102608-37-7

Upstream product

• 60656-87-3 benzyloxyacetoaldehyde 
• 56-40-6 glycine 
• 65564-05-8 3-[(benzyloxycarbonyl)amino]propanal 
• 102608-36-6 (2S),(3R)-3-benzyloxyoxiranecarboxylic acid 

Downstream Products

• 102608-38-8 (4S,5S)-5-Benzyloxymethyl-2-oxo-oxazolidine-4-carboxylic acid 

Relevant academic research and scientific papers

Serine hydroxymethyl transferase from Streptococcus thermophilus and L-threonine aldolase from Escherichia coli as stereocomplementary biocatalysts for the synthesis of β-hydroxy-α,ω-diamino acid derivatives

A novel serine hydroxymethyl 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 = benzyloxycarbonyl). 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 L-threo 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°C SHMT has high synthetic activity but negligible retroaldol 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-γ-amino-β-hydroxy-αamino acid derivatives with potassium hydroxide (1M) resulted in the spontaneous formation of 2-oxazolidinone derivatives of the β-hydroxyl and γ-amino groups in quantitative yield. This reaction might be useful for further chemical manipulations of the products.

Enzymatic synthesis of ω-carboxy-β-hydroxy-(l)-α-amino acids

Commercially available ω-carboxy-aldehydes and glycine have been subjected to the catalytic action of an l-threonine aldolase from Escherichia coli to give the corresponding β-hydroxy-α-(l)-amino acids as a mixture of erythro/threo epimers. Specifically, the reaction with glyoxylic acid (2) gave the epimeric β-hydroxy-(l)-aspartates (t,e)-9 that could be isolated by ion-exchange chromatography in 67% yield. Following esterification and N-Boc protection, the two epimers could be isolated as pure compounds. Similarly, the aldolase-catalyzed addition of glycine to succinic semialdehyde (4) gave the expected mixture of β-hydroxy-l-α-aminoadipic acids (t)-12 and (e)-12 in 34% yield.

Enzymatic synthesis of β-hydroxy-α-amino acids based on recombinant D- and L-threonine aldolases

To exploit the enzymatic method for the synthesis of β-hydroxy-α-amino acids, the genes coding for the Escherichia coli L-threonine aldolase (LTA; EC 2.1.2.1) and Xanthomonus oryzae D-threonine aldolase (DTA) were cloned and overexpressed in E. coli through primer-directed polymerase chain reactions. The purified recombinant enzymes were studied with respect to kinetics, specificity, stability, additive requirement, temperature profile, and pH dependency. DTA requires magnesium ion as a cofactor, while LTA needs no metal ions. These enzymes work well in the presence of DMSO with concentration up to 40%, and DMSO-induced rate acceleration of LTA-catalyzed reaction was observed. Both enzymes use pyridoxal phosphate coenzyme to activate glycine to react with a wide range of aldehydes. LTA gave erythro-β-hydroxy-α-L-amino acids with aliphatic aldehydes and the threo isomer with aromatic aldehydes as kinetically controlled products. On the other hand, DTA formed threo-β-hydroxy-α-D-amino acids as kinetically controlled products with aliphatic and aromatic aldehydes but the diastereoselectivity was lower than that of LTA. Under optimal conditions, several β-hydroxy-α-amino acid derivatives (3-hydroxyleucines, γ-benzyloxythreonines, γ-benzyloxymethylthreonines, and poplyoxamic acids) have been stereoselectively synthesized on preparative scales using these enzymes. Also, the tandem use of DTA and phosphatases has made possible the synthesis and separation of D-allo-threonine phosphate and D-threonine.

Kinetic and thermodynamic control of L-threonine aldolase catalyzed reaction and its application to the synthesis of mycestericin D

L-Threonine aldolase catalyzes the aldol condensation of γ-benzyloxybutanal and glycine with high erythro/threo selectivity under a kinetically controlled condition. The erythro product was used in the synthesis of mycestericin D, a potent immunosuppressant.