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A kind of tropane type alkaloid and its synthetic method

A synthesis method and compound technology, applied in the fields of drug combination, organic chemistry, cardiovascular system diseases, etc.

Active Publication Date: 2020-04-21
SOUTH CENTRAL UNIVERSITY FOR NATIONALITIES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, isolated rat thoracic aorta is a main method for studying vascular endothelium, smooth muscle cells and vasodilation. It has a regulatory effect and is likely to have an inhibitory effect on the occurrence and development of hypertension

Method used

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  • A kind of tropane type alkaloid and its synthetic method
  • A kind of tropane type alkaloid and its synthetic method
  • A kind of tropane type alkaloid and its synthetic method

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0023] (1) Preparation of compound 3:

[0024]

[0025] Operational references: Gong Chen; Gang He. Angew. Chem. Int. Ed., 2011, 50, 5192–5196.

[0026] (2) Preparation of compound 5:

[0027]

[0028] The procedure was as follows: 1-Aminocycloheptanoic acid (560 mg, 3.56 mmol) and 4 mL of methanol were added to a 15 mL round bottom flask and stirred in an ice bath. Thionyl chloride (0.8 mL, 11 mmol) was added dropwise thereto, gradually returned to room temperature, and reacted overnight. After the reaction, evaporate to dryness under reduced pressure, add a small amount of petroleum ether and filter, and wash the solid several times with a small amount of petroleum ether to obtain a white solid, namely 1-aminocycloheptyl ester hydrochloride. The resulting 1-aminocycloheptyl ester hydrochloride, picolinic acid (529 mg, 4.3 mmol), EDCI (1.04 mg, 5.4 mmol), DMAP (50 mg, 0.4 mmol) and dichloromethane (5 mL) were added to a 10 mL round bottom flask , the reaction was sti...

Embodiment 1

[0032] The preparation of embodiment 1 compound 4:

[0033]

[0034] The operation is as follows: at room temperature, 2-pyridinecarboxylic acid protected cycloheptylamine 3 (ie compound 3) (21.8mg, 0.1mmol), PdCl 2 (1.8mg, 0.01mmol), Ag 2 CO 3 (55.2mg, 0.2mmol), 4-Iodonitrobenzene (49.8mg, 0.2mmol), 2,6-Dimethoxybenzoic acid (36.4mg, 0.2mmol), Na 3 PO 4 (41.0mg, 0.25mmol) and TCE (1mL) were added into a 10mL microwave reaction tube with a power of 20W and reacted at 140°C for 2 hours. After the reaction was completed, it was naturally cooled to room temperature, filtered through celite, and spin-dried. Using petroleum ether: ethyl acetate = 2:1 as a developing solvent, 19.1 mg of the target compound 4 was obtained through preparative plate separation, with a yield of 88%. 1 H NMR (400MHz, CDCl 3 )δ8.57(d,J=4.6Hz,1H),7.85–7.66(m,2H),7.37–7.27(m,1H),4.84(s,1H),4.57(s,1H),2.06–1.72 (m,7H), 1.66–1.52(m,2H),1.51–1.41(m,1H); 13 C NMR (100MHz, CDCl 3 )δ164.1, 154.6, 148....

Embodiment 2

[0035] The preparation of embodiment 2 compound 6:

[0036]

[0037] The operation is as follows: at room temperature, the 2-pyridinecarboxylic acid protected cycloheptylamine derivative 5 (ie compound 5) (27.6mg, 0.1mmol), PdCl 2 (1.8mg, 0.01mmol), Ag 2 CO 3 (55.2mg, 0.2mmol), 2-Iodobenzonitrile (45.8mg, 0.2mmol), 2,6-Dimethoxybenzoic acid (36.4mg, 0.2mmol), Na 3 PO 4 (41.0mg, 0.25mmol) and TCE (1mL) were added into a 10mL microwave reaction tube with a power of 20W and reacted at 140°C for 2 hours. After the reaction was completed, it was naturally cooled to room temperature, filtered through celite, and spin-dried. Using petroleum ether: ethyl acetate = 2:1 as the developing solvent, 12.0 mg of the target compound 6 was obtained by separation through a preparative plate, with a yield of 44%. 1 H NMR (400MHz, CDCl 3 )δ8.57(d,J=4.1Hz,1H),7.92–7.68(m,2H),7.35(t,J=5.1Hz,1H),5.20–5.05(m,1H),3.73(s,3H ),2.43–2.22 (m,3H),2.05–1.92(m,2H),1.85–1.68(m,3H),1.53–1.34(m,2H); ...

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Abstract

The invention relates to the technical field of chemical synthesis, and a tropane alkaloid and a synthesis method thereof are particularly disclosed. The structure formula (I) of the target product scopolamine alkaloid is described in the description, the compound of formula (I) is a compound containing a five-membered aza-bridged ring skeleton in which that nitrogen atom is protected by 2-pyridinecarboxylic acid; R1 is hydrogen or methoxycarbonyl; R2 is hydrogen or substituted phenyl, and the tropane alkaloid is racemic. Compounds of formula (I) have a significant relaxing effect on KCl-precontracted rat thoracic aorta, suggesting that compounds of formula (I) have a modulatory effect on vascular endothelial cells or smooth muscle cells, and may inhibit the occurrence and development of hypertension.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and specifically relates to a class of tropane-type alkaloids represented by formula (I) containing a five-membered aza bridge ring skeleton and a synthesis method thereof. Background technique [0002] Tropane-type alkaloids, whose structure contains Tropane (Tropane), that is, a five-membered aza bridge ring. This type of compound has significant biological activity, such as Atropine (Atropine), Scopolamine (Scopolamine), Anisodamine (Anisodamine) etc., are M choline receptor antagonists. It has the effects of inhibiting glandular secretion, dilating pupils, accelerating heart rate, relaxing bronchi and gastrointestinal smooth muscle. It is clinically used to treat peptic ulcer, visceral colic caused by smooth muscle spasm, epilepsy, seasickness, etc. [0003] [0004] Tropine-type alkaloids are esters formed from tropine and different organic acids, and tropine can be obtained by reducin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D451/02A61P9/12
CPCC07D451/02
Inventor 吴滨赵杰
Owner SOUTH CENTRAL UNIVERSITY FOR NATIONALITIES
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