517-66-8

Usage

Uses

Used in Pharmaceutical Industry:
Dicentrin is used as an antinociceptive agent for alleviating pain in a mouse model, potentially through a TRPA1-dependent mechanism. Its effectiveness in pain management makes it a valuable compound for the development of new pain relief medications.
Used in Anticancer Applications:
Dicentrin is utilized as an antitumor agent, specifically through the inhibition of topoisomerase II. This action contributes to its potential use in the development of cancer treatments, targeting various types of cancer cells.
Used in Urological Applications:
Dicentrin functions as an alpha 1-adrenoceptor antagonist, making it effective against human hyperplastic prostates. This application highlights its potential use in the treatment of benign prostatic hyperplasia (BPH) and other related urological conditions.

Anti-cancer Activity

D-Dicentrine, a naturally occurring aporphine type isoquinoline alkaloid, isolated from the root of Lindera megaphylla Hemsl. (Lauraceae), was evaluated for its potential anti-cancer activity. Huang RL etc. found d-dicentrine significantly inhibited the growth of human hepatoma cell line HuH-7 by delaying its doubling time in tissue culture. An in vitro colony forming assay showed that d-dicentrine decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and MS-G2, used in our study.

InChI:InChI=1/C20H21NO4/c1-21-5-4-11-7-17-20(25-10-24-17)19-13-9-16(23-3)15(22-2)8-12(13)6-14(21)18(11)19/h7-9,14H,4-6,10H2,1-3H3

Synthetic route

(S)-methyl 10,11-dimethoxy-7a,8-dihydro-5H-[1,3]dioxolo[40,5’:4,5]benzo[1,2,3-de]benzo[g]quinoline-7(6H)-carboxylate → (S)-dicentrine (517-66-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	53%
With lithium aluminium tetrahydride In diethyl ether at 0℃;

demethyldicentrine (25394-59-6) + methyl iodide (74-88-4) → (S)-dicentrine (517-66-8)

diazomethane (186581-53-3, 908094-01-9) + formaldehyd (50-00-0) + litseferine (60142-18-9) → (S)-dicentrine (517-66-8)

Conditions	Yield
(i) HCO2H, (ii) /BRN= 102415/, MeOH, Et2O; Multistep reaction;

(7aS)-10,11-dimethoxy-7-methyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4',5':4,5]benzo[1,2,3-de]quinolin-5c-ol; hydrochloride (72203-90-8) → (S)-dicentrine (517-66-8)

Conditions	Yield
With hydrogenchloride; palladium on activated charcoal In acetic acid at 50 - 60℃; under 3102.9 Torr; for 4h;

(+-)-dicentrine → (S)-dicentrine (517-66-8)

Conditions	Yield
With D-tartaric acid; L-Tartaric acid

(6aS)-actinodaphnine (517-69-1) → (S)-dicentrine (517-66-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether; methanol View Scheme

3,4-methylenedioxyphenylethylamine (1484-85-1) → (S)-dicentrine (517-66-8)

Conditions

Yield

Multi-step reaction with 6 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 4 h / 0 - 20 °C / Inert atmosphere 2: trifluoromethylsulfonic anhydride; 2-chloropyridine / dichloromethane / 0.25 h / -78 - 0 °C / Inert atmosphere 3: triethylamine; formic acid; Noyori's catalyst / N,N-dimethyl-formamide / 24 h / 0 - 20 °C / Inert atmosphere 4: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 5: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 6: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

N-(2-(benzo[d] [1,3]dioxol-5-yl)ethyl)-2-(2-bromo-4,5-dimethoxyphenyl)acetamide (25829-00-9) → (S)-dicentrine (517-66-8)

Conditions

Yield

Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; 2-chloropyridine / dichloromethane / 0.25 h / -78 - 0 °C / Inert atmosphere 2: triethylamine; formic acid; Noyori's catalyst / N,N-dimethyl-formamide / 24 h / 0 - 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 4: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 5: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

(S)-5-(2-bromo-4,5-dimethoxybenzyl)-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline → (S)-dicentrine (517-66-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 2: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 3: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

5-(2-bromo-4,5-dimethoxy-benzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline (80041-80-1) → (S)-dicentrine (517-66-8)

Conditions

Yield

Multi-step reaction with 4 steps 1: triethylamine; formic acid; Noyori's catalyst / N,N-dimethyl-formamide / 24 h / 0 - 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 3: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 4: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

(S)-methyl 5-(2-bromo-4,5-dimethoxybenzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline-6(5H)-carboxylate → (S)-dicentrine (517-66-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

piperonal (120-57-0) → (S)-dicentrine (517-66-8)

