The syntheses of 3-substituted perfluoroalkyl steroids

• Published in: Steroids Vol. 61; no. 2; pp. 50 - 57
• Main Authors: Williams, John R., Shea, Timothy J.
• Format: Journal Article
• Language: English
• Published: WOBURN Elsevier Inc 01.02.1996; Butterworth-Heinemann; Elsevier Science
• Subjects: 3-perfluoroalkylandrosta-3,5-dien-17-ones; 3β-hydroxy-3α-perfluoroalkylandrost-4-en-17-ones; 3β-hydroxy-3α-perfluoroalkylandrost-5-en-17-ones; Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkylation; Biochemistry & Molecular Biology; Chemistry; dehydration; Endocrinology & Metabolism; Exact sciences and technology; Fluorocarbons - chemical synthesis; glucose-6-phosphate dehydrogenase; Life Sciences & Biomedicine; Molecular Structure; Organic chemistry; Organometallic Compounds; perfluoroalkyl steroids; Preparations and properties; Science & Technology; Steroids; Steroids - chemical synthesis; synthesis; synthesis; 3-perfluoroalkylandrosta-3,5-dien-17-ones; glucose-6-phosphate dehydrogenase; 3β-hydroxy-3α-perfluoroalkylandrost-5-en-17-ones; perfluoroalkyl steroids; 3β-hydroxy-3α-perfluoroalkylandrost-4-en-17-ones; dehydration; KETONES; 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-5-en-17-ones; DEHYDROEPIANDROSTERONE; SPECTRA; perfluoroalkyl steroids 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-4-en-17-ones 3-perfluoroalkylandrosta-3,5-dien-17-ones; DERIVATIVES; Steroid; Glucose-6-phosphate 1-dehydrogenase; Haloalcohol; Enzyme; Enzyme inhibitor; Ketone; In vitro; Biological activity; Alkylation; Allylic compound; Stereoselectivity; Testosterone; Conjugated dienic compound; Fluorine Organic compounds; Oxidoreductases; Secondary alcohol; Chemical synthesis; Enone; Homoallylic compound
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/0039-128X(95)00176-Q

The syntheses of three classes of C-3 perfluoroalkyl substituted steroids are described. They are the 3β-hydroxy-3α-perfluoroalkylandrost-4-en-17-ones ( 5a-c), 3-perfluoroalkylandrosta-3,5-dien-3-ones ( 8a-c) and 3β-hydroxy-3α-perfluoroalkylandrost-5-en-17-ones ( 12a-c). Addition of a series of perfluroalkylorganometallic reagents (R FLi; R F = C 2F 5, C 3F 7, or C 4F 9) to the 3 position of silylated testosterone 2b afforded Δ 4 perfluoroalkyl carbinols 3. In Scheme 1, deprotection with HF and oxidation at the C-17 carbon with PCC produced Δ 4 ketones 5. In Scheme 2 dehydration of 3 with 1,2-phenylenephosphorochloridite and iodine afforded Δ 3,5 dienes 6 which were deprotected and oxidized as above to the C-17 ketones 8. In Scheme 3 isomerization of the double bond of 3 from the C-4 to the C-5 position using the allylic halogenation followed by treatment with lithium aluminum hydride led to the synthesis of the double bond isomer series 12. A new method for dehydration was developed. On average and within experimental error, 3β-hydroxy-3α-perfluoroalkylandrost-5-en-17 ones ( 12a-c) were better than the 3-perfluoroalkylandrosta-3,5-dien-17-ones ( 8a-c) and 3β-hydroxy-3α-perfluoroalkylandrost-4-en-17-ones ( 5a-c) at inhibiting glucose-6-phosphate dehydrogenase.