Synthesis of berberine bromide analogs containing tertiary amides of acetic acid in the 9-O-position

Abstract

547.978.1+547.833.8 V. G. Vasilcev, and N. F. Salakhutdinov 9-O-Acetamide analogs of berberine bromide were prepared in 20-87% yields via reaction of the isoquinoline alkaloid berberrubine with tertiary amides of bromoacetic acid. Aminolysis did not occur during reaction of methyl-2-(9-demethoxyberberine bromide-9-yl)hydroxyacetate with secondary amines. The corresponding acid or its ethyl ester was isolated.The leading cause of death (greater than 50% of all lethalities) in the majority of economically developed countries remains as before cardiovascular diseases (CVD) of atherosclerotic origin and their complications (acute myocardial infarct, sudden cardiac death). Hyperlipidemia and, in particular, hypercholesterolemia is the principal risk factor of atherosclerotic CVD. Drugs used in medical practice and developed to lower cholesterol can be divided into two classes that differ in principle according to their mechanism of action. The first class includes drugs that inhibit the synthesis of endogenous cholesterol. Such chemical compounds (e.g., statins) interrupt the synthetic pathway of cholesterol in vivo by blocking (mostly by a competing mechanism) the activity of the corresponding enzyme. The second class comprises compounds that regulate by one method or another the amounts of cholesterol already synthesized by the body or obtained in food and enable its amount to be maintained within acceptable limits.

Natural Aromatic Compounds as Scaffolds to Develop Selective G-Quadruplex Ligands: From Previously Reported Berberine Derivatives to New Palmatine Analogues

“…Reaction 2: Compound ( 1 ) present in CH 2 Cl 2 was treated with the ethyl ester of bromoacetic acid in a ratio of 1:2 ( v / v ), stirred on a magnetic stirrer, and refluxed for 12 h, as suggested in the literature [ 36 ]. The resulting yellow precipitate was filtered off, refluxed with EtOH for 30 min, cooled, filtered off again, and dried in a vacuum to give compound ( 2 ) with a yield of 55%.…”

“…Reaction 3: Compound ( 2 ) was dissolved in a solution of CH 3 OH/H 2 O (1:1 ( v / v )). Then, NaOH in a ratio of 1:2 ( w / w ) was added under reflux for 12 h on a water bath, and the solution was cooled [ 36 ]. At this point, HCl was added until a pH value of 1 was obtained.…”

Synthesis, Characterization, and Biological Evaluations of 1,3,5-Triazine Derivatives of Metformin Cyclization with Berberine and Magnolol in the Presence of Sodium Methylate

“…Compared with compounds 1 and 2 , the ring closure reaction of compound 3 underwent an analogous process. According to a review of Cao’s and Nechepurenko‘s studies [ 21 , 22 ], the initial step was a pintsch reaction in berberine hydrochloride ( 8 ), which led to the product berberrubine ( 9 ). Then, the hydroxyl radical of berberrubine ( 9 ) engaged in the nucleophile substitution reaction with the bromine group of methyl bromoacetate ( 6 ) and gave the intermediate product ( 10 ).…”

Selective Interactions with Various G-Quadruplex DNA Forming Sequences by Berberine and Palmatine Analogues

“…The solution was heated to 180°C, with a voltage of 400W, for 5-10 minutes. The reaction gave a red precipitate (compound (2)) that was washed and filtered with ether under vacuum with a final yield of 95%.Compound (6) present in CH2Cl2, was treated with the ethyl ester of bromoacetic acid in ratio 1:2 (v/v), stirred on a magnetic stirrer, and refluxed for 12 h as suggested in literature[39].The resulting yellow precipitate was filtered off, refluxed with EtOH for 30 min, cooled, filtered off again and dried in vacuum to give the final compound with a yield of 55%.Compound(7) was dissolved in a solution of CH3OH/H2O (1:1 (v/v)). Then, NaOH in ratio 1:2 (w/w), was added under reflux for 12 h on a water bath and the solution was cooled[39].At this point, HCl was added until a pH value of 1.…”

“…The reaction gave a red precipitate (compound (2)) that was washed and filtered with ether under vacuum with a final yield of 95%.Compound (6) present in CH2Cl2, was treated with the ethyl ester of bromoacetic acid in ratio 1:2 (v/v), stirred on a magnetic stirrer, and refluxed for 12 h as suggested in literature[39].The resulting yellow precipitate was filtered off, refluxed with EtOH for 30 min, cooled, filtered off again and dried in vacuum to give the final compound with a yield of 55%.Compound(7) was dissolved in a solution of CH3OH/H2O (1:1 (v/v)). Then, NaOH in ratio 1:2 (w/w), was added under reflux for 12 h on a water bath and the solution was cooled[39].At this point, HCl was added until a pH value of 1. The resulting yellow precipitate was filtered off and dried in vacuo to give the final compound with a yield of 45 %.To have compounds (9a-9g), the intermediate compound(8) for the weight of 200 mg was mixed with deprotected peptidyl side chains using DIC/HOBT (475 mg/500 mg) in DMF (4 mL) with shaking for 12 h. After coupling with compound (8), the resin was treated with the cleavage reagent (95% TFA, 5% dd H2O (v/v)) for 2 h, washed with dry ether (30 mL), and then evaporated under vacuum.…”