Recent Advances in the Synthesis and Analysis of Atorvastatin and its Intermediates

Shu-Fang Li; Wei Zhang; Wen Zhang; An Huang; Jia-Qi Zhu; Ya-Jun Wang; Yu-Guo Zheng

doi:10.2174/0109298673263728231004053704

Recent Advances in the Synthesis and Analysis of Atorvastatin and its Intermediates

Curr Med Chem. 2023 Oct 11. doi: 10.2174/0109298673263728231004053704. Online ahead of print.

Authors

Shu-Fang Li^{1

2

3}, Wei Zhang^{1

2

2}, Wen Zhang^{1

2

3}, An Huang^{1

2

3}, Jia-Qi Zhu^{1

2

3}, Ya-Jun Wang^{1

2

3}, Yu-Guo Zheng^{1

2

3}

Affiliations

¹ Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P.R. China.
² Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P.R. China.
³ The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P.R. China.

PMID: 37828675
DOI: 10.2174/0109298673263728231004053704

Abstract

Atorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations.

Keywords: 5R)-dihydroxyheptanoate; Atorvastatin; Paal-Knorr synthesis; impurity; side chain; synthetic route; tert-butyl (3R.