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-2 H -pyran attached via a CC bond to the C-20 position ( 1 ), stereoselectively reacts with m -chloroperoxybenzoic acid in methanol at −5 °C. Acid-catalyzed hydrolysis of the isolated intermediates gives good yields of mostly a new 27-norcholesterol analog: (20 R ,23 R )-3,20,23,26-tetrahydroxy-27-norcholest-5-en-22-one-3-acetate ( 2a , and a smaller amount of its 23 S enantiomer 2b ). Three different conditions of epoxidation and methanolysis followed by acid-catalyzed hydrolysis typically produce ∼2:1 ratios of the 23 R :23 S diastereoisomers with a C-23 hydroxy group at the new asymmetric center. Bromine also reacts stereoselectively with (20 R )-3,20-dihydroxy-(3′,4′-dihydro-2′ H -pyranyl)-5-pregnene ( 4 ) giving mostly (20 R ,23 R )-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-23 R 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-2 H -pyranyl ring in 1 and 4 .