Synthesis Study Of A Key Intermediate Of Atorvastatin Calcium Side-chain And Chiral Separation Of β-amino Acid Derivatives By HPLC

The paper was focused on the synthesis of key intermediate for atorvastatin calcium and chiral separation ofβ-amino-α-hydroxy acid derivatives by HPLC.Atorvastatin calcium is a new type of hypolipidemic drugs-statin drugs,which has extreme efficacy with little side-effect,and won a dominant position in the hypolipidemic drugs market,meanwhile has the highest growth rate leapt to the forefront in the entire cardiovascular drugs market.Generally,statin drugs are synthesized by the clustering approaches,that is, firstly the main skeleton and hexanoate with double chiral hydroxy group are synthesized separately,and then gain the final product.by condensation reaction. There are various approaches to synthesize the crucial intermediates.Therein,we take times on the synthesis of 4-chloromethyl-6-iodomethyl-2,2-dimethyl-[1,3]dioxane,by which other statins intermediates can prepare.By doing research on the literature reports,we are groping for a innovational route:use the low-cost(R)-epichlorohydrin as the starting material and gain the product by epoxy ring-opening,iodolactonization and hydroxyl protection.Compared with other ways,this method avoids the pollution of heavy metals and can be very good to maintain the first chiral center.Another part is the separation ofβ-amino acid derivatives enantiomers by high-performance of chromatography(HPLC) using chiral chroamtafraphy. Particularly in the past 20 years,optical resolution by HPLC has progressed rapidly, and has become a practical and useful method fordetermining optical purity.In this paper,we use the chiral IA column to explore the optimal conditions.The influence of the alcohol in mobile phase,pH modifier and flow of the mobile phase was studied. The ultimate condition can be used to separate variesβ-amino acid derivatives in relatively short period.