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Preparation method of S-nicotine

A nicotine and amino acid technology, applied in the field of S-nicotine preparation, can solve the problems of high environmental and safety costs, expensive chemical catalysts, and short overall routes, and achieve low production costs, low prices, and wide sources of raw materials.

Active Publication Date: 2021-11-09
SHENZHEN READLINE BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the route is relatively short and the yield is high, the production cost is high due to the use of expensive mysmin as the starting material
[0009] The above three classic S-nicotine preparation techniques can be concluded that although the two chemical preparation methods of route I and route II also use relatively cheap raw materials, the overall route is also Not long (three- or four-step reaction), but the chemical catalysts involved in the reaction are expensive (BF3, LDA, NaBH4), dangerous to operate (LDA, NaCN ) and other factors lead to high environmental and safety costs in its large-scale production
Route III uses mesmin as a raw material, utilizes imine reductase chiral reduction to obtain S-nornicotine (nornicotine), and then uses chemical methods to carry out methylation; the defect of this route is that it needs to use expensive mesmin as Raw materials, thus greatly increasing the overall production cost

Method used

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  • Preparation method of S-nicotine
  • Preparation method of S-nicotine
  • Preparation method of S-nicotine

Examples

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preparation example Construction

[0078] The invention provides a preparation method of S-nicotine. Those skilled in the art can refer to the content of this article to appropriately improve the process parameters to achieve. In particular, it should be pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the method and application herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention Invent technology.

[0079] Unless otherwise specified, the test materials used in the present invention are all common commercial products, which can be purchased in the market.

[0080] In the present invention, catalase (catalase) was purchased ...

Embodiment 1

[0085] Example 1 One-pot method for preparing S-nicotine by liquid enzyme (AO1, NS)

[0086] Add 17 g of 1-methylpyrrolidine (200 mM), 24.6 g of nicotinic acid (200 mM), and 3.0 g of β-nicotinamide adenine into 1 L of 50 mM pH 8.0 tris-hydrochloride (Tris.HCl) solution dinucleotide phosphate (NADP +) monosodium salt (0.4mM), 52 grams of sodium phosphite pentahydrate (240mM) and 100ml of isopropanol (substrate co-solvent). Utilize NaOH aqueous solution to adjust the pH value of the reaction solution to 8.0, add the compound enzyme to obtain the reaction solution; wherein, the compound enzyme is composed of: 2000UAO1 (SEQ ID NO:1), 4000UNS (SEQ ID NO:5), 1000U Catalase, 6000U PTDH ( SEQ ID NO: 7);

[0087] Subsequently, the reaction solution was transferred to a pressure-resistant reactor to maintain an oxygen pressure of 1.5 atmospheres at 30° C. and slowly stirred for 6 hours. After the reaction, the pH of the solution was adjusted to 10 and extracted three times with 700 ml...

Embodiment 2

[0088] Embodiment 2: liquid enzyme (AO2, NS) prepares S-nicotine in one pot

[0089] The difference from Example 1 is that the amino oxidase AO2 replaces AO1, and the other processes are the same. Similarly, 17 grams of 1-methylpyrrolidine (200 mM), 24.6 grams of nicotinic acid (200 mM), and 3.0 grams of β-nicotinamide gland Purine dinucleotide phosphate (NADP + ) monosodium salt (0.4mM), 52 grams of sodium phosphite pentahydrate (240mM) and 100ml of isopropanol. Utilize NaOH aqueous solution to adjust the pH value of the reaction solution to 8.0, add the compound enzyme to obtain the reaction solution; wherein, the compound enzyme is composed of: 2000UAO (SEQ ID NO:2), 4000UNS (SEQ ID NO:5), 1000U Catalase, 6000UPTDH ( SEQ ID NO: 7);

[0090] Subsequently, the reaction solution was transferred to a pressure-resistant reactor to maintain 1.5 atmospheric pressure of oxygen at 30° C. and stirred for 4 hours. After the HPLC detection reaction was completed and the pH of the so...

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Abstract

The invention relates to the technical field of biosynthesis, in particular to a preparation method of S-nicotine. According to the invention, amine oxidase is creatively utilized to oxidize 1-methylpyrrolidine into corresponding imine, and then the imine and nicotinic acid are condensed and decarboxylated under the catalysis of nicotine synthetase to obtain the final product S-nicotine. According to the method, the S-nicotine with specific chirality can be obtained through two-step reaction in a reaction system, the synthetic route is short, the yield is high, the reaction conditions are mild, and large-scale production is easy to realize; and meanwhile, the raw materials are wide in source, low in price, low in production cost and environmentally friendly, the production cost of nicotine is remarkably reduced, and the nicotine better meets the requirements of current green industrial production at the same time.

Description

technical field [0001] The invention relates to the technical field of biosynthesis, in particular to a preparation method of S-nicotine. Background technique [0002] Nicotine is an important component in tobacco, and it is also the core raw material for e-cigarette formulations and the synthesis of certain nicotine drugs. [0003] The traditional tobacco leaf cultivation, extraction, and purification methods occupy a large area and take a long time, and because the extraction inevitably contains other highly toxic costs, it will cause great harm to the human body. Therefore, the direct synthesis of chemical or biological processes has become an important way for the preparation of S-nicotine. [0004] Several common S-nicotine preparation methods: [0005] [0006] Route I: Preparation of racemic nicotine by chemical method. Using pyridine acetaldehyde as a raw material, a nicotine racemate is prepared through three-step chemical reactions, and then chiral resolution...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N9/06C12N9/08C12N9/02C12N9/00C12N15/53C12P17/16
CPCC12N9/0022C12N9/0065C12N9/0004C12N9/00C12P17/165C12Y104/03006C12Y111/01006C12Y120/01001C12Y104/03004C12P17/12
Inventor 赵弘凌瑞枚付琳于铁妹潘俊锋刘建
Owner SHENZHEN READLINE BIOTECH CO LTD
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