The Catalytic AsymmetricStrecker Reaction

Abstract

Alpha‐amino acids are important building blocks for proteins, peptides, and pharmaceuticals. Among a variety of methods to synthesize optically active alpha‐amino acids, the Strecker reaction is one of the simplest and most powerful. This reaction consists of three steps (1) condensation of an aldehyde or ketone with an amine to produce and imine, (2) nucleophilic attack of cyanide on the imine to produce and amino nitrile, and (3) hydrolysis of the amino nitrile to the corresponding alpha‐amino acid. These steps can be conducted in one pot. Conversion of the nitrile group to amide, amine, or aldehyde functionalities is also possible. The catalytic promotion and enantiocontrol of the cyanide addition to the imines is the main focus of the Strecker reaction. Therefore, isolated and purified imines are normally used as substrates. The catalyst turnover efficiency and enantioselectivity of this step are intimately related to the electronic and steric characteristics of the substrate imines, with nitrogen substituent greatly contributing to these factors. However, since optically active alpha‐amino acids are generally the synthetic target of the catalytic asymmetric Strecker reaction, the accessibilty of the starting imines and ease of final deprotection of the product are also important considerations. This chapter focuses on catalytic enantioselective Strecker and Reissert reactions.

A study on the induction of stereoselectivity in the Strecker synthesis of basic amino acid-derived α-amino nitriles

“…First, we studied the replacement of ZnCl 2 by chiral organocatalysts in the synthesis of 9a. Among the diverse organocatalysts developed for enantioselective Strecker reactions, 6,8,11,12 we tried the commercial thiourea 12 ( Fig. 1), developed by the Jacobsen group.…”

“…[2][3][4] During the last years, attention has mainly been focused on the stereocontrol in the Strecker reaction, by using chiral auxiliaries 2,3,5,6 and, more recently, chiral catalysts. [5][6][7][8][9][10][11][12] -Amino nitriles are versatile intermediates for the synthesis of multiple building blocks. 5,6 In particular, -amino acid-derived amino nitriles have shown high potential for molecular diversity generation.…”

At the very beginning of life on Earth: the thiol-rich peptide (TRP) world hypothesis

“…In the case of amino acids, it is possible that some physical factors created a slight excess of the L-form (but it could have been D), for example during partial crystallization (Kojo et al, 2004) or sublimation (Fletcher et al, chains, would have favor the synthesis of homochiral peptides. It may be envisaged that this necessitated the implementation of asymmetric Strecker synthesis (Shibasaki et al, 2008).…”

Biotechnology in the Production of Pharmaceutical Industry Ingredients: Amino Acids

“…the process includes condensation of the aldehyde with ammonium chloride in the presence of potassium cyanide, forming an α-aminonitrile, which is then hydrolyzed to obtain the desired amino acid. the original Strecker reaction combines acetaldehyde, ammonia, and hydrogen cyanide to give alanine after hydrolysis (13,30,54). In the traditional synthesis of Adolph Strecker from 1850, racemic α-amino nitriles are formed, but several protocols employing asymmetric catalysts or auxiliaries have been developed since (15,26,29).…”