With the improvement of people's living standards and the increasingly serious global aging problem, the world's pursuit of anti-aging drugs is becoming more and more intense. As a key intermediate in the NAD+ salvage synthesis pathway, β-NMN has shown amazing potential in anti-aging, it can effectively enhance the metabolism in the organism and prolong the lifespan of the living body. At the same time, it also shows good results in the treatment of some elderly diseases such as stroke, Alzheimer's disease, Parkinson's disease, type 2 diabetes, etc. Although the role of β-NMN in the human body needs further study, it provides a feasible direction for the research and development of anti-aging drugs and health care products and provides a potential treatment for neurodegenerative diseases caused by aging.
How is nmn manufactured?
(1) Using tetra acetyl ribose and nicotinic acid ethyl ester as raw materials
Using tetra acetyl ribose and nicotinic acid ethyl ester as raw materials, condensation occurs under the condition of trimethylsilyl trifluoromethanesulfonate (TMSOTf) to generate compound 3, and then under the condition of sodium ethoxide, the acetyl group protection is removed to obtain compound 4, Phosphorylation was then performed with phosphorus oxychloride to obtain compound 5, and finally, aminolysis was performed with ammonia to obtain the target product NMN. In this route, the first two steps can obtain compound 4 without obvious impurities by NMR, and the yield is about 80%, and only the last step needs to be purified by ion exchange resin to remove inorganic salts, such as ammonium chloride, etc. After acidification to remove excess ammonia gas, NMN with HPLC purity above 97% can be obtained. The reaction raw materials of this route are easy to obtain, the reaction conditions are relatively low, and there is no need for purification during the routing process, which saves a lot of purification costs, and is suitable for industrial mass production needs.
(2) Using diphenyl chloroquine as a phosphorylation reagent
The first step is the esterification reaction. Using acetonitrile as solvent and pyridine as an acid-binding agent, compound 6 (β-nicotinamide ribose) was esterified with compound 7 (diphenyl chlorophosphate) to generate compound 8, which was used directly in the next step without purification after solvent removal; The second step is the hydrolysis reaction. The compound β-NMN was obtained by metal-catalyzed hydrogenation. After removing the catalyst and solvent, ion exchange was carried out. After resin purification, β-NMN with a purity of 99.3% was obtained, and the yield was about 64%. In this route, diphenyl chlorophosphate is used instead of highly toxic phosphorus oxychloride for phosphorylation, diphenyl chlorophosphate can be added quantitatively, the reaction selectivity is good, the yield and purity are greatly improved, and the oxygen trichloride is avoided at the same time. Phosphorus post-treatment will produce a large amount of waste acid water, and because no trimethyl phosphate solvent is used in the reaction process, post-treatment is simpler and more convenient.
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