Chiral Amplification of Phosphoramidates of Amines and Amino Acids in Water

Abstract

The origin of biomolecular homochirality continues to be one of the most fascinating aspects of prebiotic chemistry. Various amplification strategies for chiral compounds to enhance a small chiral preference have been reported, but none of these involves phosphorylation, one of nature's essential chemical reactions. Here we present a simple and robust concept of phosphorylation-based chiral amplification of amines and amino acids in water. By exploiting the difference in solubility of a racemic phosphoramidate and its enantiopure form, we achieved enantioenrichment in solution. Starting with near racemic, phenylethylamine-based phosphoramidates, ee's of up to 95 % are reached in a single amplification step. Particularly noteworthy is the enantioenrichment of phosphorylated amino acids and their derivatives, which might point to a potential role of phosphorus en-route to prebiotic homochirality.

Keywords: amino acid; chiral amplification; origin of life; phosphoramidate; phosphorylation.

Scheme 1

Synthesis of phosphoramidate 1 via Atherton–Todd reaction.

Figure 1

Zoom in of the ternary phase diagram of (S)‐1, (R)‐1 and water at 26 °C.

Figure 2

Structure of racemic dimer phosphoramidate rac‐1 in the crystal. C−H hydrogen atoms are omitted for clarity. ^[29]

Figure 3

Chiral amplification of (S)‐/(R)‐/rac‐diisopropyl (1‐ phenylethyl)phosphoramidate 1 in water at 26 °C. [a] Determined by chiral HPLC analysis.

Figure 4

Phosphoramidates.

Figure 5

Chiral amplification results of phosphoramidate 1, 4 and 5 in water at 26 °C [a] Determined by chiral HPLC analysis.

Figure 6

Chiral amplification results of phosphoramidate 7, 8, 9 and 10 in water at 26 °C. [a] Determined by chiral HPLC analysis.

Scheme 2

Synthesis and structures of phosphorylated amino acids and their methyl ester derivatives 14–21 (Dipp=diisopropyloxyphosphoryl).

Figure 7

Amplification of phosphorylated amino acids and methyl ester derivatives 14, 16, 17, 19 and 20 in water at 26 °C. [a] Determined by chiral HPLC analysis.