Divergent synthesis of biologically active l-threo-β-hydroxyaspartates from common trans-oxazolidine dicarboxylate

• Published in: Amino acids Vol. 54; no. 12; pp. 1601 - 1610
• Main Authors: Lee, Yoonjae, Seo, Youngran, Lee, Boram, Kwon, Hyuenyoung, Chung, Kyungsu, Kim, Young Gyu
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.12.2022; Springer Nature B.V
• Subjects: Amino acids; Analytical Chemistry; Antibiotics; Aqueous solutions; Biochemical Engineering; Biochemistry; Biological activity; Biomedical and Life Sciences; Carboxylic acids; Chromatography; Divergence; Hydroxy acids; Life Sciences; Neurobiology; Oxazolidine; Proteomics; Short Communication; Stereoselectivity; β-hydroxyaspartate; Depsipeptide; -; oxazolidine dicarboxylate; Building block; α-Amino-β-hydroxy acids
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-022-03196-8

A divergent synthetic strategy starting from a common trans -oxazolidine dicarboxylate intermediate has been successful to produce several non-proteinogenic l - threo -β-hydroxyaspartate derivatives efficiently with high stereoselectivity. Three bioactive α-amino-β-hydroxy acids, l - threo -β-hydroxyaspartic acid, l - threo -β-hydroxyasparagine, and l - threo -β-benzyloxyaspartic acid, were synthesized in good yields (58–83%) from the common chiral intermediate, and the chemoselective peptide bond formation at the α-amino group, β-hydroxy group, or α-carboxylic acid of the common intermediate was possible to afford the corresponding dipeptide, tripeptide, or didepsipeptide intermediate in 46~77% yields (in three-to-four steps) due to the orthogonal protective groups on the chiral intermediate.