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Method for synthesizing alkaloid

A synthetic method and alkaloid technology, applied in the direction of organic chemistry, etc., can solve the problems of poor reaction regioselectivity, harsh conditions, and lengthy steps, and achieve the effects of good chemical regioselectivity, mild reaction conditions, and easy availability of raw materials

Inactive Publication Date: 2009-06-03
NANJING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] From the synthesis methods summarized above, it can be seen that: (1) high temperature pyrolysis ring closure reaction or Diels-Alder ring formation reaction from indene structure substrates face harsh conditions, low yield and poor reaction regioselectivity (usually accompanied by by-products 2 -Methyl-5H-indeno[1,2-b]pyridine) and other shortcomings; (2) the synthesis of Onychine from substituted pyridine requires strong acid and strong base conditions, and the source of substrates is limited; (3) the use of chain bottom The step-by-step method of forming rings is tedious, and the synthesis efficiency is not high

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  • Method for synthesizing alkaloid
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  • Method for synthesizing alkaloid

Examples

Experimental program
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Embodiment 1

[0023] Example 1: Synthesis of 4-methyl-5H-indeno[1,2-b]pyridine

[0024] Indenone (1.0mmol), 2-butyn-1-amine (2.0mmol) and 2.0mL absolute ethanol were contained in a single-necked bottle, and NaAuCl was added under stirring at room temperature 4 2H 2 O (0.05 mmol). Then the temperature was raised to reflux for 12 hours. Concentrate under reduced pressure to remove the solvent ethanol; add 10 mL of 6.0 M hydrochloric acid to the concentrated solution, and extract the solution with ether (10 mL×2). Then add 50% sodium hydroxide solution to the aqueous solution to adjust the pH value of the system to about 9. Then it was extracted with ether (10 mL×3), and the organic phases were combined. After washing with water and drying (Na 2 SO 4 ),concentrate. The concentrated solution was purified by column chromatography (silica gel; ethyl acetate / petroleum ether: 1 / 8) to obtain 90 mg of solid 4-methyl-5H-indeno[1,2-b]pyridine with a yield of 50%. mp90-92℃; 1 H NMR (300MHz, CDC...

Embodiment 2

[0025] Example 2: Synthesis of 4-methyl-5H-indeno[1,2-b]pyridine

[0026] Indenone (1.0mmol), 2-butyn-1-amine (2.0mmol) and 2.0mL absolute ethanol were contained in a single-necked bottle, and PtCl was added under stirring at room temperature 2(0.1 mmol). Then the temperature was raised to reflux for 10 hours. Concentrate under reduced pressure to remove the solvent ethanol; add 10 mL of 6.0 M hydrochloric acid to the concentrated solution, and extract the solution with dichloromethane (10 mL×2). Then add 50% sodium hydroxide solution to the aqueous solution to adjust the pH value of the system to about 9. Then it was extracted with dichloromethane (10 mL×3), and the organic phases were combined. After washing with water and drying (MgSO 4 ),concentrate. The concentrated solution was purified by column chromatography (silica gel; ethyl acetate / petroleum ether: 1 / 8) to obtain 54 mg of solid 4-methyl-5H-indeno[1,2-b]pyridine with a yield of 30%. It can also be dried (MgSO ...

Embodiment 3

[0027] Example 3: Synthesis of 4-methyl-5H-indeno[1,2-b]pyridin-5-one (Onychine)

[0028] 4-Methyl-5H-indeno[1,2b]pyridine (1.0mmol) and 10mL acetone were contained in a single-necked bottle, and KMnO was added under stirring at room temperature 4 (5.0 mmol). After continuing to stir the reaction at room temperature for 6 hours, 0.1 mL of ethanol was added to quench the reaction. After filtration, the mother liquor was concentrated and a solid appeared. The concentrated solution was recrystallized from ethanol to obtain 0.15 g of yellow solid 4-methyl-5H-indeno[1,2-b]pyridin-5-one with a yield of 80%. 1 H NMR (300MHz, CDCl 3 ): δ 8.42 (1H, d, J = 5.1Hz), 7.83 (1H, d, J = 7.5Hz), 7.69 (1H, d, J = 7.5Hz), 7.60 (1H, t, J = 7.5Hz) , 7.42 (1H, t, J = 7.5Hz), 6.97 (1H, d, J = 8.1Hz), 6.97 (1H, d, J = 8.1Hz), 2.64 (3H, s). The same result was obtained with chromium trioxide.

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Abstract

The invention discloses a method for synthesizing alkaloid Onychine, comprising the following steps: (1) under the action of a metal salt catalyst, indenone and 2-butine-1-amine generate 4-methyl-5H-indeno(1, 2-b) naphthyridine by a series of reactions; wherein, the dosage of the 2-butine-1-amine is 1.0 to 3.0 equivalent of the indenone; a catalyst is Au salt or platinum salt; the dosage of the catalyst is 0.01 to 1.0 equivalent of the indenone; (2) C-H at the benzyl position of the 4-methyl-5H-indeno(1, 2-b) naphthyridine is selectively oxidized to a keto carbonyl group, so as to generate the Onychine; the 4-methyl-5H-indeno(1, 2-b) naphthyridine is selectively oxidized by a selective C-H bond to generate the Onychine; and an oxidizer is a metal oxidant of potassium permanganate, chromium trioxide or the combination between metal cupric salt, malysite, dioxygen and peroxide.

Description

1. Technical field [0001] The invention relates to a methodology for forming a novel carbon-carbon bond and carbon-nitrogen bond catalyzed by a transition metal and a total synthesis method for 4-azafluorenone natural alkaloid Onychine. 2. Background technology [0002] Onychine is a natural alkaloid with the structure of 5H-indeno[1,2-b]pyridin-5-one, which mainly exists in the species of Annonaceae. Some 5H-indeno[1,2-b]pyridin-5-one alkaloids substituted with hydroxyl and methoxy groups on ring A have been discovered one after another, and have been tested to have obvious anti-candida and fungal activities. (De Almeida, M.E.I.; Braz, F.R.; von Bulow, M.V.; Gottleib, O.R.; Maia, J.G.S. Phytochemistry 1976, 15, 1186. Arango, G.J.; Cortes, D.; Cassels, B.K.; Cave, A.; Merienne, C. . Phytochemistry 1987, 26, 2093.) [0003] Structural formula one [0004] [0005] Chemists' initial interest in the synthesis of this type of alkaloids with a 6-5-6 tricyclic structure stem...

Claims

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Application Information

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IPC IPC(8): C07D221/16
Inventor 王少仲李舒衡
Owner NANJING UNIV