Stereoselective Synthesis of Stable Isotope Labeled L-α-Amino Acids: Synthesis of L−[4−13C] and L−[3,4−13C2]Aspartic Acid

We have developed a stereoselective route to isotopically labeled L‐aspartic acid using L‐serine as a chiral precursor. Labeled serine, prepared biosynthetically was N‐protected by conversion to the N‐t‐Boc derivative. (N‐t‐Boc)‐[3−13C]Serine is cyclized to its β‐lactone which was treated with potassium [13C]cyanide to yield L‐β‐[3,4−13C2]cyanoalanine. Hydrolysis of the cyanoalanine yielded L‐[3,4−13C2]aspartic acid. Similarly, L‐[4−13C]aspartate was produced from L‐serine and K13CN. Using this route, the L‐enantiomer was produced in 96% excess.