1484-85-1

Basic information

• Product Name: HOMOPIPERONYLAMINE
• Synonyms: 3,4-methylenedioxy-phenethylamin;methylenedioxyphenethylamine;methylenedioxyphenylethylamine;benzo-1,3-dioxole-5-ethylamine;Homopiperonylamine=1,3-Benzodioxole-5-ethanamine;1,3-BENZODIOXOLE-5-ETHYLAMINE;2-(3,4-Methylenedioxyphenyl)Et;2-(3,4-METHYLENEDIOXYPHENYL)ETHYLAMINE(HOMOPIPERONYLAMINE)
• CAS NO: 1484-85-1
• Molecular Formula: C₉H₁₁NO₂
• Molecular Weight: 165.19
• EINECS: 216-060-8
• Product Categories: Pharmaceutical Intermediates;Intermediates;Amines;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 1484-85-1.mol
• Article Data: 46

Chemical Properties

• Melting Point: 114 °C
• Boiling Point: 146-148°C/10 mm
• Flash Point: 129.8 ºC
• Appearance: Colorless to pale yellow/Liquid
• Density: 1.2250
• Vapor Pressure: 0.000618mmHg at 25°C
• Refractive Index: 1.5620 (estimate)
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform, Methanol
• PKA: 9.90±0.10(Predicted)
• Sensitive: Air Sensitive
• CAS DataBase Reference: HOMOPIPERONYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: HOMOPIPERONYLAMINE(1484-85-1)
• EPA Substance Registry System: HOMOPIPERONYLAMINE(1484-85-1)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39-24/25
• RTECS: SH9670000
• Hazardous Substances Data: 1484-85-1(Hazardous Substances Data)

Usage

Chemical Properties

Colourless Liquid

Uses

Different sources of media describe the Uses of 1484-85-1 differently. You can refer to the following data:
1. An intermediate in the synthesis of pharmaceutical actives, intermediates and other fine chemicals
2. A metabolite of Dopamine analogs
3. 3,4-(Methylenedioxyphenyl)ethylamine is a metabolite of Dopamine analogs.

InChI:InChI=1/C10H13NO3/c1-12-8-4-7(2-3-11)5-9-10(8)14-6-13-9/h4-5H,2-3,6,11H2,1H3

Synthetic route

5-(2-nitrovinyl)benzo[1,3]dioxole (1485-00-3) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 20 - 70℃; for 4h;	100%
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 4h;	95%
With diisobutylaluminium hydride In 1,4-dioxane at 60℃; for 3h;	82%

benzyl N-[2-(benzo[1,3]dioxol-5-yl)ethyl]carbamate (550358-40-2) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal In tetrahydrofuran; methanol at 20℃; under 760 Torr; for 3h;	100%

C9H9NO2 → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogen In ethanol at 70℃; under 112511 Torr; for 6h; Green chemistry;	95.6%

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at 0 - 70℃; for 12h; Inert atmosphere;	95%
With lithium aluminium tetrahydride In tetrahydrofuran Reflux;	87%
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; Reflux;	84%

3,4-methylenedioxyphenylacetonitrile (4439-02-5) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With lithium aluminium tetrahydride; aluminium trichloride In diethyl ether for 2h;	92%
With diisobutylaluminium hydride In tetrahydrofuran at 60℃; for 3h; Product distribution; other solvent, temp., time, reagent;	80%
With diisobutylaluminium hydride In tetrahydrofuran at 60℃; for 3h;	80%

3-(benzo[d][1,3]dioxol-5-yl)propanamide (20799-84-2) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With chlorine; sodium hydroxide In water at -5 - 40℃; for 4h; Reagent/catalyst; Temperature;	91%
With chlorine; sodium hydroxide at 30 - 75℃; for 2h; Green chemistry;	90%
With sodium hydroxide; bromine In water at 70 - 80℃; for 0.25h;	71%
With sodium hypochlorite at 70 - 80℃;

