EXTENDED ACCESS TO CHIRAL α,α-DISUBSTITUTED α-AMINO ACIDS VIA TRANSFORMATION OF α-ALKYLSERINE TO β-LACTONES

摘要

N-Protected β-lactones of serine, threonine and cysteine are useful and versatile intermediates in the enantioselective synthesis of β-substituted-α-amino acid via ring opening by various nucleophiles. A large variety of carbon, nitrogen, oxygen, sulfur, and halogen nucleophiles were used to attack chiral N-protected serine β-lactones at the β-carbon yielding optically pure N-protected β-substituted alanines . On the other hand, building blocks such as α,α-disubstituted amino acids have become important in medicinal chemistry and biochemistry. Incorporation of these units into peptides results in conformational restrictions and increased constraints of the peptidomimetic structures. α,α-Disubstituted amino acids have been successfully used to force peptides into their biologically active conformations, often resulting in nentidomimetics with remarkable resistance to enzvmatic degradation.