Stereoselective reactions of (20 R)-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

• Published in: Steroids Vol. 69; no. 1; pp. 35 - 42
• Main Authors: Magyar, Angéla, Szendi, Zsuzsanna, Forgó, Péter, Mák, Marianna, Görls, Helmar, Sweet, Frederick
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 2004; Elsevier; Elsevier Science
• Subjects: (20 R,23 R)-27-Nor-3,20,23,26-tetrahydroxy-cholest-5-en-22-one-3-acetate; 23-Bromo-(20 R,23 R)-27-nor-3,20,26-trihydroxy-cholest-5-en-22-one; Biochemistry & Molecular Biology; Biological and medical sciences; Cholestanols - chemical synthesis; Cholestanols - chemistry; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; Ketones - chemistry; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Molecular Conformation; Pregnenolone - analogs & derivatives; Pregnenolone - chemistry; Science & Technology; Steroids; Vertebrates: endocrinology; (20 R,23 R)-27-Nor-3,20,23,26-tetrahydroxy-cholest-5-en-22-one-3-acetate; 23-Bromo-(20 R,23 R)-27-nor-3,20,26-trihydroxy-cholest-5-en-22-one; Steroids; ACHYRANTHES; 23-Bromo-(20R,23R)-27-nor-3,20,26-trihydroxy-cholest-5-en-22-one; CHOLESTEROL; (20R,23R)-27-Nor-3,20,23,26-tetrahydroxy-cholest-5-en-22-one-3-acetate; ANALOGS; LIVER; steroids; INSECT METAMORPHOSING SUBSTANCE; BRASSINOLIDE SIDE-CHAIN; PREGNENOLONE; Steroid
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2003.09.011

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.