Z-Phe-Ala-OH

Chemical Properties

White to off-white powder

Uses

Sensitive substrate for cathepsin A.

Synthesis

The general procedure for the synthesis of the compound (CAS:3338-39-4) from (S)-2,5-dioxopyrrolidin-1-yl 2-(((benzyloxy)carbonyl)amino)-3-phenylpropanoate and L-alanine was as follows: with reference to the method of Itoh [M. Itoh, Chem. Pharm. Bull., 20, 664 (1972)], to L- alanine (18 mmol, 1.60 g) dissolved in 200 mL of a 1:1 dioxane-water mixture to triethylamine (36 mmol, 5.0 mL). Solid carbon dioxide tablets were added under stirring conditions until the solution pH reached 8. Subsequently, N-Benzyloxycarbonyl-L-phenylalanine N-hydroxysuccinimide ester (18 mmol, 7.13 g) was added under stirring at room temperature. After 16-20 hours of reaction, the reaction mixture was acidified by slow addition of 1N HCl followed by extraction with ethyl acetate. The organic phase was separated, washed sequentially with water (twice) and brine, dried over MgSO4, concentrated by rotary evaporation and dried under high vacuum to give 6.19 g (93% yield) of N-Benzyloxycarbonyl-L-phenylalanyl-L-alanine as a white solid with a melting point of 160-164 °C (literature value: 165 °C; G.R. Pettit, 'Synthetic Peptides', Vol. 1, p. 141 (1970)). Using similar methods, the following compounds of formula (2) can be prepared according to the procedure described in Preparation 1.

References

[1] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6230 - 6237
[2] Patent: US5055451, 1991, A
[3] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 3, p. 1071 - 1078