86361-68-4

Usage

InChI:InChI=1/C27H45FO/c1-17(2)7-6-8-18(3)21-9-10-22-20-16-25(28)24-15-19(29)11-13-27(24,5)23(20)12-14-26(21,22)4/h17-23,29H,6-16H2,1-5H3/t18-,19?,20+,21+,22+,23+,26-,27-/m1/s1

Upstream product

• 1060-51-1 3β-acetoxy-5β-cholestan-6-one 
• 75676-29-8 3β-acetoxy-6-fluorocholest-5-ene 

Relevant academic research and scientific papers

Effects of novel synthetic sterol probes on enzymes of cholesterol metabolism in cell-free and cellular systems

A series of novel sterols was synthesised as probes for the enzymatic and cellular functions of two important enzymes of intracellular cholesterol metabolism, acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol 7α-hydroxylase. The compounds were 6-fluoro-5-cholesten-3β-ol (6-fluorocholesterol), 7-cholesten-3β-ol (7-cholestenol), 6β-fluorocholestan-3β-ol (6β-fluorocholestanol), 3-acetoxy-6-fluorocholestan-3β-ol (3-acetoxy-6-fluorocholestanol) and 7-methoxy-5-cholesten-3β-ol (7-methoxycholesterol). They were designed to reveal the effect of small changes in sterol structure, particularly reactivity of certain parts of the ring structure and polarity, on enzyme activity and intracellular cholesterol metabolism. The 3β-hydroxy group was essential for interaction with both enzymes since 3-acetoxy-6-fluorocholestanol did not affect any of the enzyme-catalysed reactions. 6-Fluorocholesterol and 7-cholestenol had no effect on cholesterol esterification but did inhibit the hydroxylation of cholesterol, as did the other compounds with groups that could influence the 7 position, namely 6β-fluorocholestanol and 7-methoxycholesterol. The fluorocholestanols were all competitive substrates for cholesterol esterification in cell-free and cellular assays of ACAT activity. 7-Methoxycholesterol was a surprisingly effective inhibitor of ACAT for a simple sterol. However, 6-fluorocholesterol did not have any effect on ACAT, suggesting that interactions between the enzyme and the region around C-6 and C-7 of the sterol are important. These results show that it is possible to dissect components of cholesterol metabolism using simple, specifically substituted sterols and thus define a new approach to studying the relationships between the various enzymes that catalyse intracellular cholesterol metabolism.

Orientation of fluorinated cholesterol in lipid bilayers analyzed by 19F tensor calculation and solid-state NMR

6-F-cholesterol was reported to exhibit biological and interfacial properties similar to unmodified cholesterol. We have also found that 6-F-cholesterol mimicked the cholesterol activity observed in the systems of amphotericin B and lipid rafts. However, to use 6-F-cholesterol as a molecular probe to explore molecular recognition in membranes, it is indispensable to have detailed knowledge of the dynamic and orientation properties of the molecule in membrane environments. In this paper, we present the molecular orientation of 6-F-cholesterol (30 mol %) in dimyristoylphosphatidylcholine (DMPC) bilayers revealed by combined use of 19F chemical shift anisotropy (CSA), 2H NMR, and C-F rotational echo double resonance (REDOR) experiments. The axis of rotation of 6-F-cholesterol was shown to be in a similar direction to that of cholesterol in DMPC bilayers, which is almost parallel to the long axis of the molecular frame. The molecular order parameter of 6-F-cholesterol was determined to be ca. 0.85, which is within the range of reported values of cholesterol. These findings suggest that the dynamic properties of 6-F-cholesterol in DMPC are quite similar to those of unmodified cholesterol; therefore, the introduction of a fluorine atom at C6 has virtually no effect on cholesterol dynamics in membranes. In addition, this study demonstrates the practical utility of theoretical calculations for determining the 19F CSA principal axes, which would be extremely difficult to obtain experimentally. The combined use of quantum calculations and solid-state 19F NMR will make it possible to apply the orientation information of 19F CSA tensors to membrane systems.

Preparation of vinylene fluorides

A ketone is reacted with an N,N-disubstituted-aminosulfur trifluoride in the presence of a polar solvent, preferably also in the presence of a polar catalyst, to produce a vinylene fluoride. Exemplary is the reaction of cholestan-3β-ol-6-one-3-t-butyl ether with diethylaminosulfur trifluoride in the presence of fuming sulfuric acid and tetrahydrofuran to produce 6-fluorocholesterol.