Uses
Boc-D-4,4'-biphenylalanine is used as a reagent in the synthesis of pyrrolopyrimidine inhibitors of Akt as antitumor agents. Boc-D-4,4'-biphenylalanine is also used in the preparation of (-)-Bestatin-based inhibitors.
Synthesis
To a mixed solution of tetrahydrofuran (THF) (80 mL) and water (80 mL) of (S)-3-([1,1'-biphenyl]-4-yl)-2-aminopropanoic acid (25) (5 g, 20.72 mmol) was added di-tert-butyl dicarbonate (BOC2O) (5.77 mL, 24.87 mmol) and sodium hydroxide (NaOH) (1.077 g. 26.9 mmol). The reaction mixture was stirred at room temperature for 6 hours before being cooled to 0 °C and the pH was adjusted to about 6-7 by slowly adding 1.5 N aqueous hydrochloric acid (HCl) to quench the reaction. Subsequently, the reaction mixture was extracted with ethyl acetate (EtOAc) (3 x 50 mL). The combined organic layers were washed sequentially with brine (50 mL) and water (50 mL), dried over anhydrous sodium sulfate and concentrated to give the crude product as a colloidal off-white solid. The crude product was purified by washing with petroleum ether (PE) with 10% ethyl acetate (4 x 20 mL). The resulting white solid was filtered and dried under vacuum to afford (S)-3-([1,1'-biphenyl]-4-yl)-2-((tert-butoxycarbonyl)amino)propionic acid (26) (6.5 g, 19.04 mmol, 92% yield). The product was analyzed by 1H NMR (400 MHz, DMSO-d6) and mass spectrometry (ESI) to confirm the structure.1H NMR data: δ 7.67-7.62 (m, 2H), 7.58 (d, J=8.5 Hz, 2H), 7.50-7.43 (m, 2H), 7.39-7.31 (m, 3H), 7.10 (d, J=8.0 Hz. 1H), 4.17-4.07 (m, 1H), 3.07 (dd, J=13.6,4.5Hz, 1H), 2.88 (dd, J=13.6,10.0Hz, 1H), 1.37-1.23 (m, 9H). Mass spectral data: 340.2 ([M-1]-).
