Expeditious Synthesis of Enantiopure, Orthogonally Protected Bis-α-Amino Acids (OPBAAs) and their Use in a Study of Nod1 Stimulation

A convenient approach towards the synthesis of orthogonally protected chiral bis-alpha-amino acids (OPBAAs) is described. The key transformations include: (1) a highly stereoselective conjugation (alkylation) of the Schollkopf bislactim ethers and oxazolidinyl alkyl halides to build a backbone skeleton; and (2) our orthogonal protection strategy. A series of enantiopure OPBAAs bearing a variety of alkyl chain as a spacer; two stereogenic centers; and three protecting groups were prepared as examples. These versatile molecules were applied to the synthesis of biologically interesting di-or tri-peptide analogues, including chiral iE-meso-DAP and A-iE-meso-DAP, for the study of Nod1 activation in the innate immune response.