Bionic synthesis and preparation method of (+/-)-isomacahydantoin B

A biomimetic synthesis, thiourea technology, applied in the direction of organic chemistry, can solve the problems of limited biological activity research, structural identification errors, lack and other problems, and achieve the effect of simple and efficient method.

Inactive Publication Date: 2017-12-15
YUNNAN MINZU UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the structure of (±)-macahydantoin B identified by Qiu et al. has the problem of structural identification errors, and the structure is identified as (±)-isomacahydantoin B, an analog of (±)-macahydantoin A, because (±)-isomacahydantoin B has a novel However, due to the lack of samples of (±)-isomacahydantoin B, its further biological activity research is limited. In

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Bionic synthesis and preparation method of (+/-)-isomacahydantoin B
  • Bionic synthesis and preparation method of (+/-)-isomacahydantoin B
  • Bionic synthesis and preparation method of (+/-)-isomacahydantoin B

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0032] The preparation method of (±)-isomacathiourea B is based on Boc-piperidin-3-one as the starting material for the reaction, followed by nucleophilic reaction with trimethylsilyl cyanide (TMSCN) catalyzed by zinc iodide Substitution reaction gives Boc-2-cyano-3-hydroxypiperidine (the first step reaction A), which is then hydrolyzed by concentrated hydrochloric acid to obtain 3-hydroxy-piperidine-3-carboxylic acid hydrochloride (the second step reaction B ), and finally by Edman reaction with 3-methoxybenzyl isothiocyanate to obtain (±)-isomacathiourea B (the third step reaction C). The yield of the three-step reaction route is as high as 60-70%, and it can be prepared in grams. The specific route is:

[0033]

[0034] (A) Preparation of Boc-2-cyano-3-hydroxypiperidine: Boc-piperidin-3-one (0.199~19.9 g, 1.0~100.0mmol) dissolved in 5~500 mL of anhydrous dichloromethane solution Under the protection of nitrogen, after fully stirring to dissolve, add zinc iodide (0.318~31.8 g,...

Example Embodiment

[0038] Example 1

[0039]

[0040] Boc-piperidin-3-one (0.398 g, 2.0 mmol) was dissolved in 10 mL of anhydrous dichloromethane solution under nitrogen protection. After stirring well to dissolve, add zinc iodide (0.636 g, 2.0 mmol) under ice bath conditions. ) And trimethylsilyl cyanide (0.396g, 3.0 mmol), and the reaction was stirred at room temperature for 6 hours. The reaction solution was filtered with a suction filter flask, the zinc iodide was filtered out, and then evaporated to dryness under reduced pressure with a rotary evaporator. After suction filtered under reduced pressure, it was dried in a vacuum drying oven for 12 hours to obtain Boc-2-cyano-3-hydroxypiper A sample of pyridine (0.566 g, purity about 80%), the yield is about 90%. The obtained Boc-2-cyano-3-hydroxypiperidine (0.258 g, 2.0 mmol) was dissolved in 15 mL of concentrated hydrochloric acid solution, and the reaction was refluxed at 85°C for 12 hours. The reaction solution was evaporated to dryness unde...

Example Embodiment

[0041] Example 2

[0042]

[0043] Boc-piperidin-3-one (1.990 g, 10.0 mmol) was dissolved in 50 mL of anhydrous dichloromethane solution, protected by nitrogen, and after it was fully stirred to dissolve, zinc iodide (3.180 g, 10.0 mmol) was added under ice bath conditions. ) And trimethylsilyl cyanide (1.980 g, 15.0 mmol), and the reaction was stirred at room temperature for 6 hours. The reaction solution was filtered with a suction filter flask, the zinc iodide was filtered out, and then evaporated to dryness under reduced pressure with a rotary evaporator. After suction filtered under reduced pressure, it was dried in a vacuum drying oven for 6 hours to obtain Boc-2-cyano-3-hydroxypiper The sample of pyridine (2.830 g, purity is about 80%), the yield is about 90%. The obtained Boc-2-cyano-3-hydroxypiperidine (1.290g, 10.0 mmol) was dissolved in 45 mL of concentrated hydrochloric acid solution, and the reaction was refluxed at 85°C for 12 hours. The reaction solution was evap...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a bionic synthesis and preparation method of (+/-)-isomacahydantoin B. The (+/-)-isomacahydantoin B is a derivative of a natural alkaloid (+/-)-macahydantoin A found in a medicinal plant maca, uses biogenic precursors benzyl isothiocyanate and 3-hydroxyl-piperidine-3-carboxylic acid as raw materials and is an artificially synthesized natural product-like compound obtained through biomimetic synthesis based on a 'one-pot method'. The (+/-)-isomacahydantoin B is structurally characterized by consisting of a 1,3-diazabicyclo[3.3.1]nonane parent nucleus and a 3-hydroxybenzyl substituted group, and a chemical structure is shown in the description. The bionic synthesis and preparation method uses Boc-piperidine-3-ketone as a starting material for reaction, nucleophilic substitution reaction is performed between the starting material and zinc iodide catalyzed trimethylsilyl cyanide (TMSCN) to obtain Boc-2-cyano-3-hydroxyl piperidine, and then 3-hydroxyl-piperidine-3 carboxylic acid hydrochloride is obtained through hydrolysis with concentrated hydrochloric acid; the (+/-)-isomacahydantoin B is obtained through Edman reaction with 3-methoxyl benzyl isothiocyanate. The synthesis method is simple and efficient, and gram-level preparation of the compound can be achieved.

Description

technical field [0001] The invention belongs to the technical field of compound synthesis, and in particular relates to a biomimetic synthesis preparation method of (±)-isomacathiourea B. Background technique [0002] Maca (Latin name Lepidium meyenii Walp), a 1-2-year-old herbaceous medicinal plant of the genus Brassicaceae, native to the Andes in South America (3500-4500 altitude above sea level), is a commonly used medicinal plant and edible material in the local area, known as "Peruvian ginseng". . It was introduced in my country in early 1990, among which Lijiang and Shangri-La in Yunnan are the main planting areas. At the same time, it is also widely planted in Huize, Zhaotong, Yuxi and other areas in Yunnan. Qiu et al. have studied the chemical composition and biological activity of the plant and found that the The plant contains a novel sulfur-containing alkaloid (±)-macahydantoins A and B with a 1,3-diazabicyclo[3.3.1]nonane skeleton, suggesting that this component...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D471/08
CPCC07D471/08
Inventor 叶艳青陈彦君周敏耿慧春张芮绮胡秋芬
Owner YUNNAN MINZU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap