STEROLS AFFECTING MEIOSIS - NOVEL CHEMICAL SYNTHESES AND THE BIOLOGICAL-ACTIVITY AND SPECTRAL PROPERTIES OF THE SYNTHETIC STEROLS

4,4-Dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol (I) from human f ollicular fluid and 4,4-dimethyl-5 alpha-cholesta-8,24-dien-3 beta-ol (II) from bull testes have been reported to activate meiosis in mouse oocytes (Byskov et al,, 1995, Nature. 374: 559-562), Described herein are new chemical syntheses of I, II, and the Delta(8(14),24) analog XX II, A critical step in these syntheses was a remarkably high yield sid e chain oxidation of 3 beta-acetoxy-4,4-dimethyl-5 alpha-cholest-8(14) -en-15-one to the corresponding C-24 24-hydroxy compound VI, Oxidation of VI to the aldehyde, followed by Wittig olefination gave 3 beta-ace toxy-4,4-dimethyl-5 alpha-cholesta-8(14),24-dien-15-one, Reduction wit h sodium borohydride to the 15 beta-hydroxysteryl ester, dehydration w ith sulfuric acid in CHCl3, and saponification furnished I in high pur ity. Reduction of VI with sodium borohydride to the 15-hydroxysteroid followed by dehydration gave 3 beta-acetoxy-4,4-dimethyl-5 alpha-chola -8,14-dien-24-ol. Hydrogenation over Raney nickel gave the monounsatur ated Delta(8(14)) and Delta(8) compounds, Oxidation to the correspondi ng aldehydes followed by Wittig olefination and saponification gave II and XXII, Chromatographic, mass spectral, and H-1 and C-13 nuclear ma gnetic resonance spectral data have been presented for the synthetic s terols and their derivatives. I, II, XXII, and their Delta(8,14) and D elta(7,14) analogs, at 3 mu g per mi, caused a resumption of meiosis i n mouse oocytes in the presence of hypoxanthine (3.5 mM). Under the sa me conditions, Delta(5) and Delta(5,7) sterols were inactive.