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

Abstract 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− 13 C]Serine is cyclized to its β‐lactone which was treated with potassium [ 13 C]cyanide to yield L‐β‐[3,4− 13 C 2 ]cyanoalanine. Hydrolysis of the cyanoalanine yielded L‐[3,4− 13 C 2 ]aspartic acid. Similarly, L‐[4− 13 C]aspartate was produced from L‐serine and K 13 CN. Using this route, the L‐enantiomer was produced in 96% excess.