Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one (4) has been prepared as part of a program to synthesize 15-ketosterols that are not readily metabolized to cholesterol or side-chain oxygenated species. Saponification of 3 beta-acetoxy-5 alpha-chola-8(14),23-dien-15-one (5) followed by lithium-ammonia reduction with a bromobenzene quench gave 3 beta-hydroxy-5 alpha-chol-23-en-15-one (6). Addition of (CF3)2CFI to 6 in the presence of triethylborane gave an iodide preparation, which was reduced to 4 with tributyltin hydride (71% overall yield of 4 from 5). The 23-iodide preparations consisted of 6:1 mixtures of (23R)-3 beta-hydroxy-23-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one (9a) and its C-23 epimer 9b with variable amounts of 4. Compound 4 was also prepared by lithium-ammonia reduction of the delta 8(14) analogs of 4 and iodides 9a and 9b. The presence of small amounts of 6 in the latter product suggested a side reaction involving cleavage of the C24-C25 bond with loss of a (CF3)2CF radical. Also prepared were 25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestane-3 beta, 15 alpha-diol, its 15 beta epimer, the 7 alpha-methyl analog of 4, 3 beta-hydroxy-7 alpha-methyl-5 alpha-cholestan-15-one (16), and (25R)-3 beta,26-dihydroxy-5 alpha-cholestan-15-one. Full 1H and 13C-NMR data of high precision with complete signal assignments are given for all new compounds. Definitive 1H-NMR stereochemical assignments of the C-24 protons were established for most sterols with a C8H17 side chain based on analysis of the downfield H-24 resonance in a 750-MHz spectrum of 16. Detailed electron-impact mass spectral data are presented together with a summary of major fragmentation patterns for 15-hydroxy- and 15-ketosteroids with and without a delta 8(14) bond.

Type

Journal article

Journal

Chem Phys Lipids

Publication Date

25/04/1997

Volume

86

Pages

95 - 119

Keywords

Anticholesteremic Agents, Cholestenones, Cholesterol, Enzyme Inhibitors, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Structure, Sterols