5-(2-nitroethyl)benzo[1,3]dioxole (21473-47-2) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With lithium aluminium tetrahydride	75%
With hydrogenchloride; iron In methanol; water for 0.5h; Heating;	71%
With hydrogenchloride; zinc
With hydrogenchloride; zinc In ethanol; water for 3h;

5-(2-nitro-1(Z)-ethenyl)benzo[d][1,3]dioxol → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogenchloride; iron In methanol; water for 0.5h; Heating;	70%

benzo[1,3]dioxol-5-yl-acetaldehyde-oxime (153361-93-4) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With sodium amalgam; acetic acid
With ethanol; calcium
With ethanol; sodium

α-acetoxy-2-(3,4-methylenedioxyphenyl)acetonitrile (119798-32-2) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With methanol; palladium; acetic acid Hydrogenation.Zusatz von wenig Salzsaeure;
With sulfuric acid; palladium; acetic acid Hydrogenation;

piperonal (120-57-0) + nitromethane (75-52-5) → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogenchloride; methylamine hydrochloride; sodium acetate; mercury; zinc 1.) room temperature, 2.) MeOH; Yield given. Multistep reaction;

ω-nitro-3.4-methylenedioxy-styrene → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With ethanol Electrolysis;
With water Electrolysis;

ethanol (64-17-5) + benzo[1,3]dioxol-5-yl-acetaldehyde-oxime (153361-93-4) + calcium → 3,4-methylenedioxyphenylethylamine (1484-85-1)

homopiperonylic acid nitrile → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With pentan-1-ol; sodium
With ethanol; sodium

ethanol (64-17-5) + 5-(2-nitrovinyl)benzo[1,3]dioxole (1485-00-3) + lead-cathode → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
bei der elektrolytischen Reduktion;

benzo[1,3]dioxol-5-yl-acetaldehyde-oxime (153361-93-4) + acetic acid (64-19-7) + lead cathode → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
bei der elektrolytischen Reduktion;

benzo[1,3]dioxol-5-yl-acetaldehyde-oxime (153361-93-4) + lead cathode + alcoholic-aqueous sulfuric acid → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
bei der elektrolytischen Reduktion;

5-(2-nitrovinyl)benzo[1,3]dioxole (1485-00-3) + aqueous suspension + lead-cathode → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
bei der elektrolytischen Reduktion;

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) + diethyl ether (60-29-7) + lithium alanate → 3,4-methylenedioxyphenylethylamine (1484-85-1)

1,4-dioxane (123-91-1) + 5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) + diethyl ether (60-29-7) + lithium alanate → 3,4-methylenedioxyphenylethylamine (1484-85-1)

diethyl ether (60-29-7) + (7-bromo-benzo[1,3]dioxol-5-yl)-acetonitrile + lithium alanate → 3,4-methylenedioxyphenylethylamine (1484-85-1)

diethyl ether (60-29-7) + (E)-3-bromo-4,5-methylenedioxy-β-nitro-styrene (13326-78-8) + lithium alanate → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
5 Mol Lithiumalanat; 10-stdg. Erwaermen;

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) + diethyl ether (60-29-7) + benzene (71-43-2) + lithium alanate → 3,4-methylenedioxyphenylethylamine (1484-85-1)

N-acetyl-homopiperonylamine → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogenchloride im Rohr;

O-acetyl-3.4-methylenedioxy-thiomandelic acidamide → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With hydrogenchloride; zinc at 25 - 30℃; bei der elektrolytischen Reduktion;

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) + sulfuric acid (7664-93-9) + acetic acid (64-19-7) + palladium → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
Hydrogenation;

piperonyl cyanide → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
With ammonia; nickel at 100 - 125℃; under 26600 - 53200 Torr; Hydrogenation;

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) + sulfuric acid (7664-93-9) + ethyl acetate (141-78-6) + platinum → 3,4-methylenedioxyphenylethylamine (1484-85-1)

Conditions	Yield
Hydrogenation;

benzo[1,3]dioxol-5-yl-acetaldehyde-oxime (153361-93-4) + acetic acid (64-19-7) + sodium amalgam → 3,4-methylenedioxyphenylethylamine (1484-85-1)

