Enantioselective Decarboxylation of 2-Methyl-2-aminomalonate Catalyzed by (S)-2-Hydroxy-2'-(3-phenyluryl-benzyl)-1,1'-binaphthyl-3-carboxaldehyde

Abstract

Figure 1. (a): The H NMR spectrum of DMSO-d6 solution of 1 only. (b)-(d): The H NMR spectra of DMSO-d6 solution of 1 + [Me4N] [MAM-H] in 10 min, 1.5 h and 10 h. All the peak assignments in (d) are for the imines of 1-D-Ala and 1-L-Ala, and the peak assignment in (b) and (c) is for free [Me4N][MAM-H]. Aminomalonic acid (AM-H2) is a biological intermediate appearing in the conversion course of serine to glycine. Aminomalonic decarboxylases, enzymes that catalyze decarboxylation of aminomalonic acid, have been found in many living systems. Serine hydroxymethyltransferase stereospecifically decarboxylates 2-amino-2-methyl-malonic acid (MAM-H2) to produce D-alanine. Although stereoselective decarboxylation is a century old theme, the interest on it is growing recently owing to the development of chiral technology. Chemical approaches using metal complexes and cinchonine derivatives have been developed for stereospecific decarboxylation of MAM. Rate constant for the spontaneous decarboxylation of aminomalonate at pH 2-3 and 25 C was reported to be 1.1 × 10‒6 s‒1, which corresponds to half-life (t1/2) of 175 h. In the presence of 1.0 M acetone, the rate is enhanced to ~100-fold. Moreover, Thanassi reported a rate constant of ~4 × 10‒3 s‒1 for the 5-deoxypyridoxal catalyzed decarboxylation of MAM at pH 5. The rate enhancement in both cases are due to the imine formation. These studies encouraged us to employ (S)-2-hydroxy-2'-(3phenyluryl-benzyl)-1,1'-binaphthyl-3-carboxaldehyde (1) as a stereoselective chemical decarboxylase. Compound 1 was initially designed for stereoselective recognition of amino acids and amino alcohols by imine formation. We report here the decarboxylation of MAM catalyzed by 1.