Towards a New Type of HMG-CoA Reductase Inhibitors: Part II: Dramatic Substituent Effects in the C-5 Epimerisation of Carbohydrate Derivatives

Article abstract of DOI:10.1016/S0040-4020(01)80508-1

In the course of our search for a new class of HMG-CoA reductase inhibitors, the synthesis of reaction intermediate analogues was investigated.Compound 2, having the C-5 (R) configuration of natural mevinic acids, was prepared in enantiomerically pure form starting from levoglucosan.During this synthesis, an epimerisation of the olefinic intermediate 16 was observed and was found to depend strongly both on the axial or equtorial orientation and on the nature of the C-3 substituent.Biological activity of compound 2 is reported.Keywords: HMGCoA reductase, inhibitor, carbohydrate, base catalyzed epimerisation, O-silyl protecting group.