George J. Schroepfer Jr. Pages 103 - 120 ( 18 )
3β-Hydroxy-5α-cholest-8(14)-en-15-one is an oxysterol which shows high potency in the inhibition of sterol synthesis and in the suppression of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in mammalian cells. The 15-ketosterol, which shows significant hypocholesterolemic activity upon oral administration to animals, has been the subject of intensive investigation over the past two decades. Considerations of the metabolism of the 15-ketosterol have provided the basis for the rational design of improved analogs. The construction of these analogs was facilitated by the development of a highly efficient and specific method for the oxidative cleavage of the side chain Δ8(04)-15- ketosterols to give synthons from which the new analogs could be prepared. Apart from their increased potencies with regard to lowering of serum cholesterol levels, the new analogs of the 15-ketosterol display other favorable features.