GAMMA AMINO ACID BUILDING BLOCKS

摘要

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a pro line derivative to provide cyclically constrained a-substituted-?-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected ?- amino acid residues, which are essential for systematic conformational studies of ?-peptide foldamers. New methods are also provided to prepare other ?-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as a/?-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.