Conditions

Yield

Multi-step reaction with 8 steps 1: acetic acid; ethylenediamine / 12 h / 70 °C / Molecular sieve; Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 12 h / 0 - 70 °C / Inert atmosphere 3: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 4 h / 0 - 20 °C / Inert atmosphere 4: trifluoromethylsulfonic anhydride; 2-chloropyridine / dichloromethane / 0.25 h / -78 - 0 °C / Inert atmosphere 5: triethylamine; formic acid; Noyori's catalyst / N,N-dimethyl-formamide / 24 h / 0 - 20 °C / Inert atmosphere 6: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 7: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 8: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

5-((E)-2-nitroethenyl)-1,3-benzodioxole (1485-00-3, 22568-48-5) → (S)-dicentrine (517-66-8)

Conditions

Yield

Multi-step reaction with 7 steps 1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 12 h / 0 - 70 °C / Inert atmosphere 2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 4 h / 0 - 20 °C / Inert atmosphere 3: trifluoromethylsulfonic anhydride; 2-chloropyridine / dichloromethane / 0.25 h / -78 - 0 °C / Inert atmosphere 4: triethylamine; formic acid; Noyori's catalyst / N,N-dimethyl-formamide / 24 h / 0 - 20 °C / Inert atmosphere 5: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 10 h / 20 °C / Inert atmosphere 6: palladium diacetate; potassium carbonate; di-tert-butyl(methyl)phosphonium tetrafluoroborate salt / N,N-dimethyl acetamide / 8 h / 130 °C / Inert atmosphere 7: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere View Scheme

(S)-dicentrine (517-66-8) → 7a,8-dehydrodicentrine (19843-03-9)

Conditions	Yield
With potassium permanganate

3,5-dihydroxyphenol (108-73-6) + sulfuric acid (7664-93-9) + (S)-dicentrine (517-66-8) → 5.6-dioxy-2.3-dimethoxy-aporphine

sodium acetate (127-09-3) + acetic anhydride (108-24-7) + (S)-dicentrine (517-66-8) → compound C22H23O5N

Upstream product

• 1485-00-3 5-((E)-2-nitroethenyl)-1,3-benzodioxole 
• 120-57-0 piperonal 
• 80041-80-1 5-(2-bromo-4,5-dimethoxy-benzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline 
• 25829-00-9 N-(2-(benzo[d] [1,3]dioxol-5-yl)ethyl)-2-(2-bromo-4,5-dimethoxyphenyl)acetamide 
• 1484-85-1 3,4-methylenedioxyphenylethylamine 
• 25394-59-6 demethyldicentrine 
• 74-88-4 methyl iodide 
• 517-69-1 (6aS)-actinodaphnine 
• 72203-90-8 (7aS)-10,11-dimethoxy-7-methyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4',5':4,5]benzo[1,2,3-de]quinolin-5c-ol; hydrochloride 
• 186581-53-3 diazomethane 
• 50-00-0 formaldehyd 
• 60142-18-9 litseferine 

Downstream Products

• 19843-03-9 Dehydrodicentrin 

Relevant academic research and scientific papers

Enantioselective synthesis and anti-parasitic properties of aporphine natural products

Chagas disease and visceral leishmaniasis are neglected protozoan diseases with significant impact in developing countries. Due to the limited number and toxicity of current therapies, new drug leads are urgently needed. In this work, four aporphine natural products were synthesized using an enantioselective, modular and convergent strategy, comprising eight steps in the longest linear sequence; key steps included Bischler-Napieralski cyclization/Noyori asymmetric reduction to construct the tetrahydroisoquinolines, and palladium-catalyzed arylation to close the C ring. Norglaucine, nordicentrine and dicentrine showed promising bioactivity against T. cruzi and L. infantum, suggesting potential for further development of these scaffolds as antiparasitic agents.

In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors

Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb?=?8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.

New aporphine alkaloids of Ocotea minarum

Fourteen aporphine alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea minarum Nees (Mez). The known alkaloids were identified through their physico-chemical properties as: leucoxylonine (VII), dicentrine (IV), ocoteine (V), leucoxine (VI), ocopodine (VIII), predicentrine (IX), dicentrinone (XIV) and thalicminine (XV). Six new aporphine alkaloids were also isolated: ocotominarine (I), ocominarine (III), nor-leucoxylonine (XI), iso-oconovine (XII), 4-hydroxydicentrine (XIII) and ocominarone (XVI). Their structures were determined using spectroscopic methods and chemical correlations.