Pharmaceutical intermediates: the future development of adenine

Adenine, also known as 6-aminopurine, has a chemical formula of C5H5N5. It is a fused ring system composed of pyrimidine and imidazole rings. Adenine in organisms is mainly synthesized from amino acids and small molecules as starting materials through a series of enzymatic reactions.

However, adenine is not only an important part of DNA and RNA in organisms, but also as a pharmaceutical intermediate for the production of antiviral drugs, Plant Growth Regulators, etc., and its usage has been increasing worldwide in recent years.

Adenine is mainly produced by microbial fermentation

At present, the production methods of adenine mainly include chemical synthesis, natural raw material extraction and microbial fermentation.

The chemical synthesis method mainly refers to the acetyl hypoxanthine method. Firstly, acetylhypoxanthine and phosphorus oxychloride undergo chlorination reaction under catalyst conditions to obtain 6-chloropurine; then in the autoclave, 6-chloropurine is blown with Ammonia to saturation, the reactor is sealed, and the temperature is increased Until the reaction is complete, adenine is precipitated after cooling. In addition to the acetyl hypoxanthine method, there are other chemical synthesis process routes, but the yields are low, and the reaction time is long and the reaction conditions are harsh. The acetyl hypoxanthine method uses phosphorus oxychloride to produce a large amount of waste liquid, and subsequent environmental protection treatment is difficult.

The natural raw material extraction method mainly extracts adenine enriched in natural substances, but this method has low yield and high cost, and is not suitable for industrial production.

The microbial fermentation method has mild production conditions, simple process, and reaction conversion rate of over 99%, which is conducive to industrial production. The specific process is as follows: Adenosine is hydrolyzed by hydrolase to generate adenine and D-ribose. Mix adenosine and water, adjust the pH of the reaction system to 6.5-7.0, add adenosine hydrolase, heat up to 35-37°C and keep warm and react; after the reaction is completed, solid-liquid separation is performed, and the liquid phase is concentrated to obtain D-ribose. Solid phase washing obtains adenine.