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

"One-pot" preparation of macrolides mediated by alkyne amides

A technology of macrocyclic lactone and alkyne amide, which is applied in the preparation of sulfonic acid amide, organic chemical methods, peptides, etc., to achieve the effect of realizing application value and direct and simple synthesis

Active Publication Date: 2021-12-14
广州新肽生物医药科技有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this strategy involves the catalysis of the noble metal palladium at high temperatures.
In 2015, the Bi research group found that the addition of carboxylic acid and alkyne amides can be carried out without metal catalysis, but the reaction must be carried out at a high temperature of 100°C, and some compounds that are unstable under high temperature conditions cannot be prepared by this method ( Green Chemistry 2015,17,184-187)

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
  • "One-pot" preparation of macrolides mediated by alkyne amides
  • "One-pot" preparation of macrolides mediated by alkyne amides
  • "One-pot" preparation of macrolides mediated by alkyne amides

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0037]

[0038] In a clean 4mL reaction flask, add alkyne amide (0.22mmol), 7-hydroxyheptanoic acid (0.2mmol), add catalyst 10mmol% CuCl, add 2mL CH 2 Cl 2 It was used as a solvent and reacted at room temperature for 24 hours, followed by TLC plate detection. After the reaction, the solvent was concentrated and column chromatography was used to obtain a pure product, a white solid, with a yield of 92%.

[0039] 1 H NMR (400MHz, CDCl 3 )δ7.7(dd,2H),7.3(dd,J=12.7,7.0Hz,2H),4.8(d,1H),4.6(d,1H),3.6(t,2H),3.0(s,3H ),2.4(s,3H),2.3(t,2H),1.7–1.5(m,4H),1.4–1.3(m,4H).

[0040] 13 C NMR (101MHz, CDCl 3 )δ171.1, 147.1, 144.1, 133.9, 129.5, 128.0, 100.3, 62.7, 37.4, 33.8, 32.5, 28.7, 25.3, 24.4, 21.5.

[0041] HRMS m / z(ESI)calculated for C 17 h 25 NaNO 5 S+(M+) + :356.1346, found: 378.1342

example 2

[0043]

[0044] In a clean 4mL reaction tube, add alkyne amide (0.22mmol), 12-hydroxyalkanoic acid (0.2mmol), add 10mol% CuI, add 2mL CH 2 Cl 2 It was used as a solvent and reacted at room temperature for 24 hours, followed by TLC plate detection. After the reaction, the solvent was concentrated and column chromatography was used to obtain a pure product, a white solid, with a yield of 93%.

[0045] 1 H NMR (400MHz, CDCl 3 )δ7.72(dd, J=8.1Hz, 2H), 7.32(dd, J=8.0Hz, 2H), 4.81(s, 1H), 4.62(s, 1H), 3.63(t, J=6.6Hz, 2H), 3.01(s, 3H), 2.44(s, 3H), 2.31(t, 2H), 1.65–1.11(m, 20H).

[0046] 13 C NMR (101MHz, CDCl 3 )δ171.3, 147.0, 144.0, 133.9, 129.5, 128.0, 100.5, 63.0, 37.3, 33.9, 32.8, 29.5, 29.5, 29.4, 29.4, 29.2, 29.0, 25.7, 24.5, 21.6.

[0047] HRMS m / z(ESI)calculated for C 22 h 35 NNaO 5 S+(M+) + :448.2128, found: 448.2127

example 3

[0049]

[0050] In a clean 4mL reaction tube, add alkyne amide (0.20mmol), 12-hydroxyalkanoic acid (0.2mmol), add 10mol% CuCl, add 2mL CH 2 Cl 2 It was used as a solvent and reacted at room temperature for 24 hours, followed by TLC plate detection. After the reaction was completed, the solvent was concentrated and column chromatography was used to obtain a pure product, a white solid, with a yield of 91%.

[0051] 1 H NMR (400MHz, CDCl 3 )δ7.72(s, 2H), 7.31(dd, 2H), 4.81(d, J=2.4Hz, 1H), 4.63(d, J=2.3Hz, 1H), 3.63(t, 2H), 3.01( s,3H),2.44(s,3H),2.31(t,2H),1.70–1.03(m,24H).

[0052] 13 C NMR (101MHz, CDCl 3 )δ 171.3, 147.0, 144.0, 134.0, 129.0, 128.0, 100.5, 63.0, 37.3, 34.0, 32.8, 29.6, 29.6, 29.4, 29.4, 29.2, 29.0, 25.7, 24.5, 21.6.

[0053] HRMS m / z(ESI)calculated for C25H41NNaO5S+(M+) + :490.2598,found:490.2591

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 method for preparing macrocyclic lactones by using alkyne amides as condensation reagents and hydroxycarboxylic acids as raw materials under the condition of 10-50 degrees centigrade; A method for mildly and efficiently preparing α-acyloxyenamide compounds by amide addition; a method for obtaining macrolide by reacting intramolecular hydroxyl groups of α-acyloxyenamide compounds under the catalysis of p-toluenesulfonic acid; The above two reactions can be implemented as a "one-pot method", that is, the intermediate α-acyloxyenamide after the reaction of the carboxylic acid and the alkyne amide does not need to be separated, and is directly added to p-toluenesulfonic acid for the next step of intramolecular condensation reaction. The formation of alkynamide-mediated macrolides can be achieved at room temperature. The method of the invention is characterized in that the reaction conditions are mild, simple and easy to operate.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to a method for efficiently preparing long-chain alkyl α-acyloxy enamide activated esters at room temperature and under the catalysis conditions of cheap metal CuI, CuCl or CuCN, and also relates to long-chain alkyl A high-efficiency macrolactonization method of α-acyloxyenamide activated esters without dimerization under the catalysis of p-toluenesulfonic acid. Background technique [0002] Macrolide is a very important structure in natural products and drug molecules. It was Kerschbaum (Kerschbaum, M.Chem.Ber.1927, 60, 907) who isolated the 16-ring lactone Exaltlide for the first time in 1927, and then he Definition Macrolide refers to a compound with more than 8 atoms in the ring, such as octalactins with 8-membered rings (Tapiolas, D.M.; Roman, M.; Fenical, W.; Stout, T.J.; Clardy, J.J.Am.Chem.Soc. 1991, 113, 4682). Many macrolide antibiotics have significant curative effects....

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): C07C303/40C07C311/17C07D313/18C07D313/00C07D321/00C07D267/00C07K5/062C07K5/083
CPCC07C303/40C07D267/00C07D313/00C07D313/18C07D321/00C07K5/06026C07K5/0806C07B2200/07C07C311/17
Inventor 赵军锋杨明王雪伟
Owner 广州新肽生物医药科技有限公司
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