INHIBITORS OF STEROL SYNTHESIS - EFFECTS OF FLUORINE SUBSTITUTION AT CARBON-ATOM-25 OF CHOLESTEROL ON ITS SPECTRAL AND CHROMATOGRAPHIC PROPERTIES AND ON 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITYIN CHO-K1 CELLS

25-Fluorocholesterol (III) was prepared by treatment of 25-hydroxychol esterol (IV) with hydrogen fluoride-pyridine. Compounds IlI, IV, and c holesterol (I) were fully characterized by H-1 and C-13 NMR, and stere ochemical assignments were established for the C-22 and C-23 protons. The side-chain proton assignments, which apply to most other sterols w ith a saturated eight-carbon side chain, were based on conformational analysis and comparisons with NMR data for 25, 26, 26, 26, 27, 27, 27- heptafluorocholesterol (II). The chromatographic behavior of I, II, an d III were compared on thin-layer chromatography, high performance liq uid chromatography, and gas chromotography. Major fragment ions in ele ctron-impact mass spectra of III were analogous to ions of either chol esterol or desmosterol, and a similar analogy was observed for the tri methylsilyl ethers. The 25-hydroxysterol IV and the 25-fluorosterol II I differed markedly in their effects on the levels of 3-hydroxy-3-meth ylglutaryl coenzyme, A reductase activity in CHO-Kl cells. Whereas 25- hydroxycholesterol caused a similar to 66% lowering of reductase activ ity in cells at 0.1 mu M, the 25-fluorosterol III had no effect at thi s concentration.