76410-58-7

white to off-white powder

4-Borono-L-phenylalanine is an unnatural derivative of L-Phenylalanine (P319415). a nonpolar, essential amino acid that naturally occurs in the human body and is also used to treat patients with depression. 4-Borono-L-phenylalanine is also being used as a mediator in sequential boron neutron capture therapy, a new method of treating oral cancer.

The general procedure for the synthesis of (S)-2-amino-3-(4-boronic acid phenyl)propionic acid from (S)-3-(4-boronic acid phenyl)-2-((tert-butoxycarbonyl)amino)propionic acid was as follows: (S)-N-Boc-4-borophenylalanine (5.63 g, 98.5% purity, 17.9 mmol) was suspended in a solvent mixture of acetone (34 mL) and water (3.8 mL). Concentrated hydrochloric acid (37%, 3.8 mL) was added slowly under stirring to form an acidic reaction system. The reaction system was stirred at 55 °C for 1.5 h. HPLC showed that the reaction was complete. The reaction system was cooled to room temperature and the pH was adjusted to 1.5 with aqueous sodium hydroxide solution and stirred for 30 min, during which (S)-2-amino-3-(4-boronic acid phenyl)propionic acid started to precipitate. Subsequently, the pH of the reaction system was re-adjusted to 6.2 with aqueous sodium hydroxide and stirring was continued overnight at room temperature. Upon completion of the reaction, the solid product was collected by filtration to afford (S)-2-amino-3-(4-boronic acid phenyl)propionic acid.

[1] Patent: EP2865682, 2015, A1. Location in patent: Paragraph 0077; 0078
[2] Patent: US2018/155368, 2018, A1. Location in patent: Paragraph 0123-0128
[3] Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 1, p. 231 - 235