3,4-methylenedioxyphenylethylamine (1484-85-1) + acetic anhydride (108-24-7) → N-[2-(3,4-methylenedioxyphenyl)ethyl]acetamide (58026-25-8)

Conditions	Yield
In toluene at 20℃;	100%

succinic acid anhydride (108-30-5) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → 1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)pyrrolidine-2,5-dione (191015-17-5)

Conditions	Yield
With dmap; acetic acid for 24h; Heating;	100%

3,4-methylenedioxyphenylethylamine (1484-85-1) + 4-Nitrobenzenesulfonyl chloride (98-74-8) → N-p-nitrobenzenesulfonyl-3,4-methylenedioxyphenethylamine

Conditions	Yield
Stage #1: 3,4-methylenedioxyphenylethylamine With triethylamine In dichloromethane Cooling with ice; Stage #2: 4-Nitrobenzenesulfonyl chloride In dichloromethane at 20℃; for 4.5h;	100%
With triethylamine In dichloromethane at 20℃; for 4.5h; Alkaline conditions; Cooling with ice;	100%

ethyl 2-(2-oxocyclohexyl)acetate (24731-17-7) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → C17H19NO3

Conditions	Yield
Stage #1: ethyl 2-(2-oxocyclohexyl)acetate; 3,4-methylenedioxyphenylethylamine With In(OSO2CF3)3; trimethylaluminum In toluene; acetonitrile at 25℃; for 17h; Stage #2: With trifluorormethanesulfonic acid In toluene; acetonitrile at 25℃; for 5h; Further stages.;	99%

1-bromo-2,2-dimethoxyethane (7252-83-7) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → C13H19NO4 (1160948-79-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;	99%

C22H22N2O3 + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-piperonyl-3-methylbenzamide

Conditions	Yield
With [(1,2,3-N)-3-phenyl-2-propenyl][1,3-bis(2,6-diisopropylbenzene)-4,5-dihydroimidazol-2-yl]palladium chloride; potassium carbonate In tetrahydrofuran at 110℃; for 24h; Schlenk technique; Inert atmosphere;	99%

2,4-difluorobenzene-1-sulfonyl chloride (13918-92-8) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2,4-difluorobenzenesulfonyl)-3,4-methylenedioxyphenylethylamine

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 4h; Cooling with ice; Alkaline conditions;	99%

4,5,6,7-tetrahydrocyclopentapyran-2(3H)-one (5587-71-3) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-<2-<3,4-(methylenedioxy)phenyl>ethyl>-3-(2-oxocyclopentyl)propionamide (114942-64-2)

Conditions	Yield
In benzene for 1h; Heating;	98%

trifluoromethylsulfonic anhydride (358-23-6) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-trifluoromethylsulfonyl-3,4-methylenedioxyphenethylamine (1180007-79-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In chloroform at 20℃; for 4h; Alkaline conditions; Cooling with ice;	98%
With triethylamine In dichloromethane at -78℃; for 1h; Inert atmosphere;

6-iodo-2,3-dimethoxybenzoic acid (56221-41-1) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → C18H18INO5

Conditions	Yield
With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine	98%

di-tert-butyl dicarbonate (24424-99-5) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → (2-benzo[1,3]dioxol-5-yl-ethyl) carbaminic acid tert-butyl ester (191847-31-1)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h;	97%
Stage #1: 3,4-methylenedioxyphenylethylamine With 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine In ethanol Cooling with ice; Stage #2: di-tert-butyl dicarbonate In dichloromethane at 20℃; for 5.5h;	94%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine In ethanol at 20℃; for 5.5h; Cooling with ice; Alkaline conditions;	94%

piperonal (120-57-0) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → (2-Benzo[1,3]dioxol-5-yl-ethyl)-[1-benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-amine (855391-64-9)

Conditions	Yield
Stage #1: piperonal; 3,4-methylenedioxyphenylethylamine at 160℃; for 1h; Stage #2: With methanol; sodium tetrahydroborate at 20℃; for 1h; Reflux;	97%
With sodium sulfate In dichloromethane for 2h;
at 160℃; for 1h;

