Alkyne amide-mediated one-pot method for preparing macrolide

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

Active Publication Date: 2018-10-12
JIANGXI NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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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

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  • Alkyne amide-mediated one-pot method for preparing macrolide
  • Alkyne amide-mediated one-pot method for preparing macrolide
  • Alkyne amide-mediated one-pot method for preparing macrolide

Examples

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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

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Abstract

The invention discloses a method for preparing macrolide by using alkyne amide as a condensation reagent and hydroxy carboxylic acid as a raw material at 10-50 DEG C; the method comprises a method formildly and efficiently preparing an alpha-acyloxy alkenyl amide compound through addition of carboxylic acid and alkyne amide at room temperature under the catalysis of cuprous salt and a method forobtaining macrocyclic lactonization through enabling the intramolecular hydroxyl of the alpha-acyloxy alkenyl amide compound to react under the catalysis of p-toluenesulfonic acid; the two reactions can be performed through a one-pot method as well, i.e., an intermediate alpha-acyloxy alkenyl amide obtained after complete reaction of carboxylic acid and the alkyne amide does not need to be separated, the p-toluenesulfonic acid is directly added to perform intramolecular condensation reaction in the next step, thereby realizing the formation of the alkyne amide-mediated macrocyclic lactonization at room temperature. The method disclosed by the invention has the characteristics of mild reaction condition, simplicity and easy operation.

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

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Application Information

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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 JIANGXI NORMAL UNIVERSITY
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