Amino Acids for Chiral Drug

Introduction

Amino acids are the basic building blocks of proteins and play an important role in life activities. The importance of chiral drugs in the field of drug development cannot be underestimated. In the pharmaceutical industry, most drugs are chiral drugs, and all use chiral amino acids and their derivatives (such as chiral amines, chiral amino alcohols) as the core structural units. Chiral amino acids are widely used in medicine, pesticides, fine chemicals, materials and other fields.

For chiral amino acid drugs, it is necessary to study the differences in pharmacological activity, absorption, distribution, metabolism and excretion between them and enantiomeric drugs, as well as the correlation between their structure and configuration and biological activity, pharmacodynamics, metabolism and toxicity.

• For Chiral Synthesis

The synthetic methods of chiral amino acids include chemical resolution, asymmetric synthesis, crystallization, microorganisms, enzymes, coordination extraction, membrane separation, and chromatography. Asymmetric synthesis and enzymatic methods are the main chiral amino acid synthesis methods. Asymmetric synthesis is very important in organic synthesis, especially in the synthesis of chiral drugs. Compared with other methods, the advantages of enzymatic method are high conversion rate, usually carried out in natural environment, mild reaction conditions and less pollution.

• For Chiral Resolution

The research and development of chiral drugs has become an important direction and hot field of new drug research and development. Most of the current drugs are in the form of racemates, that is, the drugs contain equal amounts of the left and right enantiomers. However, the single-enantiomer drug market is gradually growing every year. The racemate resolution method is to separate the racemate into two enantiomers by physical, chemical or biological methods under the action of a resolving agent. As a classic separation method, the racemate separation method has the advantage of saving time and has been widely used in industrial production. The racemate resolution method can be divided into crystallization resolution, chemical resolution, biological resolution, chromatographic resolution, membrane resolution and chiral extraction resolution.

• For Chiral Analysis

With the deepening of the research on the pharmacological activities of chiral drugs, researchers have recognized and paid attention to the differences in the physiological effects and metabolic processes of chiral drug enantiomers. Modern separation and analysis techniques have shown great advantages in the separation and determination of enantiomers. Commonly used analytical techniques for chiral drugs include high performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC), capillary electrophoresis (CE), and the like. These chiral chromatographic techniques combine separation and analysis to enable rapid characterization, quantitative analysis of enantiomers and even small preparations.

The HPLC method introduces an asymmetric center to achieve the separation of enantiomers, which is divided into indirect method and direct method. GC method is an earlier method used for enantiomeric separation analysis. For volatile, thermally stable chiral molecules, this method shows clear advantages. The SFC method combines the advantages of HPLC and GC, and can be analyzed using various detectors of HPLC and GC. The CE method provides an economical and effective means for the separation of chiral drugs with high polarity, poor thermal stability and volatile volatility.

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