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R A Pascal

Publications and source records attributed to R A Pascal.

27 records · Page 2Linked to original sources
PubMed1980

15-Oxygenated sterols with the unnatural cis-C-D ring junction. Studies of the metabolism of 5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol and 5 alpha,14 beta-cholest-7-ene-3 beta,15 beta-diol.

Four 15-oxygenated sterols with the "unnatural" cis-C-D ring juncture have recently been shown to be potent inhibitors of sterol synthesis in animal cells in culture (Schroepfer, G.J., Jr., Parish, E.J., Chen, H.W., and Kandutsch, A.A. (1977) J. Biol. Chem. 252, 8975-8980; Schroepfer, G.J., Jr., Pascal, R.A., Jr., and Kandutsch, A.A. (1979) Biochem. Pharmacol. 28, 249-252). In the present study we have prepared two of these sterols, [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol and [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 beta-diol, in labeled form, 5 alpha,14 beta-Cholest-7-ene-3 beta, 15 alpha-diol, but not its 15 beta-hydroxy epimer, was shown to be efficiently converted to cholesterol in 10,000 x g supernatant fractions of liver homogenate preparations from both male and female rats. After incubation of [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol with these enzyme preparations a number of labeled products, in addition to cholesterol, were isolated and characterized. These included 5 alpha-cholesta-8,14-dien-3 beta-ol, cholesta-5,7-dien-3 beta-ol, 5 alpha-cholest-8-en-3 beta-ol, and 5 alpha-cholest-7-en-3 beta-ol. A scheme to account for the enzymatic formation of cholesterol and the other sterol precursors of cholesterol is presented.

Animals↗
PubMed1980

Sterol synthesis. Chemical synthesis of 5 alpha-cholest-7-en-3 beta, 14 alpha-diol.

Reported herein is the chemical synthesis of 5 alpha-cholest-7-en-3 beta, 14 alpha-diol by mild Wolff-Kishner reduction of 3 beta-acetoxy-8 alpha, 14 alpha-epoxy-5 alpha-cholestan-7-one. The preparation of 5 alpha-cholest-7-en-14 alpha-ol-3-one from 5 alpha is also described. These compounds were fully characterized by the results of infrared, nuclear magnetic resonance, and high and low resolution mass spectral studies.

Cholestanols↗
PubMed1980

Inhibition of sterol biosynthesis in animal cells by 14 alpha-hydroxymethyl sterols.

The chemical syntheses of a number of 14 alpha-hydroxymethyl sterols and 14 alpha -hydroxymethyl-15 alpha-hydroxysterols and their derivatives have been pursued to permit evaluation of their activity in the inhibition of sterol biosynthesis in animal cells in culture. Described herein are chemical syntheses of 7 alpha,8 slpha-epoxy-14 alpha-methyl-5 alpha-cholestan-3 beta,15 alpha-diol, 14 alpha-methyl-5 alpha-cholestan-3 beta,7 alpha,15 alpha-triol, 3 beta,15 alpha-diacetoxy-14 alpha-methyl-5 alpha-cholestan-7 alpha-ol, 3 beta,15 alpha-diacetoxy-7 alpha,32-epoxy-14 alpha-methyl-5 alpha-cholestane, 14 alpha-hydroxymethyl-5 alpha-cholest-6-en-3 beta,15 alpha-diol, 14 alpha-hydroxymethyl-5 alpha-cholest-7-en-3 beta,15 alpha-diol, 7 alpha,32-epoxy-14 alpha-methyl-5 alpha-cholestan-3 beta,15 alpha-diol, 14 alpha-hydroxymethyl-5 alpha-cholest-6-en-3-one, 14 alpha-hydroxymethyl-5 alpha-cholest-7-en-3-one, and 14 alpha-hydroxymethyl-5 alpha-cholets-7-en-15 alpha-ol-3-one. The effects of eight of the above compounds and of 14 alpha-hydroxymethyl-5 alpha-cholest-8-en-3 beta-ol, 14 alpha-hydroxymethyl-5 alpha-cholest-7-en-3 beta-ol, 14 alpha-hydroxymethyl-5 alpha-cholest-6-en-3 beta-ol, and 7 alpha,32-epoxy-14 alpha-methyl-5 alpha-cholestan-3 beta-ol on the synthesis of digitonin-precipitalbe sterols and on levels of HMG-CoA reductase activity in L cells and in primary cultures of fetal mouse liver cells have been investigated. All of the 14 alpha-hydroxymethyl sterols and 14 alpha-hydroxymethyl-15 alpha-hydroxysterols were found to be potent inhibitors of sterol synthesis and to reduce the levels of HMG-CoA reductase activity in these cells. Since hydroxylation of the 14 alpha-methyl group of 14 alpha-methyl sterol precursors of cholesterol can be considered as an obligatory step in the biosynthesis of cholesterol, the finding that 14 alpha-hydroxymethyl sterols are potent inhibitors of cholesterol biosynthesis and cause a reduction in the levels of HMG-CoA reductase activity raises the possibility that oxygenated sterol precursors of cholesterol, such as 14 alpha-hydroxymethyl sterols, may play an important role in the regulation of cholesterol synthesis and in the regulation of processes dependent upon mevalonate and sterol formation.

Animals↗
PubMed1979

Chemical synthesis of three 14 alpha-hydroxymethyl cholestenols.

Reported herein are chemical syntheses of 14 alpha-hydroxymethyl-5 alpha-cholest-8-en-3 beta-ol, 14 alpha-hydroxymethyl-5 alph-cholest-7-en-3 beta-ol, and 14 alpha-hydroxymethyl-5 alpha-cholest-6-en 3 beta-ol. These compounds were obtained in pure form after repeated medium-pressure column chromatography of the mixture obtained by treatment of 3 beta-acetoxy-7 alpha,32-epoxy-14 alpha-methyl-5 alpha-cholestane with pyridine hydrochloride in refluxing acetic anhydride followed by reduction with lithium aluminum hydride. The compounds were characterized by their chromatographic properties and by the results of infrared, optical rotation, nuclear magnetic resonance, and low and high resolution mass spectral studies.

Cholestenes↗