Hydroxymethyl Transferase from Streptococcus thermophilus and L-Threonine Aldolase from Escherichia coli as Stereocomplementary Biocatalysts for the Synthesis of beta-Hydroxy beta-omega-diamino Acid Derivatives

A novel serine hydroxy-methyl transferase from Streptococcus thermophilus (SHMT) and a l-threonine aldolase from Escherichia coli (lTA) were used as stereocomplementary biocatalysts for the aldol addition of glycine to N-Cbz amino aldehydes and benzyloxyacetaldehyde (Cbz=benzyloxyarbonyl). Both threonine aldolases were classified as low-specific l-allo-threonine aldolases, and by manipulating reaction parameters, such as temperature, glycine concentration, and reaction media, SHMT yielded exclusively l-erythro diastereomers in 34– 60% conversion, whereas lTA gave lthreo diastereomers in 30:70 to 16:84 diastereomeric ratios and with 40–68% conversion to product. SHMT is among the most stereoselective l-threonine aldolases described. This is due, among other things, to its activity–temperature dependence: at 4 8C SHMT has high synthetic activity but negligible retro- ACHTUNGTRENUNGaldol activity on l-threonine. Thus, the kinetic l-erythro isomer was largely favored and the reactions were virtually irreversible, highly stereoselective, and in turn, gave excellent conversion. It was also found that treatment of the prepared N-Cbz-gamma-amino-beta-hydroxy-alfa-amino acid derivatives with potassium hydroxide (1m) resulted in the spontaneous formation of 2-oxazolidinone derivatives of the beta-hydroxyl and gamma-amino groups in quantitative yield. This reaction might be useful for further chemical manipulations of the products.