Syntheses of (2S,3R)- and (2S,3R)2H>- 3-Methylaspartic acid: Slow Substrates for a syn-Elimination Reaction catalysed by Methylaspartase.

Article abstract of DOI:10.1016/S0957-4166(00)80221-9

Methylaspartase catalyses the slow syn-elimination of ammonia from the (2S,3R)--diastereomer of the natural substrate, (2S,3S)-3-methylaspartic acid, to give mesaconic acid.To provide material of sufficient stereochemical purity to probe the mechanism of the reaction, two synthetic routes to (2S,3R)- and (2S,3R)<3-²H>- 3-methylaspartic acid were devised.The use of these (2S,3R)-3-methylaspartic acids revealed that the enzymic reaction does not involve C-3 epimerisation followed by normal anti-elimination, ruling-out the possibility of a carbanion intermediate.Conversely, the substrate displayed very large primary deuterium isotope effects indicating rate-limiting C-H bond cleavage.