Synthesis of zymosterol, fecosterol, and related biosynthetic sterol intermediates

Article abstract of DOI:10.1021/ja00183a042

The first syntheses of sterol biosynthetic intermediates zymosterol(4), 4,4-dimethylzymosterol(5), cholesta-8,14,24-trien-3β-ol(6), the 4,4-dimethyl analogue 7, and fecosterol (8) are described in detail. Multigram quantities of key intermediates 16 and 17 were efficiently prepared from known enones 20 and 21 (eight steps, 35% overall yield). Novel entry into Δ⁸-sterols was achieved through regiospecific hydroboration/deoxygenation of the 8,14-diene systems. Sterols containing Δ²⁴- or Δ(24(28))-olefins were obtained from C24-hydroxy intermediates either via dehydration using bis[α,α-bis(trifluoromethyl)benzenemethanolato]diphenylsulfur in CH₂Cl₂ or via Swern oxidation/Wittig olefination, respectively. In this way, 16 and 17 were converted to the desired Δ^8,24-, Δ^8,14,24-, and Δ(8,24(28))-sterols with high regiocontrol.