Preparation Of P-Methyl-Phenylalanine

The dissertation is focused on the synthesis of an important unnatural amino acid p-methyl-phenylalanine. The synthetic route is very guidable to synthesize other unnatural amino acids, especially for other substituted phenyl or heterocylic substituted alpha alanines.Based on the chemical structure of p-methyl-phenylalanine, we utilized the disconnection method via retrosynthetic analysis to compare several possible routes as well as reaction conditions with the reported literatures. A novel possible route was proposed and established, starting from 1-(chloromethyl)-4-methyl benzene and diethyl malonate via alkylation, hydrolysis, cyclization, ammonation, Hofman degradation, with an overall yield of 24-25%. The synthetic route has several advantages, such as commercially available and cheap raw materials, no heavy metal reagents or highly poisonous chemicals involved. Moreover, all separation operations are not required to column chromatography, large potential to scale up for industrialization, promising to get independent intellectual property rights.