Semi synthetic statins (simvastatin) derived from lovastatin

A process has been provided to produce semi-synthetic statins defined as Formula I. It is known that certain mevalonate derivatives are active as hypercholesterolemic agents, which function by limiting cholesterol biosynthesis by inhibiting the enzyme HMG-CoA reductase. These mevalonate derivatives are natural occurring fungal metabolites lovastatin and compactin. The process provides for the precursor lovastatin contaminated with dihydrolovastatin to be converted to simvastatin. The naturally occurring compound lovastatin and compactin possess a 2-methylbutyrate side chain in the 8-position of the hexahydronaphtalene ring system. Analogs with a 2,2-dimethylbutyrate moiety in this position, such as simvastatin, appeared to be more effective inhibitors of HMG-CoA reductase. There are two possible routes for the introduction of an extra a-methyl group in the 8-acyl side chain which are: 1. direct alkylation of the 2 methylbutyrate side chain 2. removal of the 2-methylbutyrate side chain and introduction of a 2,2-dimethyl butyrate chain. The constituents of Formula I are as follows: R1 and R2 selected from H, OH, C1-10alkyl and C6-14aryl and C6-14arylC1-3alkyl; R3 is R9-C=O or hydrogen; R9, R4 and R5 are: 1. C1-15 alkyl 2. C3-15cycloalkyl 3. C2-15 alkenyl 4. C2-15alkynyl 5. Phenyl 6. PhenylC1-6alkyl R9 may also be halogen, C1-6alkyl, C1-6alkoxy and C6-14aryl R4 and R5 may also be 5, 6 or 7 membered heterocycle moiety such as pyrrolidine, piperidine or a homopiperidine R6 and R7 are selected from: 1. dioxane moiety 2. cyclic sulfate 3. cyclic phosphate