Synthesis of L-valine NCA (Val NCA)

_L-valine NCA was synthesised using a modified procedure from previously reported literature⁴⁴. Briefly, _L-valine (43 mmol, 5 g) was suspended within 80 mL of anhydrous THF in a two-necked round bottom flask under argon. Triphosgene (1.2× excess: 17 mmol, 5.1 g) was added and the mixture was continuously stirred 60 °C for 2 h or until all valine had dissolved. The reaction mixture was sparged with argon into a saturated NaOH solution for 1 h after which solvent was removed in vacuo (20 mbar, 40 °C) until equilibrium. The reduced mixture was redissolved in anhydrous 50 mL ethyl acetate which was chilled in 5 °C and then washed with saturated brine at 5 °C and 0.5 w/v % sodium bicarbonate aqueous solution at 5 °C with the organic phase being washed after separation each time. The resulting organic phase was dried using magnesium sulphate with the filtrate being reduced in vacuo (20 mbar, 50 °C) until equilibrium. The residue was recrystallised using n-pentane overnight. The resulting crystals were filtered and reprecipitated to afford a white powder (~60% Yield). ¹H NMR (400 MHz, CDCl₃): δ_H 0.92 (dd, 6 H, CH₃), 2.00–2.18 (m, 1 H, CH), 4.08 (dd, 1 H, cyclic CH), 8.84 (s, 1 H, cyclic NH).