Synthetic Methods for Simvastatin – an Overview

Document Type : Original Article


Research and Process Development, Sterling Biotech Limited, Jambusar State Highway, Vadodara, Gujarat-391421, India



There are three basic methodologies for simvastatin production; biosynthesis or the fermentation technology
method using fungal stains, biocatalytic method to convert lovastatin into simvastatin and synthetic methods for
modification of lovastatin into simvastatin. Out of all three methodologies, synthetic modifications of lovastatin into
simvastatin are commercialized and widely used methodologies. There are two possible synthetic routes for simvastatin;
direct alkylation route and re-esterification route. Relatively high yield and fewer synthetic steps are the main advantages
of adopting direct alkylation route while re-esterification route, wherein the 2-methyl butyrate side chain is completely
removed and 2,2-dimethylbutyrate side chain is introduced, gives better quality of simvastatin, as the separation of the
hydrolyzed product and the esterified product is much easier to achieve compared to the unreacted starting material and the
methylated product.