Iso-Simvastatin-6-one

A simple two step synthesis of the 3'(S)-hydroxylated derivative of simvastatin, I, isolated from rat and mice liver microsomes along with the 3'(R) epimer and a two step preparation of the 3'(S)-5'(S)-dihydroxylated compound is described.

Autoxidation of the cholesterol-lowering agent simvastatin in ethylene dichloride solution with an azo-type free-radical initiator was investigated in kinetic studies using HPLC.The primary products were oligomers, with peroxide groups within the backbone chain, and some monomeric epoxides.These and several secondary products were isolated chromatog. and identified spectroscopically.A reaction scheme was proposed in which the oligomers arise from competitive hydrogen abstraction and addition reactions of oligomeric free radicals with simvastatin while the epoxides arise from homolytic peroxide cleavage.