ИСТИНА

Chiral unnatural amino acids (AAs) are important intermediates in pharmaceutical industry and biochemistry. Among them, AAs featuring heterocyclic cores have a considerable interest, in particular, a 3-spiropyrrolidine oxindole skeletal is presented in various biologically active compounds with pronounced therapeutic properties. We recently developed a useful protocol for the asymmetric synthesis of artificial AAs comprising a 3-spiropyrrolidine oxindole skeletal with continuous tetrasubstituted carbon stereocenters by a 1,3-dipolar cycloaddition reaction of in situ generated azomethine ylides with a chiral dehydroalanine Ni(II) complex 1. A three-component reaction of the Ni(II) complex with various isatins 2 and AAs 3 in ethanol provided a series of diastereomeric complexes 4 with high dr (>20:1) in 40–86% yields. The acidic decomposition of the obtained Ni(II) complexes led to the target unnatural AAs with a 3-spiropyrrolidine oxindole core 5.