Atorvastatin Intermediates ATS-8

Although L-tert-leucine is not a protein-derived amino acid, because the structure of tert-butyl is very close to amino and carboxyl groups in space, the peptide bond of L-tert-leucine is designed to be slowly hydrolyzed by proteases in the body, so it contains this Substances and derivative drugs are part of modern new drug development

The key to the preparation of N-methoxycarbonyl-L-tert-leucine is to obtain chiral pure L-tert-leucine. The preparation methods of L-tert-leucine can be divided into two types: resolution method and asymmetric synthesis method.

The resolving agent used in the chemical resolution method is diphthalate tartaric acid, quinine or quinine. Biological enzymes can also be used for resolution due to their high selectivity, but only L-type tert-leucine can be obtained. The described method has a common shortcoming that it is necessary to prepare racemic tert-leucine first, and then derivatize it, and then use the corresponding resolving agent or enzyme to split it, which is relatively expensive and often has low purity. Moreover, the yield of a single configuration prepared by the resolution method is often less than 50%.

Chiral asymmetric synthesis is a relatively direct and purposeful synthesis of chiral target compounds. Tert-leucine is a type of α-amino acid. For α-amino acids, the classic chemical synthesis method is Strecker reaction, which uses cyano group The asymmetric addition to imines builds the stereochemistry of the product, and then undergoes hydrolysis and other reactions to prepare α-amino acids. During the reaction, adding ligand or Lewis acid can obtain higher selectivity. However, the disadvantage of the Strecker reaction is that it is not easy to realize mass production and preparation, and the toxicity of cyano groups is also relatively large, which causes serious environmental pollution. Biological enzymatic conversion of latent chiral compounds to prepare amino acids not only has mild reaction conditions, high yield and optical purity, but also avoids pollution problems caused by chemical synthesis, and has great application potential and broad development prospects.