Synthesis of cholesterol‐20‐¹⁴C

Abstract

SUMMARYCholester01-20-~4C was synthesized in four steps from pregneno10ne-20-~~C. The labelled intermediates were proven to be cholest-5-ene-jp, 2Ou-diol acetate-3, cholesta-5, 20 (22)-diene-3/3-01 acetate, and cholesterol acetate by lH-n.m.r. spectroscopical analysis, Chole~teroL20-~~C was obtained with a radiochemical purity exceeding 99 %.In connection with our work on the biosynthesis of bufadienolides from animal and plant origin (l), it was required the preparation of cholestero1 labelled with 14C at any carbon-atom of the side chain but carbons 25, 26 and 27.Since pregnenolone-20-14C had been previously synthesized (2) we chose this labelled steroid as starting material for the preparation of cholesterol labelled with 14C at C-20.When pregnenolone-20-14C acetate (I) was treated with the Grignard reagent prepared from isohexyl bromide (3), cholest-5-ene-3P, 201x-dio1-20-~~C acetate-3 (11) was obtained in good yield. This compound was first synthesized by Petrow and Stuart-Webb (4) although at that time the authors did not disclosed the stereochemistry of the product. The same method was utilized later by Bergman et al. The labelled 20-hydroxy-cholesterol (11), without purification, was dehydrated by reaction with POCl, and pyridine in a sealed tube (') to cholesta-5, 20 (22)-diene-3P-ol-20J4C acetate (111). It seemed reasonable to suppose that * Research Member of the Consejo Nacional de Investigaciones Cientificas y Tknicas-

Acétate de nor-24 cholestéryle

“…Un de nos laboratoires l'a obtenu par r~action de Grignard ou de Wittig sur la pregn~nolone et aussi par reaction de Grignard sur l'acide hydroxy-3fl bisnor-22,23 A 5 chol~nique (Evrard, Denayer-Tournay, Wilpart & Piraux, 1979). Cette derni~re approche pr6sente, sur les deux pr6c6dentes, l'avantage d'une certitude absolue au sujet de la configuration au niveau du carbone 20 du st~ro'/de; l'acc6s ~t la s6rie naturelle a toutefois 6t~ d~crit /t partir de la pregn~nolone (Porto & Gros, 1968;Ikan, Markus & Bergmann, 1971). La seule difficult~ & vaincre pour synth6tiser le nor-24 cholest6rol & partir de l'acide bisnor-chol6nique est le peu d'accessibilit6 de la position 22 de tout st6ro'/de (Cole & Julian, 1945).…”