Access to β,γ-diamino acids. Application to the synthesis of 3-deoxyaminostatine

Abstract

The synthesis of orthogonally protected diastereo- and enantiopure β,γ-diamino acids starting from natural α-amino acids is described, as well as its application to the synthesis of fully protected 3-deoxyaminostatine.

Constrained Cyclic β,γ‐Diamino Acids from Glutamic Acid: Synthesis of Both Diastereomers and Unexpected Kinetic Resolution

“…For example, the natural α-amino acid L-proline is known to form polyproline helices, [1] or to generate turns when associated with glycine. [20][21][22][23][24][25] This pattern is present in some biologically active compounds such as pseudotheonamide A 1 , [26] aminocarnitine, [27] and deoxyaminostatine, [28] but the main interest in this motif lies in its use as either a -amino acid or a γ-amino acid building block for foldamers. [2][3][4][5][6][7][8][9] A large variety of helices, [10][11][12][13][14] turns, [15] sheets, [16] and ribbons [17,18] have been observed in this way, even in the less explored area of γ-peptides.…”

“…[19] In our group, we have been interested for a few years in the synthesis and use of ,γ-diamino acids. [20][21][22][23][24][25] This pattern is present in some biologically active compounds such as pseudotheonamide A 1 , [26] aminocarnitine, [27] and deoxyaminostatine, [28] but the main interest in this motif lies in its use as either a -amino acid or a γ-amino acid building block for foldamers. The presence of the second nitrogen could either allow further function-an interesting kinetic resolution during the synthesis that allowed easier separation of diastereomers.…”

Frozen Chirality of Tertiary Aromatic Amides: Access to Enantioenriched Tertiary α‐Amino Acid or Amino Alcohol without Chiral Reagent

“…Our research group has, over a few years, developed several asymmetric syntheses of nonproteinogenic amino acids starting from natural α‐amino acids, by using the initial chirality of the reacting α‐amino acid as the unique source of chirality. We have thus synthesized enantiopure β,γ‐diamino acids through a classical diastereoselective synthesis and quaternary α‐amino acids relying on the Memory of Chirality (MOC) principle . The next step was an extension of this latter methodology to the great challenge of absolute asymmetric synthesis of tertiary α‐amino acids; that is, to get rid of the initial chirality and to start from the simplest achiral α‐amino acid, glycine.…”