SYNTHESIS OF 4-ALPHA-(2-PROPENYL)-5,6-SECOCHOLESTAN-3-ALPHA-OL, A NOVEL B-RING SECO ANALOG OF THE HYPOCHOLESTEROLEMIC AGENT 4-ALPHA-(2-PROPENYL)-5-ALPHA-CHOLESTAN-3-ALPHA-OL

4 alpha-(2-Propenyl)-5 alpha-cholestan-3 alpha-ol (LY295427) Ir as pre viously identified front a CHO cell-based assay to be a potent LDL rec eptor up-regulator and had demonstrated to be an effective agent in lo wering plasma cholesterol levels in hypercholesterolemic hamsters. In order to investigate the effect of flexibility of the 3 alpha-hydroxy- bearing A-ring on the activity 4 alpha-(2-propenyl)-5,6-secocholestan- 3 alpha-ol (II), a B-ring seco analog of LY295427, is thus synthesized from cholest-4-en-3-one. Test results indicate that II is not active in the CHO cell-based LDL receptor/luciferase assay at concentrations rip to 20 mu g/mL. The result underlines the importance of maintaining the A-B-C-D ring rigidity of the 3 alpha-sterols in terms of binding to the putative oxysterol receptor. (C) 1998 by Elsevier Science Inc.