535967-29-4

Upstream product

• 392-12-1 Indole-3-pyruvic acid 
• 87438-91-3 ethyl 2-((1H-indol-3-yl)methyl)acrylate 

Downstream Products

• 146142-94-1 (2S,4S)-2-((1H-indol-3-yl)methyl)-4-amino-2-hydroxypentane-1,5-dioic acid 

Relevant academic research and scientific papers

Preparation and characterization of four stereoisomers of monatin

Monatin is a naturally occurring, sweet amino acid comprising four stereoisomers due to its two asymmetric centers at C2 and C4. However, the characteristics of each stereoisomer have not yet been fully investigated. To obtain a sufficient amount of racemic monatin for optical resolution, a synthetic method was developed by modifying a possible biosynthetic pathway, i.e., a cross-aldol reaction and subsequent transamination. The key intermediate, 4-hydroxy-4-(3-indolylmethyl)-2-ketoglutaric acid, was obtained via the cross-aldol reaction of pyruvic acid and indole-3-pyruvic acid. Subsequently, the carbonyl group was converted to a hydroxyimino group through reaction with hydroxylamine and then to an amino group via hydrogenation to produce monatin. Next, the racemic monatin was divided into mixtures of two pairs of enantiomers through recrystallization. Finally, both enantiomers of the N-carbobenzoxy-γ-lactone derivatives of monatin were separated by preparative HPLC and deprotected. It was found that all optically pure stereoisomers exhibited a sweet taste. The isomer that displayed the most intense sweetness was the (2R,4R)-isomer, as determined by single crystal X-ray structure analysis of the monatin potassium salt, whereas the least sweet isomer was the (2S,4S)-isomer, which demonstrated a far lower sweetness than was previously reported.

Scale-up of a chemo-biocatalytic route to (2 R,4 R)- and (2 S,4 S)-monatin

Monatin, a natural sweetener, refers to a collection of four isomers of 2-((1H-indol-3-yl)methyl)-4-amino-2-hydroxypentanedioic acid. A chemo-biocatalytic approach to kilogram quantities of enantiopure 2S,4S-monatin and 2R,4R-monatin from indole is described. Key steps in the process include a (2 + 3) cycloaddition reaction followed by nickel-catalysed reduction to construct the monatin backbone, and a highly selective enzyme resolution of the 2S,4S- and 2R,4R-monatin diastereomeric pair to afford each enantiomer in 99% ee.

PRODUCTION OF MONATIN STEREOISOMERS

Methods and materials for the production of the high intensity sweetener, monatin, in stereoisomerically-pure or stereoisomerically-enriched form are disclosed. For example, methods using stereoisoselective hydrolysis and separation of a monatin-derived lactone ester are disclosed.