Aldol condensations amino acid metal complexes

Watanabe, K.-L Yamada, Y. Goto, K. (1985) New type aldol condensations catalyzed by metal(ll) complexes of a-amino acid esters and that with cyclodextrin systems. Bull. Chem. Soc. Jpn, 58,1401-6. 

Proline is a stable, nontoxic, cyclic, secondary pyrrolidine-based amino acid with an increased pK value. Thus, proline is a chiral bidentate compound that can form catalytically active metal complexes (Melchiorre et al. 2008). Bidentate means that proline has not only one tooth but also a second one to bite and react. The greatest difference to other amino acids is a Lewis-base type catalysis that facilitates iminium and enamine-based reactions. It is especially noteworthy that cross-aldol condensations of unprotected glycoladehyde and racemic glyceralde-hyde in the presence of catalytic amounts of the Zn-(proline)2 gave a mixture of pentoses and hexoses (Kofoed et al. 2004). Again, proline seems to play the decisive role. The conditions are prebiotic the reaction proceeded in water for seven days at room temperature. It is remarkable that the pentose products contained ribose (34%), lyxose (32%), arabinose (21%), and xylose (12%) and that all are stable under the conditions. Thus, the diastereomeric and enantiomeric selection observed support the idea that amino acids have been the source of chirality for prebiotic sugar synthesis. 

A substantial enhancement of the condensation rate of these substances is observed by using hydrotropes such as sodium butylmonoglycosulfate (NaBMGS) and the sodium salts of aromatic sulfonic acids in alkaline media [8]. In the absence of NaOH, the reaction does not proceed, which indicates that the hydrotropes do not catalyze the reaction and that the effect is simply that of the solubilization of the reactants at higher concentrations. The selectivity of the reaction of p-nitrobenzaldehyde with acetone can be controlled in aqueous media by working in the presence of zinc nitrate hexahydrate and A,A-dimethylaminoethanol [9]. The amino alcohol-zinc combination favors aldol addition at pH 9.1-9.5 and aldol condensation at pH 11.4. The same reaction catalyzed by metal complexes bearing ligands of the a-amino acids... 

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