Green technology solves the problem of pharmaceutical environmental protection



Where there is green, there is life. In the awareness of the importance of environmental protection and sustainable development, the pursuit of "green development" has become an irresistible new trend of the present, how to use green technology to solve the environmental problems of the pharmaceutical industry, has become an urgent problem for China's pharmaceutical companies to solve.

12 Principles of Green chemistry

Green chemistry, also known as environmentally friendly chemistry or sustainable chemistry, is a widely accepted definition developed by chemists Paul Anastas and John C. Warner, which refers to the design of chemical products and processes that reduce or avoid the use and production of harmful substances. The two scientists also pioneered the 12 principles of green chemistry, It is to prevent environmental pollution, improve atomic economy, minimize toxic raw materials and toxic products in chemical synthesis, design safe chemicals, use safe solvents and auxiliaries, improve energy economy, reuse of raw materials, introduction of less functional groups, development of new catalysts, easy degradation of products, on-site practical analysis to reduce environmental pollution and prevent production Therefore, the safe production process. The 12 principles of green chemistry provide the basis and standard for judging whether a synthetic route, a production process and a compound are "green".

A classic example of compliance with the 12 principles of green chemistry is the 2005 Nobel Prize in Chemistry. Three scientists from France and the United States have discovered a catalytic reaction process of olefin metathesis, that is, two olefins can generate two new olefins under the action of a catalyst, and this discovery is regarded as a novel and effective new method to form a carbon-carbon double bond skeleton. This reaction has become a common method in the chemical industry, especially the pharmaceutical industry and the materials industry, because it is more effective, easy to operate and more beneficial to the environment.

Modern green pharmaceutical technology

Green chemistry holds great promise in the pharmaceutical field. Through the application of advanced means to reduce the discharge of "three wastes" (wastewater, exhaust gas, waste residue) for environmental protection purposes, the modernization level of the pharmaceutical industry can be greatly improved, while achieving environmental sustainable development.

Catalysis is an important phenomenon in nature, and the application of catalyst can change the rate of chemical reaction. Data show that about 90% of chemical products are produced with the help of catalytic processes. In recent years, in addition to traditional catalysts, biocatalysts have increasingly attracted the attention of pharmaceutical companies, and may become the first choice to replace transition metal catalysts. For example, GlaxoSmithKline and Merck are using biocatalysis technology to mass-produce kilogram drug formulations and apply the technology to the entire drug development process from drug discovery to the clinical trial stage and the final product to market. The use of enzyme technology can also rapidly synthesize complex drug molecules that are not easily manufactured by conventional organic chemistry, thus providing more drug candidates for the early stages of drug discovery.

Continuous reaction technology After several years of development, continuous reaction technology has been transformed from a niche academic application research into a recognized industrial technology, with the advantages of safety, efficiency, high quality and low cost. The continuous reaction technology can be flexibly adjusted according to the specific reaction process and target, which can adapt to the reaction under the small scale and can meet the large-scale industrial production. According to a report by Green Chemistry, nearly 50 European pharmaceutical companies have chosen to use continuous reaction technology, mainly because of its high safety, environmental friendliness and product quality.

Organic mechatronics synthesis and photochemical synthesis by electrochemical method is called organic mechatronics synthesis, which is widely used in the production of organic chemical industry. In fact, electromechanical synthesis technology has experienced a long history of more than 170 years, so it is called "old method, new technology". The nature of organic synthesis is based on electrolysis to synthesize organic compounds, and the reaction is completed by the gain and loss of electrons on the electrode, which has the characteristics of clean energy and green environmental protection. Similar to it is the wonderful organic photochemical synthesis technology, the basic principle is that the reactant molecule absorbs light energy and transitions from the ground state to the excited state, becoming an activated molecule, and then triggering a chemical reaction. Organic photochemical synthesis technology is one of the most active and flourishing technologies in the field of synthetic chemistry, which has the advantages of cleanliness, energy saving and various reaction types.

In addition, modern green pharmaceutical technology also includes the following: can control chemical reactions, improve the precision of pharmaceutical technology; Microwave technology that can increase the rate and efficiency of chemical reactions and increase drug production; Supercritical fluid technology (SCF) can replace organic solvents with high toxicity and play the role of medium, so it has high application value.

Pharmaceutical industry application scenarios

In the pharmaceutical industry, the production of semi-synthetic ampicillin and amoxicillin can be applied to the green new enzyme reaction.

In the traditional synthesis process, the active hydrogen in penicillin G is first protected by silyl substitution, and then reacts with phosphorus pentachloride to form chlorimide ester at -40℃, and then hydrolyzed to obtain 6-APA, an important raw material for semi-synthetic penicillin.

However, this reaction has been largely replaced by a new enzymatic reaction of penicillin G acyltransferase, which can react in water slightly above room temperature and does not require a silyl protective group. According to statistics, at present, a large number of 6-APA is manufactured by a more environmentally friendly enzymatic process every year, which has become a representative case of the successful application of green chemistry in the pharmaceutical field.

Another example of a catalytic reaction is the third-generation biocatalytic aminotransferase process formed by Merck through an improved process in the production of sittalliptin. Compared to the second generation technology, the third generation process is more in line with the green manufacturing concept of safety, atomic economy, waste prevention and energy saving. The technology avoids the use of the toxic metal rhodium, eliminates the need for high pressure, high temperature hydrogenation, and replaces it with a process that operates at room temperature and pressure, making the production process safer, lower energy consumption, and lower costs.

It is worth mentioning that biocatalytic aminotransferases are often engineered enzymes that have been "evolved" and modified by biotechnology, and can be directed to the synthesis of products that meet purity needs, while transition metal catalysts usually do not have this highly customized. According to statistics, at present, 25% to 75% of the global pharmaceutical companies in the research and development pipeline have applied biocatalysis technology.

Roche also considers the green chemistry principle in the synthesis of pyridinium and imidazoles. The original synthesis route involved 3-amino-pentane-1, 5-diol, which was highly water-soluble and difficult to separate and extract from the aqueous reaction mixture, requiring a large amount of dichloromethane. By streamlining and improving the process, the company began the reaction with a more readily available and inexpensive compound, used a single solvent that was easier to recover and recycle, and finally purified 3-aminopentane-1, 5-diol using an acid resin under non-aqueous conditions, resulting in a total yield of 89% and an API purity of 99.5%.

Green chemical pharmaceutical technology is related to economic benefits, social benefits and environmental benefits, and is of great significance to ecological sustainable development and improvement of human life quality. To this end, global pharmaceutical companies should continue to innovate, develop and adopt more green pharmaceutical technologies for the benefit of society.