Background and overview[1-2]
Cyclic adenosine 3′, 5′-cyclic monophosphate (cAMP industrial additive) is the second messenger of growth hormone, epinephrine and other hormones, and is an important regulator of animal body metabolism. Some data show that it has special effects on angina pectoris, acute myocardial infarction, and psoriasis. Bucladesinesodium is a derivative of cyclic adenosine monophosphate, which is used to treat cardiogenic shock and heart failure. In 1999, Bucladesinesodium ointment was developed for the treatment of skin infections, Skin ulcers.
Preparation[1-2]
Method 1: Preparation of sodium dibutyryl cyclic adenosine monophosphate: Slowly add sodium hydroxide aqueous solution (3mol/L) dropwise into the flask containing cyclic adenosine monophosphate. Control the temperature during the process. After the dropwise addition, the temperature is raised to room temperature. Use HCl solution (20%) adjust pH to 7~8, add absolute ethanol to precipitate a white solid, filter through Rohm and Haas resin, and dry to obtain a white solid sodium salt; heat the sodium salt and n-butyric anhydride to 140 under N2 protection ℃ reaction, TLC monitoring, after the reaction is completed, it is lowered to room temperature, methyl tert-butyl ether is slowly added, and the process is stirred vigorously to obtain a nearly white solid crude product. Resuspend the mixed solution of methyl tert-butyl ether and acetone to obtain the target product as white powder.
Method 2: A preparation method of sodium dibutyryl cyclic adenosine monophosphate, including the following steps:
(1) Take the test samples of sodium butyryl cyclic adenosine monophosphate, sodium dibutyryl cyclic adenosine monophosphate, and acetonitrile of cyclic adenosine monophosphate, which are chromatographically pure, and the water is redistilled water for later use. The above raw materials are all commercially available;
(2) Slowly add 3-5 mol/L sodium hydroxide aqueous solution dropwise into the flask containing cyclic adenosine monophosphate, control the temperature during the process, and raise the temperature to room temperature after the dropwise addition is completed;
(3) Adjust the pH to 7-12 with 20% HCl solution, add absolute ethanol to precipitate a white solid;
(4) Filter and dry to obtain white solid sodium salt;
(5) Heat the sodium salt and n-butyric anhydride to 140 degrees Celsius under N protection, and monitor with TLC. After the reaction is complete, return to room temperature;
(6) Slowly add methyl tert-butyl ether and stir vigorously during the process to obtain a nearly white solid crude product;
(7) Resuspend the mixed solution of methyl tert-butyl ether and acetone to obtain a white powdery product, which is obtained.
Main reference materials
[1] Preparation of dibutyryl cyclic adenosine monophosphate sodium and its content and determination of related substances
[2] CN201611122251.2 Preparation method of dibutyryl cyclic adenosine monophosphate sodium
[3] Determination and correlation of the solubility of dibutyryl cycloadenosine sodium in water-acetone mixed solvent