3,4-methylenedioxyphenylethylamine (1484-85-1) + naphthalene-2-carboxylate (93-09-4) → N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-naphthamide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h;	97%

C10H8F3NO3 (1273678-30-0) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-((2-benzo[1,3]dioxol-5-ylethylcarbamoyl)methyl)phenyl)-2,2,2-trifluoroacetamide (1390646-87-3)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	97%

indole-3-acetic acid (87-51-4) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-benzo[1,3]dioxol-5-ylethyl)-2-(1H-indol-3-yl)acetamide

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	97%

3,4-methylenedioxyphenylethylamine (1484-85-1) + benzaldehyde (100-52-7) → 5-phenyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline (55507-12-5)

Conditions	Yield
Reflux; Acidic conditions;	97%

3,4-methylenedioxyphenylethylamine (1484-85-1) + 2-Nitrobenzenesulfonyl chloride (1694-92-4) → N-o-nitrobenzenesulfonyl-3,4-methylenedioxyphenethylamine

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 4h; Cooling with ice; Alkaline conditions;	97%

formaldehyd (50-00-0) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → 5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline (94143-83-6)

Conditions	Yield
With formic acid for 12h; Pictet-Spengler cyclization; Heating;	96%
In formic acid at 50℃; for 30h;	76%
Reflux; Acidic conditions;	73%

2-(2-nitrophenyl)acetic acid (3740-52-1) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(2-nitrophenyl)acetamide (73903-39-6)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	96%

4-hydroxyphenylacetate (156-38-7) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-benzo[1,3]dioxol-5-ylethyl)-2-(4-hydroxyphenyl)acetamide (1390646-85-1)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	96%

3,4-methylenedioxyphenylethylamine (1484-85-1) + oxalic acid diethyl ester (95-92-1) → N-(2-benzo[1,3]dioxol-5-yl-ethyl)-oxalamic acid ethyl ester (91958-62-2)

Conditions	Yield
In toluene for 10h; Heating;	95%
With benzene

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-<2-(3,4-methylenedioxyphenyl)-ethyl>methoxycarbonylacetamide (79641-43-3)

Conditions	Yield
With potassium carbonate In diethyl ether; chloroform at 0℃;	95%
at 0℃;	95%

Thiophene-2-acetic acid (1918-77-0) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(thiophen-2-yl)acetamide (92851-34-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 6h;	95%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	74%

naphth-1-yl acetic acid (86-87-3) + 3,4-methylenedioxyphenylethylamine (1484-85-1) → N-(2-benzo[1,3]dioxol-5-ylethyl)-2-naphthalen-1-ylacetamide

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃;	95%

3,4-methylenedioxyphenylethylamine (1484-85-1) + 4-nitrobenzaldehdye (555-16-8) → N-(4-nitrobenzylidene)-2-(3,4-methylenedioxyphenyl)ethanamine

Conditions	Yield
In neat (no solvent) at 20℃; Milling;	95%

3,4-methylenedioxyphenylethylamine (1484-85-1) + 1-ethoxycarbonyl-3-phenylamino-maleimide (69581-53-9) → [(E)-3-(2-Benzo[1,3]dioxol-5-yl-ethylcarbamoyl)-3-phenylamino-acryloyl]-carbamic acid ethyl ester

Conditions	Yield
In acetone for 24h; Ambient temperature;	94.1%

Upstream product

• 153361-93-4 benzo[1,3]dioxol-5-yl-acetaldehyde-oxime 
• 120-57-0 piperonal 
• 75-52-5 nitromethane 
• 1485-00-3 5-(2-nitrovinyl)benzo[1,3]dioxole 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 775-01-9 3,4-dihydroxymandelic acid 
• 274-09-9 Methylenedioxybenzene 
• 689-98-5 chloroethylamine 
• 55418-52-5 cassione 
• 5703-61-7 3-(3',4'-methylendioxyphenyl)propanenitrile 
• 74402-06-5 2-benzo[1,3]dioxol-5-ylmethylmalonic acid dimethyl ester 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 22180-30-9 Diethyl α-piperonylmalonate 
• 120-80-9 benzene-1,2-diol 

