β‐Amino‐γ,γ‐difluoro‐ω‐phosphonoglutamic Acid Derivatives: An Unexplored, Multifaceted Structural Type of Tailor‐Made α‐Amino Acids

• Published in: European journal of organic chemistry 2017-06, Vol.2017 (24), p.3451-3456
• Main Authors: Zhang, Wenzhong, Sha, Wanxing, Pajkert, Romana, Mei, Haibo, Pan, Yi, Han, Jianlin, Röschenthaler, Gerd‐Volker, Soloshonok, Vadim A.
• Format: Article
• Language: English
• Subjects: Amino acids; Asymmetric synthesis; Fluorinated compounds; Mannich reaction; Peptides
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201700570

Properly protected glycinates (Schiff base, alkyl/aryl ester) cleanly reacted with chiral sulfinyl‐derived difluoro(phosphoryl)aldimines under ambient conditions in THF in the presence of a catalytic amount of Cs2CO3. The procedure was operationally simple and provided the target addition products in good (60–80 %) yields with excellent (99:1) diastereoselectivity. This approach allowed the preparation of a structural type of biologically interesting molecules comprising α,β‐diamino acid, carboxylic acid, and phosphonic acid structural features. Chemoselective operation of the α‐ and β‐amino functional groups was demonstrated by the preparation of all‐α‐ and mixed‐α,β‐amino acid derived dipeptides. A structural type of biologically important compounds featuring fluoro, α‐ and β‐amino acid, α,β‐diamino acid, carboxylic acid, and phosphonic acid functional characteristics all in one molecule is designed, synthesized, and successfully used for the preparation of all‐α‐ and mixed‐α,β‐dipeptides.