BOC Sciences is committed to providing effective and reliable amino acid asymmetric alkylation synthesis strategies to meet the different needs of customers.
Amino acids are the basis of peptide and protein synthesis, play an important role in the reaction process of oxidation, reduction, hydrolysis and carbon-carbon bond formation in vivo, and determine the properties of peptides and proteins. Among them, optically active amino acids and their derivatives have a wide range of uses in physiology and pharmacology, which has aroused great research enthusiasm of scientists, and methods for asymmetrically synthesizing optically pure amino acids continue to emerge.
Asymmetric alkylation is an asymmetric synthesis in the form of an alkylation reaction. Asymmetric alkylation of amino acids has important applications in medicine, biochemistry, protein and genetic engineering. We use the asymmetric alkylation reaction strategy to realize the efficient synthesis of optically active amino acids, which provides an important tool for the synthesis of active natural products, functionalized peptides and proteins, and the study of the reaction mechanism of biologically active substances.
Various chiral auxiliary agents, such as oxazolidinone, thiazolethione, camphorsultam, prolinol, oxazolidine-2-phenylamine, etc., are widely used to induce asymmetric alkylation reactions, showed a good inducing effect. We use chiral auxiliaries to induce electrophilic substitution reactions of reaction substrates to form carbon-carbon bonds to synthesize optically pure amino acids. Most of the electrophilic reagents are halogenated hydrocarbons (iodohydrocarbons, bromohydrocarbons, chlorinated hydrocarbons), aldehydes, ketones, etc.
Steps for asymmetric synthesis using chiral auxiliaries
We synthesized optically pure α-substituted amino acids by forming Schiff bases to activate carbon-hydrogen bonds. If the aldehyde or ketone group is connected to a chiral group, the α-position substitution of the α-amino acid will be induced by the chiral group and have certain enantioselectivity.
Phase transfer catalysis is characterized by mild reaction conditions, simple operation, and cost-effectiveness. We use phase transfer catalysis for the asymmetric alkylation of amino acids to synthesize various unnatural amino acids. With α-amino acids and their derivatives as substrates, α-hydrogen protons are removed under alkaline conditions. An alkyl group is then introduced on the α-carbon of the amino acid by an electrophilic substitution reaction. The substrate and the base are placed between the two phases, and the proton exchange is assisted by a phase transfer catalyst. α-Amino acids and their derivatives can be prochiral, and a chiral environment can be provided by a chiral phase transfer catalyst or a chiral inducing group, so as to obtain certain enantiomeric excess amino acids.
The Strecker reaction is particularly suitable for the synthesis of N-substituted α-amino acids. Chiral amines react with aldehydes or ketones to form Schiff bases containing chiral auxiliary groups, which are widely used as precursors of chiral α-amino acids, and can be used for the synthesis of chiral α-amino acids after Strecker reactions. Commonly used chiral amines include α-phenylethylamine, β-amino alcohol and its derivatives, etc.
The Mannich reaction can be used for the synthesis of chiral α-amino acid and β-amino acid derivatives. The Mannich reaction of glycine Schiff base and imine can be used to synthesize chiral α, β-diamino-substituted amino acids and their derivatives.