Preparation of adenine phosphate_industrial additives

Background and overview^[1][2]

Adenine phosphate drugs are a new class of drugs developed in the past 20 years for anti-metabolic bone diseases. They are a pyrophosphate analogue that replaces the P-O-P bond in the latter with a P-C-P bond and is used to treat Osteoporosis, osteitis deformans, multiple myeloma (MM), hypercalcemia and bone pain caused by malignant tumor bone metastasis and other bone metabolic diseases. Adenine phosphate is particularly suitable for the treatment of osteoporosis, which is “characterized by a decrease in bone mass and destruction of bone structure, leading to increased bone fragility and fracture rates.” The latest research shows that adenine phosphate drugs can also play an anti-tumor role by promoting tumor cell apoptosis, inhibiting the release of tumor growth factors, and affecting tumor cell adhesion, invasion, and vitality.

Adenine phosphate

Apply^[3]

At present, the medical community generally believes that the fundamental reason why most anti-cancer drugs, such as topoisomerase inhibitors, alkylating agents, anti-metabolite drugs and hormone antagonists, can kill cancer cells is that these drugs can Induces apoptosis in different types of cancer cells. Experiments by many researchers have also confirmed that adenine phosphate is used for leukopenia caused by various reasons, especially leukopenia caused by tumor chemotherapy, radiotherapy, and poisoning by benzene and other drugs. Adenine phosphate is often used together with hormones or other vitamins and other drugs and blood transfusions.

Preparation^[2]

Synthesis of crude adenine phosphate:

Place adenine (10.8g, 0.08mol) in a four-neck bottle, add 100ml of DMF, and heat to 100°C. Adenine is insoluble. After cooling to room temperature, add anhydrous Na2CO3 (8.2g, 0.08 mol), reacted at 100°C for 30 minutes, then lowered to 80°C, and slowly added ethyl monochloroacetate (17ml, 0.16mol) dropwise. After the dripping was completed, the temperature was kept at 80°C and the reaction was stirred. The reaction process was monitored by TLC. After 8 hours, the mixture was cooled and filtered with suction to obtain a dark yellow solid. After drying under an infrared lamp, the total solid amount was 19 g.

Refining of adenine phosphate

Take 8g of crude adenine phosphate, add 200ml of Kao antistatic agent ethanol, heat to boiling, and filter while hot to remove alcohol-insoluble matter. Add an appropriate amount of activated carbon to the filtrate, heat and reflux for about 15 minutes, then filter while hot. The filtrate is cooled to room temperature, and white flaky crystals precipitate. The adenine phosphate yield is 73.7%.