Preparation method of natural product alkaloid aaptamine

A technology of natural products and alkaloids, applied in the direction of organic chemistry, can solve the problems of many by-products, harsh reaction conditions, and low yields

Active Publication Date: 2015-10-07
HEBEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to provide a method for synthesizing natural products using 6,7-dimethoxy-1-methylisoquinoline as a raw material for the shortcomings of many by-products and harsh reaction conditions resulting in low yields in the prior art. The Alkaloid Aaptamine Method

Method used

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  • Preparation method of natural product alkaloid aaptamine
  • Preparation method of natural product alkaloid aaptamine
  • Preparation method of natural product alkaloid aaptamine

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preparation example Construction

[0037] (5) Preparation of Aaptamine: the alkaloid Aaptamine was prepared from compound 5 through iron powder reduction and ring closure.

[0038] The reaction formula is as follows:

[0039]

Embodiment 1

[0040] Embodiment 1: the preparation of Aaptamine

[0041] (1) Preparation of 6,7-dimethoxyisoquinoline-1-carbaldehyde

[0042] Its reaction formula is:

[0043]

[0044] Under nitrogen protection, at 97~100°C, 6,7-dimethoxy-1-methylisoquinoline (2.03g, 10mmol) was dissolved in 1,4-dioxane (1,4-dioxane The amount is enough to dissolve 6,7-dimethoxy-1-methylisoquinoline (actually 60mL) solution was added dropwise to the 1,4-dioxygen dioxide (1.33g, 12mmol) Hexacyclic (the amount of 1,4-dioxane is enough to contain selenium dioxide, actually 30mL) solution, then reflux for 2 hours, TLC detection, after the reaction is complete, filter, the filtrate is precipitated, and the solid residue Dissolve in dichloromethane, wash the organic phase twice with water, dry, remove the solvent, and obtain a pink solid by column chromatography. Yield 80%, melting point 169–171°C. 1 HNMR (CDCl 3 ,400MHz): δ4.06(s,3H),4.10(s,3H),7.14(s,3H),7.74(d,J=5.6Hz,1H),8.63(d,J=5.2Hz,1H) ,8.75(s,1H...

Embodiment 2

[0061] Embodiment 2: the preparation of Aaptamine

[0062] Other each steps operation is the same as embodiment 1, difference is the preparation of step (1) 6,7-dimethoxyisoquinoline-1-carbaldehyde:

[0063] Under nitrogen protection, at 95-98°C, a solution of 6,7-dimethoxy-1-methylisoquinoline (2.03g, 10mmol) in 1,4-dioxane (60mL) was added dropwise to Selenium dioxide (1.33g, 12mmol) in 1,4-dioxane (30mL) solution, refluxed for 2 hours, TLC detection, after the reaction was complete, filtered, the filtrate was precipitated, and the solid residue was dissolved with dichloromethane , the organic phase was washed twice with water, dried and precipitated, and a pink solid was obtained by column chromatography with a yield of 78%.

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Abstract

The invention relates to a method for preparing a natural product alkaloid Aaptamine. The method comprises the steps of (1) oxidizing 6,7-dimethoxy-1-methylisoquinoli by selenium dioxide to prepare 6,7-dimethyl isoquinoline-1-methanal; (2) in an alkaline condition, carrying out addition reaction on the 6,7-dimethyl isoquinoline-1-methanal with nitromethane to prepare 1-(6,7-dimethoxy isoquinoline-1-yl)-2-nitroethanol; (3) under dimethylaminopyridine (DMAP) catalysis, carrying out acylation on 1-(6,7-dimethoxy isoquinoline-1-yl)-2-nitroethanol and acetic anhydride, then eliminating to prepare (E)-6,7-dimethoxy-1-(2-nitroolefin) isoquinoline; (4) in the condition of concentrated nitric acid-concentrated sulfuric acid, carrying out nitration reaction on (E)-6,7-dimethoxy-1-(2-nitroolefin) isoquinoline to prepare (E)-6,7-dimethoxy-8-nitro-1-(2-nitroolefin) isoquinoline); and (5) reducing the (E)-6,7-dimethoxy-8-nitro-1-(2-nitroolefin) isoquinoline) by iron powder to generate ring-closing reaction to prepare the alkaloid Aaptamine.

Description

technical field [0001] The invention relates to a preparation method of natural product alkaloid Aaptamine, which belongs to the technical field of resources, medicine and chemical industry. Background technique [0002] Aaptamine and its natural congeners are collectively referred to as Aaptamines, which are marine alkaloids with a benzo[de][1,6]naphthyridine skeleton. Since 1981, Nakamura and others have extracted Aaptamine from marine sponge organisms in Okinawa Prefecture, Japan for the first time (Nakamura, H., Kobayashi, J., Ohizumi, Y., Hirata, Y. Tetrahedron Lett., 1982,23:5555– 5558.), Aaptamines alkaloids of other structures such as: isoaapatamine, 9-demethyl-aaptamine, etc. have been reported successively. At present, there are more than 20 known structures of Aaptamines extracted from vulgaris sponges. This kind of marine natural product alkaloids with benzo[de][1,6]naphthyridine skeleton has the advantages of simple core structure, easy modification, good biol...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): C07D471/06
CPCC07D471/06
Inventor卢爱党陈建新李银辉韩健苏敏王瑾瑾
OwnerHEBEI UNIV OF TECH