Asymmetric synthesis of alpha-amino acids using a chiral catalyst

Mani Subramanian Iyer, Purdue University

Abstract

The Strecker amino acid synthesis is a flexible, general strategy for the synthesis of $\alpha$-amino acids that has proved exceptionally valuable. A novel cyclic dipeptide has been prepared which catalyzes an enantioselective version of the Strecker synthesis, is composed of (S)-phenylalanine and the non-proteinogenic $\alpha$-amino acid (S)-$\alpha$-amino-$\gamma$-guanidinobutyric acid, the lower homologue of (S)-arginine, prepared from (S)-glutamic acid by Curtius rearrangement. Because 2-aminophenylacetonitrile, the precursor to phenylglycine, proved not to be configurationally stable at 25$\sp\circ,$ a variety of N-alkyl-$\alpha$-amino nitriles was examined for suitability as intermediates. While all the substituted imines afforded the corresponding $\alpha$-amino nitriles in high yield and high enantiomeric excess, N-benzhydryl imines proved to be the substrates of choice as the benzhydryl group was cleaved during acid hydrolysis of the nitrile to afford the corresponding $\alpha$-amino acids directly. This methodology was applied to a series of N-benzhydryl imines; while those derived from aromatic aldehydes afforded (S)-$\alpha$-amino nitriles in generally high yield and enantiomeric excess, reaction of imines derived from aliphatic aldehydes proceeded in lower yield and low enantiomeric excess. This method can be used to obtain arylglycines, a class of $\alpha$-amino acids that is difficult to synthesize by many other methodology.

Degree

Ph.D.

Advisors

Lipton, Purdue University.

Subject Area

Organic chemistry

COinS