Synthesis of trans-(3R,5S)-Atorvastatin Ca and Curative Effect on Hyperlipidemia Induced by a High-Fat Diet in Rats

Abstract

요 약 고지혈증 치료제인 cis-(3R,5R)-atorvastatinAbstract cis-(3R,5R)-Atorvastatin Ca (1) used for hyperlipidemia have four stereomers. However, It is very difficult to prepare stereoselective stereomers. In this paper, the reduction of 3,5-diketo atorvastatin ester (3) was performed using Me4NHB(OAc)3 in acetic acid as a reductant and showed excellent stereoselectivity in the double reduction of 3,5-diketo atorvastatin ester (3). As a result, reduction of compound 3 by Me4NHB(OAc)3 was purely obtained with cis-(3R,5R)-atorvastatin ester (4) of 1.5% and trans-(3R,5S)-atorvastatin ester (5) of 98.5%. Also, cis-(3R,5R)-atorvastatin Ca (1) and trans-(3R,5S)-atorvastatin Ca (7) were used to determine efficacy in the treatment of liver damage and hyperlipidemia induced by a high-fat diet in rats and to study the performance of the January 2010 experient was conducted. As a result, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels of compound 1 and 7 groups were 93.0±0.5, 43.5±0.8, 40.4±1.4, 45.6±0.9 mg/㎗ and 110.0±0.7, 33.3±0.6, 65.8±1.9, 54.8±1.2 mg/㎗, respectively. Atherogenic index (AI) and cardiac risk factor (CRF) in compound 1 and 7 were 1.14±0.05, 2.14±0.05 and 2.31±0.06, 3.31±0.06, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 51.9±4.6, 16.0±2.1 IU/ℓ and 75.8±4.4, 35.1±9.7 IU/ℓ. Taken together, while compound 1 treat against high-fat diet-induced hyperlipidemia by attenuating hepatic lipid depots and reducing oxidative stress, compound 7 group had a low curative effect on hyperlipidemia induced by a high-fat diet in rats. These findings suggest that new method about synthesis of stereoselective stereomers and indicate that it may consider using in a clinical trial.