norcholest-5-en-22-one (7a). Thus both major steroidal products 2a and 7a have the same C-23R configuration. Assignment of molecular structures and the absolute configurations to 1 and 2a were based on elemental analysis, mass spectra, nuclear magnetic resonance, FTIR infrared spectroscopic analysis and X-ray crystallography. Mechanisms are discussed for stereochemical selectivity during epoxidation and bromination of the 3,4-dihydro-2H-pyranyl ring in 1 and 4.
authors.affiliation: Department of Organic Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Angéla
authors.initials: A
authors.lastname: Magyar
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Szendi
authors.forename: Péter
authors.initials: P
authors.lastname: Forgó
authors.forename: Marianna
authors.initials: M
authors.lastname: Mák
authors.forename: Helmar
authors.initials: H
authors.lastname: Görls
authors.forename: Frederick
authors.initials: F
authors.lastname: Sweet
mesh_terms: D002777:Cholestanols / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D002777:Cholestanols; D007659:Ketones; D011284:Pregnenolone