Synthesis method of nicotinamide chloride ribose

Abstract

The invention relates to a synthesis method of chloridized nicotinamide ribose, which comprises the following steps: by taking tetraacetyl ribose as a raw material, activating the tetraacetyl ribose by adopting trimethylsilyl trifluoromethanesulfonate of which the amount is twice that of the tetraacetyl ribose, synthesizing trifluoromethanesulfonic acid acetyl nicotinamide ribose, deprotecting by using sulfuric acid, exchanging trifluoromethanesulfonic acid ions by using triethylamine tartrate, and synthesizing the chloridized nicotinamide ribose by using trimethylsilyl trifluoromethanesulfonate to obtain the chloridized nicotinamide ribose. And finally, reacting with soluble chlorine salt to exchange hydrogen tartrate into chloride ions to synthesize nicotinamide ribose chloride. According to the method, trimethylsilyl trifluoromethanesulfonate is adopted as an activating reagent of nicotinamide, and a sulfuric acid methanol solution is adopted as a deacetylation reagent, so that the high conversion rate of tetraacetyl ribose and the high yield of beta isomer are kept, and the production cost of nicotinamide chloride ribose is reduced. The method is high in yield, low in cost and good in stereoselectivity, residues of ions such as bromide ions and trifluoromethanesulfonate ions harmful to the human body are avoided, and the quality of the chloridized nicotinamide ribose product obtained through a chemical synthesis method is improved.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing nicotinamide ribose chloride. Background technique [0002] Nicotinamide riboside chloride (NR for short) is a derivative of nicotinamide, which can increase the content of nicotinamide adenine dinucleotide (NAD+) in human cells after taking it, so it has a good anti-aging effect. Currently, there are three methods for synthesizing NR using tetraacetylribose as a raw material that have been disclosed: [0003] [0004] Wherein the highest yield of β isomer obtained by method A is only about 45%, and because the ribose chloride is very unstable, it is easy to decompose; the hydrogen chloride produced in the production process corrodes the equipment seriously, and the production is difficult; Acetyl ribose is brominated, and then nicotinamide is applied. Although the yield of β-isomers increases when nicotinamide is applied, the b...

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Problems solved by technology

[0004] Wherein the highest yield of β isomer obtained by method A is only about 45%, and because the ribose chloride is very unstable, it is easy to decompose; the hydrogen chloride produced in the production process corrodes the equipment seriously, and the production is difficult; Acetyl ribose is brominated, and then nicotinamide is applied. Although the yield of β-isomers increases when nicotinamide is applied, the bromide ion in the brominated nicotinamide ribose molecule is harmful to the human body after being taken in large quantities. There is a large amount of residues when forming chloride ions, which affects the quality of the finally obtained NR product; Method C uses an excessive amount of trimethylsilyl trifluoromethanesulfonate to activate tetraacetylribose, making it high yield, high stereoselective and Niacinamide reaction (obtaining β isomer) and deprotection of acetyl group at the same time can synthesize trifluoromethanesulfonated nicotinamide ribose in one step, and then replace trifluoromethanesulfonate with chloride ion by ion exchange, but this method needs to use to a seven-fold excess of expensive trimethylsilyl trifluoromethanesulfonate relative to niacinamide, and because trifluoromethanesulfonic acid is a strong organic acid, the subsequent ion exchange process cannot remove the toxic trifluoromethanesulfonate completely removed, which also affects the quality of the final NR product

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