Sterols affecting meiosis: novel chemical syntheses and the biological activity and spectral properties of the synthetic sterols.
J Lipid Res 1998 Oct;39(10):2005-20
4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol (I) from human follicular fluid and 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-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 delta8(14),24 analog XXII. A critical step in these syntheses was a remarkably high yield side chain oxidation of 3beta-acetoxy-4,4-dimethyl-5alpha-cholest-8(14)-en-15-one to the corresponding C24 24-hydroxy compound VI. Oxidation of VI to the aldehyde, followed by Wittig olefination gave 3beta -acetoxy4,4-dimethyl-5alpha-cholesta-8(14),24-dien-15- one. Reduction with sodium borohydride to the 15beta-hydroxysteryl ester, dehydration with sulfuric acid in CHCl3, and saponification furnished I in high purity. Reduction of VI with sodium borohydride to the 15-hydroxysteroid followed by dehydration gave 3beta-acetoxy-4,4-dimethyl-5alpha-chola-8,14-dien-24-o l. Hydrogenation over Raney nickel gave the monounsaturated delta8(14) and delta8 compounds. Oxidation to the corresponding aldehydes followed by Wittig olefination and saponification gave II and XXII. Chromatographic, mass spectral, and 1H and 13C nuclear magnetic resonance spectral data have been presented for the synthetic sterols and their derivatives. I, II, XXII, and their delta8,14 and delta7,14 analogs, at 3 microg per ml, caused a resumption of meiosis in mouse oocytes in the presence of hypoxanthine (3.5 mM). Under the same conditions, delta5 and delta5,7 sterols were inactive.
Ruan, B; Watanabe, S; Eppig, J J.; Kwoh, C; Dzidic, N; Pang, J; Wilson, W K.; and Schroepfer, G J., " Sterols affecting meiosis: novel chemical syntheses and the biological activity and spectral properties of the synthetic sterols." (1998). Faculty Research 1990 - 1999. 1137.