A one step procedure for the prcparation of labeled mevinolin analogs LQ and fi possessing the 2,2-dimethylbutyryloxy side chain is described. The lactones L I and 12 were converted into potassium salts of their corresponding d i or trihydroxy c boxylic acids from which anionic ester enolates were generated and alkylated with [ Clmethyl iodide. Workup and purification by reverse phase HPLC provided radiochemically pure & Ip and fi. The labcled lactones were converted into ammonium salts of thcir corresponding d i or trihydroxy acids. M Key Words: HMG-CoA reductase inhibitors, [14C]Me.thylation of anionic ester enolates. Mevinolin analogs. INTRODUCTlON Mevinolin is G well known potent HMG-CoA reductase inhibitor. Related compounds possessing the 2,2-dimethylbutyryloxy side chain (& LQ, J5) are highly active inhibitors of HMG-CoA reductase and thus may have potential utility in the treatment of atherosclcrosis, hyperlipemia, familial hypercholesterolemia and like disorders.' For studies concerning metabolism and tissue distribution of these compounds in experimental animals. carbon-I4 labeled tracers were required. We report herein the prcparation of three such tracers.
The currently accepted generic name for "mevinolin" is "lovastatin". 0362-4803/88/080815-11505.50 0 1988 by John Wdcy & Sons. Lcd.