Preparation method of beta-homoglutamic acid

Abstract

The invention belongs to the field of preparation of organic compounds, and provides a preparation method of beta-homoglutamic acid. The method is characterized in that: 3-cyclohexenecarboxylic acid is used as a raw material, beta-homoglutamic acid is synthesized at a high yield through three the steps of reactions of Curtius rearrangement, olefin oxidation and protection group removal, and beta-homoglutamic acid with high yield and high optical purity can be obtained through configuration retention by using optically pure 3-cyclohexenecarboxylic acid. The method has the advantages of easily available raw materials, mild reaction conditions and low cost, and is suitable for large-scale preparation of beta-homoglutamic acid.

Description

technical field [0001] The invention belongs to the field of preparation of organic compounds. The invention relates to a method for preparing β-homoglutamic acid. Background technique [0002] β-homoglutamic acid is a very important non-natural β-amino acids. In recent years, it has been widely used in the synthesis of new peptide drugs and the development of nanomaterials, and the research on its synthesis methods has gradually been paid attention to. At present, there are two main strategies for preparing optically pure β-homoglutamic acid: one is to use optically pure chiral auxiliary reagents for chiral induction synthesis, such as the optically pure 2-tert-butylperhydropyrimidinone induction method reported by Snieckus (J.Am. Chem.Soc.1996,118,8727), the D-gulose derived hydroxylamine induction method developed by Bode (Chem.Sci.2010,1,637.), although this strategy can successfully prepare chiral β-homoglutamic acid A variety of β-amino acids, but the chiral inductio...

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Problems solved by technology

At present, there are two main strategies for preparing optically pure β-homoglutamic acid: one is to use optically pure chiral auxiliary reagents for chiral induction synthesis, such as the optically pure 2-tert-butylperhydropyrimidinone induction method reported by Snieckus (J.Am. Chem.Soc.1996,118,8727), the D-gulose derived hydroxylamine induction method developed by Bode (Chem.Sci.2010,1,637.), although this strategy can successfully prepare chiral β-homoglutamic acid A variety of β-amino acids, but the chiral induction reagent used in this method is not easy to obtain, the preparation is cumbersome, and the cost is high; another strategy is to use L-glutamic acid as the starting material to react with diazomethane at low temperature Synthesis of diazoketone and rearrangement to obtain β-homoglutamic acid (Tetrahedron 2000,56,9739; J.Org.Chem.1999,64,2176; J.Med.Chem.1990,33,2734.), the scheme Because the raw materials are easy to obtain, the cost is low, and the optical purity of the product is high, it is widely used. However, because it uses very dangerous diazomethane, it requires low temperature reaction and is not suitable for scale-up.

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