Downstream Products

• 855167-11-2 2-phenyl-quinoline-4-carboxylic acid-(2-benzo[1,3]dioxol-5-yl-ethylamide) 
• 159152-07-5 α-methyl-N-(3,4-methylenedioxy-β-phenethyl) propionamide 
• 171516-52-2 N-(hydroxybenzyl)-3,4-dimethylenedioxyphenethylamine 
• 171516-53-3 N-(2-methoxybenzyl)-3,4-dimethylenedioxyphenethylamine 
• 51-67-2 tyrosamine 
• 113135-94-7 (2,3-dimethoxy-6-nitro-phenyl)-acetic acid homopiperonylamide 
• 99004-00-9 bis[3,4-(methylenedioxy)phenethyl]amine 
• 550358-40-2 benzyl N-[2-(benzo[1,3]dioxol-5-yl)ethyl]carbamate 
• 550358-41-3 N-[2-(benzo[1,3]dioxol-5-yl)ethyl]-2-(2,2-dichlorovinyl)-5,6-dimethoxybenzamide 
• 936482-24-5 (4R,5R)-ethyl 1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-5-nitro-2-oxo-4-(2,4,5-trifluorophenyl)-piperidine-3-carboxylate 
• 87201-30-7 N-<-2-(3,4-methylenedioxyphenyl)ethyl>-2'-bromophenylacetamide 
• 112448-26-7 5-(4-Benzyloxy-3-methoxy-benzyl)-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline 
• 112448-30-3 7-Benzyloxy-6-methoxy-2-methyl-3-(6-vinyl-benzo[1,3]dioxol-5-yl)-2H-isoquinolin-1-one 
• 112448-27-8 10-Benzyloxy-11-methoxy-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline 

Relevant articles and documents

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Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure–activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 μM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.

A synthetic preparation method for small carbags hydrochloric acid

The present invention belongs to the field of organic chemistry, relates to a method of synthesizing berberine hydrochloride, comprising: S1: with 5-halo-o-quinoastearaldehyde and piperine ethylamine to obtain N- [2-(3,4-dimethoxyphenyl-5-yl) ethyl] -1- (5-halo-2,3-dimethoxybenzyl) methylimide; S2: to obtain 2- (3,4-diimoxyphenyl) -N- (5-bromo-2,3-dimethoxybenzyl) ethylamine; S3: to obtain 2-(3,4-dimethoxyphenyl) -N- (5-bromo-2 S4: to obtain 12-halogenated berberine derivative; S5: to obtain berberine. The present invention is free from the application of the by-product o-vanillin synthesis of o-resveratal raw material constraints, synthesis of 5- substitute o-resveratal and piperine ethylamine, and the use of the two preparation of berberine hydrochloride, with raw materials readily available, mild reaction conditions, easy to operate, high chemical yield, low cost and other advantages.

Method for total synthesis of berberine with guaiacol as raw material

The invention discloses a method for total synthesis of berberine with guaiacol as a raw material. According to a drug synthesis method, guaiacol serves as the raw material, 2-hydroxy-3-methoxybenzaldehyde is obtained through a selective formylation reaction, 2,3-dimethoxybenzaldehyde is obtained through a methylation reaction, pentamethyleneamine is obtained through a methylenenation reaction with catechol as a raw material, and homopiperony lamine is obtained through a one-step catalytic addition reaction; 2,3-dimethoxybenzaldehyde and homopiperony lamine are subjected to a one-pot condensation hydrogenation reaction under the condition of a nickel-based catalyst, hydrochloric acid is added to a reaction product, a crystal substance is cooled, after the reaction product is refined, hydrochloric acid is added, and cooling crystallization and filtration washing are conducted to obtain the product berberine. According to the method, the technology is simplified, and the use of toxic cyanide is avoided; 2,3-dimethoxybenzaldehyde and homopiperony lamine are subjected to a one-pot condensation hydrogenation and salifying technology, the time is saved, the energy is saved, and the costis lowered; in the technological process, solvents are recycled.