Z-ALA-PRO-PNA synthesis

Yield:-

Reaction Conditions:

with N-ethylmorpholine in tetrahydrofuran;ethyl acetate;

Steps:

5.i (i)

(i) N-Benzyloxycarbonyl-L-alanyl-L-proline 4-nitroanilide 3.2 g (0.01 mole) of N-benzyloxycarbonyl-L-alanyl-L-proline were dissolved in 50 ml of dry tetrahydrofuran and the solution was cooled to -10° C. 1.27 ml (0.01 mol) of N-ethylmorpholine were added followed by 1.31 ml (0.1 mol) of isobutyl chloroformate and the mixture was stirred at -10° C. for 20 minutes. 1.38 g (0.01 mol) of 4-nitroaniline were then added, the mixture was stirred at 0° C. for 1 hour and then left to stand at room temperature for 72 hours. The mixture was then evaporated and the residue dissolved in 100 ml of ethyl acetate. The solution was washed with 80 ml of 1-N hydrochloric acid, 80 ml of water and 80 ml of 5% sodium bicarbonate solution, dried over magnesium sulphate and evaporated. The resulting oil was chromatographed on 100 g of silica gel using chloroform for the elution. The residue obtained after evaporating the chloroform elude was taken up in ether and left to stand for 16 hours, the pure crystalline N-benzyloxycarbonyl-L-alanyl-L-proline 4-nitroanilide separating out. The yield was 1.5 g (34%) and the melting point 160°-163° C.; [α]_D²⁰ =-178.1° (c=0.975% in methanol). Analysis for C₂₂ H₂₄ O₆ N₄ (440.46): Calculated: C: 59.99; H: 5.49; N: 12.72. Found: C: 59.74; H: 5.67; N: 12.51.

References:

US4187216,1980,A