Synthesis of derivatives of ω-isocyanato-α-methylamino, ω-ureido-α-methylamino, and N^α-methyl-α,ω-diamino acids

Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b - the key intermediates of the synthesis - are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N^ω-urethane protected ω-amino-α-methylamino acid derivatives 5-7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10-12 and 3-methylamino-pyrrolidin-2-ones 13 are available.