Synthetic method of D-heterocyclic amino acid, kit and application

Abstract

The invention provides a synthetic method of D-heterocyclic amino acid, a kit and an application. The synthetic method comprises the step that a keto acid compound of D-heterocycles is transformed into D-heterocyclic amino acid by diaminopimelic acid dehydrogenase shown as SEQ ID NO:1. The keto acid compound of D-heterocycles is transformed into D-heterocyclic amino acid by diaminopimelic acid dehydrogenase, so that non-natural chiral amino acid with higher transformation rate and higher ee can be obtained, the synthetic method based on diaminopimelic acid dehydrogenase adopts stable technological conditions and mild reaction conditions, the whole production process is simple to operate, less pollution is produced, and one new way of thinking is provided for artificial synthesis of D-heterocyclic amino acid.

Description

technical field [0001] The invention relates to the field of synthesis of unnatural amino acids, in particular to a synthesis method, kit and application of a D-heterocyclic amino acid. Background technique [0002] Unnatural chiral amino acids and their derivatives are important constituent units of polypeptides, peptoids and many drug molecules, and are also key intermediates for the synthesis of chiral drugs. At present, the synthesis of chiral non-natural heterocyclic amino acids mainly adopts chemical methods, including the use of noble metal asymmetric catalytic hydrogenation to realize the conversion of a single configuration of a key intermediate, the use of chiral reagents to resolve racemates, Asymmetric synthesis using chiral prosthetic groups, directional synthesis using chiral raw materials, etc. However, these methods have the following disadvantages: 1) use precious metal asymmetric catalytic hydrogenation to realize the transformation of a single configurati...

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Problems solved by technology

However, these methods have the following disadvantages: 1) use precious metal asymmetric catalytic hydrogenation to realize the transformation of a single configuration of a key intermediate, the disadvantage is that the noble metal asymmetric catalyst is expensive, the reaction requires a large amount of organic solvent, and the product contains Heavy metal residues and over-reduced by-products may exist, and because the synthetic raw materials contain heterocycles, they often interfere with the combination of noble metals and ligands, resulting in low catalytic efficiency; 2) Using traditional chiral resolution methods, the obtained An isomer in the racemate will cause additional waste of raw materials; 3) the asymmetric synthesis of chiral prosthetic groups or chiral raw materials involves expensive chiral raw materials, long synthetic routes and a large number of Organic solvents, and for the synthesis of some heterocyclic amino acids, the optical purity of the obtained product is not high, or the product and impurities are not easy to separate

However, due to the special properties of heterocyclic amino acids, there are the following problems in the production of chiral unnatural amino acids by chemical methods in the prior art: chiral metal catalysts are generally required, the synthesis route is long, the use of a large amount of organic reagents causes serious environmental pollution, and the production cost High and the optical purity of the product is difficult to meet the requirements

There is no suitable report on the synthesis of amino acids with D-heterocyclic structure through the biotransformation of biological enzymes

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