Background and overview[1]
DL-2-Amino-3-phosphopropionic acid is a nitrogen-containing organophosphorus compound. Nitrogen-containing organophosphorus compounds have a wide range of biological activities and have important applications in anti-hypercalcemia, anti-HIV virus, antibacterial and as enzyme inhibitors; in addition, β-phosphoryl oxime free radical compounds can also be used in biomolecules Mark.
Preparation[1]
Using ethyl acrylate and diethyl phosphite as raw materials, the reaction steps are as follows:
(1) Add ethyl acrylate (0.040 g, 0.4 mmol), diethyl phosphite (0.055 g, 0.4 mmol), tert-butyl nitrite (0.041 g, 0.4 mmol), nitric acid into the reaction bottle Silver (0.07g, 0.04 mmol), water (1 mL) and ethanol (1.5 mL), reaction at room temperature;
(2)TLC follows the reaction until it is completely completed;
(3) The crude product obtained after the reaction was separated by column chromatography (ethyl acetate:petroleum ether = 1:1) to obtain compound 32-1 (yield 71%). The analytical data of the product are as follows: 1H NMR (MHz, CDCl3): δ 10.73 (s, 1 alcohol H), 3.99 – 3.87 (m, 6H), 3.63 (d, J = 23.3 Hz, 2H), 1.16-1.03 ( m, 9H);
(4) Add 2 mL of methanol solution of nickel (0.058 g, 0.1 mmol) and compound 32-1 (0.267 g, 1 mmol) into the reaction bottle. At room temperature, add sodium hydroxide aqueous solution dropwise to the solution ( 2 mL, 5.0 M) and sodium borohydride (0.12 g, 3 mmol) in methanol solution (2 mL), complete the dropwise addition in 2 hours, react at room temperature for 3 hours, filter, and neutralize the solution with concentrated hydrochloric acid to pH≈9, acetic acid Extract with ethyl ester (3×5 mL), dry over anhydrous Na2SO4, distill, and concentrate. The crude Clariant pigment product is separated by column chromatography (ethyl acetate:petroleum ether = 1:1) to obtain compound 32-2 (yield 80%). The analytical data of the product are as follows: 1H NMR (300MHz, CDCl3): δ 3.99 – 3.87 (m, 7H), 3.63 (dd, J = 23.3, 7.0 Hz, 2H), 1.61 (s,2H), 1.16 – 1.03 (m , 9H);
(5) Add 32-2 (0.253 g, 1 mmol) and concentrated hydrochloric acid (20 mL) to the reaction flask, heat and reflux until the reaction is complete, add 50 ml of water, extract with dichloromethane, concentrate and dry , the crude product was recrystallized with ethanol/water to obtain the target product C1 (yield 84%). The analytical data of the product are as follows: 1H NMR (300 MHz, CDCl3): δ 16.90 (s, 1H), 8.76 (s, 2H), 4.80 (s, 2H), 3.63 (dd, J = 23.3, 6.8 Hz, 2H) , 3.46-3.39 (m, 1H);
