Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of preparation method of acetonyl geranyl pyrophosphate intermediate

An oxidation system, iodoyl benzoic acid technology, applied in the field of medicine and chemical industry, can solve problems such as configuration impurities

Active Publication Date: 2022-08-05
CHONGQING PHARMA RES INST +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The object of the present invention is to provide a method for the intermediate VI of acetonylgeranyl pyrophosphate shown in formula X, which overcomes the problems in the prior art, such as the use of highly toxic selenium dioxide, easy oxidation of the structure problems such as type impurities, the method of the present invention is simple to operate, practical, low cost, high yield and environmental protection, raw materials are easy to get, post-processing is simple, suitable for large-scale industrial production

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
  • A kind of preparation method of acetonyl geranyl pyrophosphate intermediate
  • A kind of preparation method of acetonyl geranyl pyrophosphate intermediate
  • A kind of preparation method of acetonyl geranyl pyrophosphate intermediate

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0072] Benzoyl-protected hydroxyaldehydes 21

[0073]

[0074] Step 1 Preparation of acacia benzoate 11

[0075] Farnesol (15.0 g, 67 mmol) was dissolved in 120 ml of pyridine, cooled at low temperature to keep the inner temperature below 0 °C, benzoyl chloride (11.4 g, 81 mmol) was added dropwise, and the mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with water, then extracted with petroleum ether three times, the petroleum ether layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated and purified by column chromatography to obtain 20.1 g of the product with a yield of 90%.

[0076] Step 2 Preparation of epoxide 12

[0077] The farnesyl benzoate (20.0 g, 61 mmol) obtained in the previous step was dissolved in 240 ml of tetrahydrofuran, 120 ml of water was added, the internal temperature was kept below 0 °C by low temperature cooling, and N-bromosuccinimide ( NBS) (12.0 g, 67.4 mm...

preparation example 2

[0084] p-Methoxybenzyl (PMB) protected hydroxyaldehyde 24

[0085]

[0086] Step 1 Preparation of Acacia p-methoxybenzyl ether 9

[0087] Dissolve farnesol (5.0 g, 22.5 mmol) in 50 ml of N,N-dimethylformamide, cool at low temperature to make the inner temperature below 0 °C, add 60% sodium hydrogen (1.8 mg, 45 mmol), stir for 0.5 hour After that, p-methoxybenzyl chloride (PMBCl) (5.3 g, 34 mmol) was added dropwise, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with water, then extracted with petroleum ether three times, the petroleum ether layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated and purified by column chromatography to obtain 7.1 g of the product with a yield of 92%.

[0088] Step 2 Preparation of Epoxide 10

[0089] The farnesol p-methoxybenzyl ether (7.0 g, 20.4 mmol) obtained in the previous step was dissolved in 80 ml of tetrahydrofuran, 40 ml of water wa...

preparation example 3

[0094] tert-Butyldiphenylsilyl (TBDPS) protected hydroxyaldehyde 18

[0095]

[0096] Step 1 Preparation of Acacia pure TBDPS ether 7

[0097] Dissolve farnesol (10.0 g, 45.0 mmol) in 100 ml of dichloromethane, cool at low temperature to keep the internal temperature below 0 °C, then add tert-butyldiphenylchlorosilane (TBDPS) (16.0 g, 58.5 mmol), Then imidazole (5.0 g, 67.5 mmol) was added in portions, the addition was complete, the cooling bath was removed, and the mixture was stirred at room temperature for 1 hour. The reaction solution was washed successively with 100 ml of water and 100 ml of saturated aqueous sodium chloride solution. The dichloromethane layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 24.3 g of a light yellow transparent liquid, which was directly used in the next reaction.

[0098] Step 2 Preparation of Epoxide 8

[0099] Dissolve the farnesol TBDPS ether (24.3 g, 45 mmol) obtained in the pre...

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 provides a method for preparing an intermediate of acetonyl geranyl pyrophosphate. Farnesol is used as a raw material, hydroxyl group is protected, and then an epoxy intermediate is prepared, which is cut by epoxy to form an aldehyde, and then mixed with methyl Grignard reagent. Reaction, re-oxidation of hydroxyl group, deprotection to obtain (5E, 9E)-11-hydroxyl-5,9-dimethylundec-5,9-dien-2-ketone 7, then hydroxy halogenation, then with pyrophosphoric acid A salt reaction is performed to finally obtain acetonyl geranyl pyrophosphate. The method is cheap to synthesize, has mild reaction conditions, and has less isomer impurities, and is suitable for scale-up production.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a new method for an intermediate of acetonyl geranyl pyrophosphate. Background technique [0002] Antibody-drug conjugates (antibody-drug conjugates, ADCs) are a class of drugs that couple anti-cancer agents to antibodies. Compared with traditional therapeutic drugs, ADCs can improve the therapeutic effect of antibody drugs, overcome drug resistance and fully Take advantage of the unique advantages of antibody targeting. The main structure of ADCs includes three parts: antibody, high-efficiency cytotoxic drug, and linker. A series of ADC compounds (structural formula 1) developed by South Korea's Legochem Biosciences, INC. have high drug activity (WO 2016 / 108587) and can be used for the development of breast cancer, gastric cancer and other tumor fields. From the analysis of its compound structure, the coupler of ADC uses acetonyl geranyl pyrophosphate (structural ...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07C45/64C07C49/24C07C45/63C07C49/227C07F9/113C07F7/18C07C69/78C07C43/23C07C43/178C07C49/255
CPCC07C41/30C07C43/178C07C43/23C07C45/29C07C45/292C07C45/63C07C45/64C07C49/255C07C67/29C07C67/293C07C69/78C07F7/1892C07F9/113C07C49/24C07C49/227Y02P20/55
Inventor 徐立炎雷文波刘启万周昌兵万咏清袁泉
Owner CHONGQING PHARMA RES INST
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com